ArticleLiterature Review

The effect of probiotics on functional constipation in adults: A systematic review and meta-analysis of randomized controlled trials

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Abstract

Background: Functional constipation is a prevalent, burdensome gastrointestinal disorder whose treatment remains challenging. Probiotics have been increasingly investigated in its management. Objective: The aim was to investigate the effect of probiotics on gut transit time, stool output, and constipation symptoms in adults with functional constipation via a systematic review and meta-analysis of randomized controlled trials (RCTs). Design: Studies were identified by searching 4 electronic databases, back-searching reference lists, contacting authors, and hand-searching abstracts. RCTs that reported administration of probiotics in adults with functional constipation were included. Two reviewers independently performed the screening, data extraction, and bias assessment. Outcome data were synthesized by using weighted mean differences (WMDs) or standardized mean differences (SMDs) with the use of a random-effects model. Results: A total of 660 records were identified of which 14 were eligible (1182 patients). Overall, probiotics significantly reduced whole gut transit time by 12.4 h (95% CI: -22.3, -2.5 h) and increased stool frequency by 1.3 bowel movements/wk (95% CI: 0.7, 1.9 bowel movements/wk), and this was significant for Bifidobacterium lactis (WMD: 1.5 bowel movements/wk; 95% CI: 0.7, 2.3 bowel movements/wk) but not for Lactobacillus casei Shirota (WMD: -0.2 bowel movements/wk; 95% CI: -0.8, 0.9 bowel movements/wk). Probiotics improved stool consistency (SMD: +0.55; 95% CI: 0.27, 0.82), and this was significant for B. lactis (SMD: +0.46; 95% CI: 0.08, 0.85) but not for L. casei Shirota (SMD: +0.26; 95% CI: -0.30, 0.82). No serious adverse events were reported. Attrition and reporting bias were high, whereas selection bias was unclear due to inadequate reporting. Conclusions: Probiotics may improve whole gut transit time, stool frequency, and stool consistency, with subgroup analysis indicating beneficial effects of B. lactis in particular. However, caution is needed with the interpretation of these data due to their high heterogeneity and risk of bias. Adequately powered RCTs are required to better determine the species or strains, doses, and duration of use of probiotics that are most efficacious.

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... The efficacy of probiotics as an alternative to alleviate constipation related symptoms vary, with high heterogeneity [28] in probiotics usage [29] and efficacy [30] , as well as in their impact on the intestinal microbiota composition [31] . Liu et al., systematically reviewed the efficacy of probiotics for functional constipation in children and concluded as no advocating use of probiotics in functional constipated children [32] . ...
... Specifically, consistent with earlier meta-analyses [28,29,52] , the current study found that supplementation of probiotics was effective in improving spontaneous bowel movements and stool consistency; however, the current study presents disagreement with these publications on the efficacy of probiotics of reducing gut transit time and QoL scores. In terms of constipation severity scores, probiotics supplementation was effective as in line with one study [4] , while contradicting to some several other studies [29,[53][54][55][56] . ...
... Specifically, consistent with earlier meta-analyses [28,29,52] , the current study found that supplementation of probiotics was effective in improving spontaneous bowel movements and stool consistency; however, the current study presents disagreement with these publications on the efficacy of probiotics of reducing gut transit time and QoL scores. In terms of constipation severity scores, probiotics supplementation was effective as in line with one study [4] , while contradicting to some several other studies [29,[53][54][55][56] . Notably, this inconsistency could be partly attributed to differences in study population and in study in-/ex-clusion criteria, for instance, the matrix of supplemented probiotics. ...
... Despite an increasing number of studies evaluating the impact of prebiotics, probiotics, and synbiotics on CC, their impact on constipation-related outcomes has so far been controversial due to the different regimens used [22,23]. This can be attributed to limited sample sizes, substantial heterogeneity, significant biases in individual studies, and limitations associated with the analytical methods employed [24]. ...
... Conversely, Schoot et al. and Zhang et al. reported a noteworthy surge in stool frequency with probiotic formulations, particularly emphasizing that Lactobacillus increased stool movements by 0.96 times per week [42,43]. Notably, Dimidi et al. observed a significant rise in stool frequency through probiotic use, specifically with Lactobacillus acidophilus and B. lactis, resulting in a substantial increase of 1.5 bowel movements per week [23]. This variance may be attributed to the inclusion of a greater number of trials with a significantly larger sample size in our study. ...
... The symbiotic relationship between probiotic microorganisms and prebiotic substrates fosters the colonization and activity of beneficial bacteria, potentially augmenting gut microbial diversity, bolstering intestinal barrier function, probiotics, while single-strain probiotics did not demonstrate notable effects [43]. Additionally, Dimidi et al.'s scrutiny of nine studies indicated an enhancement in stool consistency through the species-specific action of Lactobacillus acidophilus, but no distinct effect was observed for the L. casei Shirota strain [23]. In an RCT conducted by Chmielewska et al., the utilization of Lactobacillus acidophilus DN-173 010, Lactobacillus casei Shirota, and Escherichia coli Nissle 1917 exhibited positive effects on adult stool consistency [22]. ...
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Objective To compare the outcomes associated with the use of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults. Methods We searched eight electronic databases from database inception to July 11, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the treatment of chronic constipation. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of the evidence was assessed using the Confidence in Network Meta-Analysis framework. The analysis was conducted using R version 4.3.0. Results Out of the 37 RCTs, a total of 21 different types of interventions were reported, involving 3,903 patients. This NMA demonstrated that both prebiotics and synbiotics resulted in an increase in frequency of stool movements per week. Compared to placebo, lactulose (Mean difference [MD] = 3.39, 95% Confdence interval [CI] [1.13, 5.65], moderate certainty), mix2 (consisting of Lactulose and Bacillus coagulans) (MD = 3.63, 95% CI [1.37, 5.89], moderate certainty), mix6 (consisting of Lactulose and Bifidobacterium coagulans) (MD = 4.30, 95% CI [1.04, 7.54], low certainty), and mix7 (consisting of Lactulose, Bifidobacterium subtilis, and Enterococcus faecium) (MD = 4.58, 95% CI [1.35, 7.78], moderate certainty) exhibited a significant effect. Notably, mix7 demonstrated the highest probability of being the most effective intervention (94.8%). Furthermore, when compared to L. plantarum, four probiotics and two synbiotics showed significant advantages in the Patient Assessment of Constipation Symptoms (PAC-SYM) score. L. reuteri (MD = -13.74, 95% CI [-22.20, -4.66], very low certainty) exhibited a significant effect in improving the Patient Assessment of Constipation Quality of Life (PAC-QoL) score. In terms of safety, there were no statistically significant differences between the intervention and control groups in all adverse event analyses. Conclusions Moderate to very low evidence supports the use of lactulose and synbiotics to increase the number of weekly stool movements in patients, particularly highlighting the significant impact of synbiotics in increasing the number of weekly stool movements in patients with constipation. The use of L. paracasei showed improvements in PAC-SYM scores, while L. reuteri demonstrated enhancements in PAC-QoL scores.
... Probiotics are living microbes that benefit the host when ingested in sufficient quantities and are reported to improve defecation frequencies and treat constipation [1,2]. The effects of probiotics vary from person to person [3]. Individuals exhibiting significant effects of probiotics are called "responders" [4]; each responder exhibits a significant effect of a different probiotic. ...
... Blue and orange boxes represent the placebo and target probiotics periods, respectively. 1 , 2 , 3 , and 4 represent the start day index of the first capsule, the end day index of the first capsule, the start day index of the second capsule, and the end day index of the second capsule, respectively. and are the lag of effect start and end, respectively. ...
Article
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Recent advances in microbiome research have led to the further development of microbial interventions, such as probiotics and prebiotics, which are potential treatments for constipation. However, the effects of probiotics vary from person to person; therefore, the effectiveness of probiotics needs to be verified for each individual. Individuals showing significant effects of the target probiotic are called responders. A statistical model for the evaluation of responders was proposed in a previous study. However, the previous model does not consider the lag between intake and effect periods of the probiotic. It is expected that the lag exists when probiotics are administered and when they are effective. In this study, we propose a Bayesian statistical model to estimate the probability that a subject is a responder, by considering the lag between intake and effect periods. In synthetic dataset experiments, the proposed model was found to outperform the base model, which did not factor in the lag. Further, we found that the proposed model could distinguish responders showing large uncertainty in terms of the lag between intake and effect periods.
... A paucity of data did not allow us to conclude whether any particular probiotic is more effective than another. In terms of microbial alterations in adults, the analysis of the difference in efficacy of probiotic subgroups shows that B.lactis of Bifidobacterium can significantly improve the rectosigmoid transit time, defecation frequency, hard stools, flatulence in patients with chronic constipation, while L.casei Shirota of Lactobacillus has no obvious therapeutic effect (38,39). It is worth noting that the analysis of this research for different microbiota subgroups has high heterogeneity. ...
... In children, one recent study showed that in those with FC, the most discriminative species were Bacteroides fragilis, Bacteroides ovatus, Bifidobacterium longum, Parabacteroides species (increased), and Alistipes finegoldii (decreased) (44). Although research has found that probiotics do not significantly alleviate symptoms of FC in children, meta-analysis of adult FC patients has shown that probiotics treatment can effectively reduce the whole gut transit time and rectosigmoid transit time, increase defecation frequency, reduce difficulty with evacuation, bloating, abdominal pain or discomfort and hard stools (38). Therefore, we speculate that the difference in efficacy may be related to different (47)(48)(49). ...
Article
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Based on existing systematic reviews and meta-analyse we conducted this comprehensive review to evaluate the quality, effectiveness, and bias of evidence regarding the relationship between probiotic intake and improved constipation outcomes in children. A total of nine meta-analyses and systematic reviews were extracted from 628 articles, summarizing seven effectiveness indicators and the incidence of adverse reactions in the treatment of constipation. According to the results, our study revealed that the intake of probiotics in children with FC significantly improved treatment success rate and defecation frequency, while decreased the recurrence rate of constipation. However, no significant association was detected between probiotics intake and frequency of abdominal pain, stool consistency, frequency of defecation pain, frequency of fecal incontinence of children with FC. The intake of probiotics did not increase the incidence of adverse reactions and demonstrated good safety.
... Probiotics are live microorganisms that, when consumed in appropriate amounts, provide health benefits [1] . They have been reported to boost the digestive [2] and immune systems [3] , and improve skin conditions [4] . The awareness of probiotics' benefits, coupled with increasing consumers' interest in preventive healthcare, has propelled the demand for probiotic products, leading to the expansion of the probiotic industry [5] . ...
... In order to provide the broader healthcare community with a reliable probiotic reference, this study aims to improve the quality, user-friendliness and usefulness/applicability of the database. Therefore, the following objectives were established: (1) to update the database with studies published after 2019 and with more probiotic products; (2) to enhance the database by improving its existing features and introducing new features; and (3) to perform an evaluation of the enhanced database from the three aspects mentioned above by conducting a pilot survey involving the local pharmacist community. ...
Article
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A probiotics practice reference database (https://bit.ly/sg-probiotics-ref) compiling probiotic products and clinical evidence on probiotics’ efficacy was previously developed to help healthcare professionals (HCPs) in making appropriate probiotic recommendations. This database has been enhanced and updated to contain published clinical studies after 2019 and probiotic products from multiple retail stores. A further 275 study excerpts and 304 products were newly added, thus resulting in the updated database containing a total of 859 study excerpts, 753 products and 5708 product-study links. The database was also enhanced with new features to improve search flexibility. A pilot evaluation of the database among 25 hospital and community pharmacists showed that the majority agreed that the database provided complete, comprehensive and relevant information on probiotic products and indications (72–92%), was useful and applicable to local practice (64–88%) and was user-friendly (92–100%). In addition, most indicated that they would recommend the database to others and continue to use it for probiotics information (96% each). Our findings showed potential in the database being used as an evidence-based resource for HCPs practice. Future work will aim to expand on and validate the database content, as well as evaluate its application among other groups of HCPs.
... Non-pharmacological interventions, such as probiotics, synbiotics, increased water intake, dry cupping, and additional biofeedback or behavioral therapy, have shown promise as effective and safe approaches to treat FC in children; however, further research is necessary to fully explore the utility of probiotics in alleviating FC symptoms in patients of all ages [22]. A recent systematic review and meta-analysis concluded that probiotics may improve overall intestinal transit time and defecation frequency in adults with FC, despite a large amount of heterogeneity among studies [23]. The consumption of probiotics, particularly multispecies probiotics, may lead to a notable reduction in gut transit time, increased stool frequency, and improved stool consistency [24]. ...
... Consistent with our findings, a meta-analysis demonstrated that probiotic (Bifidobacterium and L. plantarum) interventions were significantly superior to a placebo in the treatment of FC, showing improved efficacy and reducing the recurrence rate of constipation, thereby enhancing clinical effectiveness [23]. Regarding safety, the introduction of combined medication appeared to reduce adverse reactions in individuals who received this treatment compared to the control group. ...
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Aim To analyze the efficacy and safety of Bifidobacterium quadruple viable tablets combined with mosapride citrate for the treatment of constipation. Methods A systematic review was performed on studies published until July 2022 in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang. The efficacy rate, adverse reaction rate, recurrence rate, and clinical symptoms were included in the measured outcomes. Results The efficacy of Bifidobacterium quadruple viable tablets combined with mosapride citrate in the treatment of constipation was higher than that of mosapride citrate alone (OR = 4.75, 95% CI (3.27, 6.90), Z = 8.19, P < 0.001; I² = 0.0%, P = 0.645). There was no significant difference in the incidence of adverse reactions between the two groups (OR = 0.97, 95% CI (0.61,1.57), Z = 0.11, P = 0.911; I² = 0.0%, P = 0.958). The recurrence rate of constipation in patients receiving the combination treatment was lower than that of patients treated with mosapride citrate alone (OR = 0.48, 95%CI (0.31, 0.73), Z = 3.38, P = 0.001; I² = 29.8%, P = 0.200). Conclusions Bifidobacterium quadruple viable tablets combined with mosapride citrate demonstrated efficacy and safety in treating constipation. Probiotics have the potential to positively influence gut health and microbial profiles in patients with functional constipation.
... To the best of our knowledge, this is the first meta-analysis to summarize the available RCTs data regarding constipation and probiotics in older people. Some researchers performed meta-analyses in adults and children, but no meta-analysis has investigated the effects of probiotics on constipation in elderly people [45][46][47][48]. ...
... The results of this meta-analysis reveal that probiotic supplementation significantly improved the frequency of defecation, specifically with single-strain supplementation and in long-term consumption of probiotics in elderly. The positive effects of probiotics on stool frequency in constipated adults were also reported in a meta-analysis [45]. However, a systematic review reported that probiotic interventions did not influence defecation frequency in children [53]. ...
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Cognitive decline and constipation are common complications in the elderly. Probiotics are potential therapeutic agents to ameliorate cognitive impairment through gut-brain axis. Several clinical studies have investigated the beneficial effects of probiotics on cognitive impairment and constipation in elderly. However, a quantitative meta-analysis is required to evaluate the efficacy of probiotics on cognitive function and constipation. Thirteen clinical studies were included in this meta-analysis. We examined the risk of bias assessment and heterogeneity of eight studies for cognition and five studies for constipation, followed by group and subgroup meta-analyses using a random-effects model to evaluate the potential of probiotic supplements on cognition function and constipation in aged people. The results of the pooled meta-analysis revealed that probiotic supplementation did not improve the cognitive rating scale assessment for all studies (estimate = 0.13; 95%CI [-0.18, 0.43]; p = 0.41; I2 = 83.51%). However, subgroup analysis of single strain supplementation showed improved cognitive function in elderly people (estimate = 0.35; 95%CI [0.02, 0.69]; p = 0.039; I2 = 19.19%) compared to multiple strains. Probiotics also enhanced defecation frequency in constipated patients (estimate = 0.27; 95%CI [0.05, 0.5]; p = 0.019; I2 = 67.37%). Furthermore, probiotic supplementation resulted in higher fecal Lactobacillus counts than placebo (estimate = 0.37; 95%CI [0.05, 0.69]; p = 0.026; I2 = 21.3%). Subgroup analysis indicated that a probiotic intervention period of ≥4 weeks was more effective (estimate = 0.35; 95%CI [0.01, 0.68]; p = 0.044; I2 = 0%) in reducing constipation symptoms than a short intervention duration. Based on these results, probiotic supplementation could be a potential intervention to reduce constipation symptoms in the elderly population. The heterogeneity between studies is high, and limited trials are available to evaluate the cognitive function of aged individuals using probiotics. Therefore, further studies are required to determine the effect of probiotics on cognition.
... 15,16 Sin embargo, sí existe diferencia estadísticamente significativa ante el grupo control, por lo que es imprescindible utilizar un adyuvante en el RAR, 17 citando nuevamente a Araujo y colaboradores, donde en su investigación del año 2022 9 sugieren su uso, ya que existen recidivas especialmente donde los instrumentos manuales y ultrasónicos no alcanzan a llegar 18 a todos los sitios colonizados por bacterias, 19 por lo que habrá recolonización. 9,20 Cabe destacar que aunque no fue el propósito de este estudio, basados en los resultados obtenidos, se encontró diferencia estadísticamente significativa en la disminución de placa dentobacteriana (biofilm) (PDB) y sangrado al sondeo (SAS), en los grupos probióticos y antibióticos, 21 tal como se demostró en estudios realizados por Ramos y colaboradores en el año 2022 22 y un año después en el estudio realizado por de Almeida y su equipo en el año 2023, 23 mientras que el grupo control que no recibió tratamiento adyuvante 24,25 no obtuvo disminución significativa de los parámetros mencionados, 7 semejante a los resultados que se registraron en el estudio de Zandbergen y su grupo, donde refieren que el RAR solo no es suficiente para erradicar por completo la compleja organización y estructura de patógenos periodontales. 26 Esta investigación se realizó basada en los estudios realizados por los autores ya citados, 27,28 y otros tales como Faveri y colaboradores 29 y Feres y su equipo 30 siguiendo el mismo protocolo, se tomaron como medida el SAS inicial 31,32 donde todos los pacientes presentaron ...
... One of the personalized therapeutic interventions is microbiota-directed therapy. Bifidobacterium longum BB536 shows improvement in weekly spontaneous bowel movements versus placebo (p < 0.01) in methane-positive constipation [30][31][32]. Fecal microbiota transplantation (FMT) from high-butyrate producers (>18 µmol/g) demonstrates superior efficacy in restoring motility [33]. Another is brain-gut axis modulation. ...
Article
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Background: The composition and metabolic activity of the gut microbiota play a crucial role in various health conditions, including the occurrence and development of chronic constipation. Recent metabolomic advances reveal that gut microbiota-derived metabolites—such as SCFAs, bile acids, neurotransmitters, and microbial gases—play critical roles in regulating intestinal function. Methods: We systematically analyzed the current literature on microbial metabolomics in chronic constipation. This review consolidates findings from high-throughput metabolomic techniques (GC-MS, LC-MS, NMR) comparing metabolic profiles of constipated patients with healthy individuals. It also examines diagnostic improvements and personalized treatments, including fecal microbiota transplantation and neuromodulation, guided by these metabolomic insights. Results: This review shows that reduced SCFA levels impair intestinal motility and promote inflammation. An altered bile acid metabolism—with decreased secondary bile acids like deoxycholic acid—disrupts receptor-mediated signaling, further affecting motility. Additionally, imbalances in amino acid metabolism and neurotransmitter production contribute to neuromuscular dysfunction, while variations in microbial gas production (e.g., methane vs. hydrogen) further modulate gut transit. Conclusions: Integrating metabolomics with gut microbiota research clarifies how specific microbial metabolites regulate gut function. These insights offer promising directions for precision diagnostics and targeted therapies to restore microbial balance and improve intestinal motility.
... Additionally, severe constipation may result in dangerous physical symptoms such as fainting and may predispose individuals to the development of rectal cancer [6], colon cancer, and cardiovascular disease [7]. In recent years, an increasing number of studies have recognized that the pathogenesis of constipation is highly complex, involving multiple factors throughout the gastrointestinal tract, such as gastrointestinal motility, hormone secretion, microecological balance, metabolite alterations, and barrier function [8,9]. The etiology of constipation is varied, encompassing insufficient hydration/fiber consumption, and aberrant bowel function, decreased physical activity, and underlying medical conditions [10,11]. ...
Article
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Functional constipation ranks among the most common disorders impacting human health, which is manifested by difficulty in defecation and a complex etiology. L-Arabinose, a pentose found naturally in fruit rinds and cereal husks, has been reported to regulate glycolipid metabolism, improve glucose homeostasis, and exhibit anti-inflammatory effects. However, the effect and precise mechanism of L-Arabinose on functional constipation remain unclear. In this study, the effect of L-Arabinose in alleviating functional constipation induced by diphenoxylate was evaluated. The model group consisted of functional constipation mice that did not receive any intervention. The positive drug group was treated with 2.0 g/kg lactulose, while the intervention group was given 0.5 g/kg, 0.75 g/kg, 1.0 g/kg, and 2.0 g/kg L-Arabinose, respectively. The data suggested that 20 days of L-Arabinose intervention could shorten the first black stool defecation time, increase fecal water content, and enhance the rate of small intestinal propulsion in mice with functional constipation induced by diphenoxylate. Additionally, L-Arabinose reversed the protein expression of functional constipation-related intestinal factors in the colon, characterized by a decrease in the expression of water channel proteins AQP3 and AQP4, as well as an increase in the expression of tight-junction proteins ZO-1, Claudin-1 and Occludin. Furthermore, L-Arabinose modulated the levels of hormones (MTL, Gas) and neurotransmitters (5-HT, VIP) related to the digestive systems of mice with constipation, resulting in elevated levels of 5-HT, MTL, and Gas and decreasing levels of VIP. Histopathological analysis also revealed that L-Arabinose intervention improved the intestinal inflammatory response. Furthermore, 16S rRNA sequencing and metabolomics of the intestinal microbiota demonstrated that L-Arabinose treatment improved both the intestinal microbiota composition and the metabolite levels. This study suggests that L-Arabinose can serve as a potential functional ingredient to promote intestinal health, enhance gastrointestinal motility and barrier function, regulate osmotic pressure, restore neurotransmitter levels, and effectively relieve functional constipation.
... Probiotics, defined as live microorganisms that confer health benefits to the host when administered in adequate amounts, have drawn considerable attention for their potential role in alleviating intestinal constipation [23]. The therapeutic mechanism of probiotics in constipation includes their ability to modulate gut microbiota composition, enhance gut motility, increase short-chain fatty acid (SCFA) production, and reduce local inflammation [24]. Probiotics such as Bifidobacterium, Lactobacillus, and Saccharomyces boulardii have been studied in various randomized controlled trials (RCTs) for their efficacy in treating constipation and improving patients' quality of life [25][26][27]. ...
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Introduction Intestinal constipation is a substantive global health concern, significantly impairing patient quality of life. An emerging view is that the gut microbiota plays a critical role in intestinal function, and probiotics could offer therapeutic benefits. This study aims to consolidate evidence from randomized controlled trials (RCTs) that assess the effectiveness of probiotics in modulating microbiota and ameliorating symptoms of constipation. Methods We will execute a systematic evidence search across Medline (via PubMed), Embase, Cochrane CENTRAL, Web of Science, Scopus, and CINAHL, employing explicit search terms and further reference exploration. Two independent reviewers will ensure study selection and data integrity while assessing methodological quality via the Cochrane Collaboration’s Risk of Bias-2 tool. Our primary goal is to outline changes in microbiota composition, with secondary outcomes addressing symptom relief and stool characteristics. Meta-analyses will adopt a random-effects model to quantify the effects of interventions, supplemented by subgroup analyses and publication bias assessments to fortify the rigor of our findings. Discussion This study endeavors to provide a rigorous, synthesized overview of the probiotics interventions evidence for modulating gut microbiota in individuals with intestinal constipation. The insights derived could inform clinical guidelines, nurture the creation of novel constipation management strategies, and direct future research in this field. Ethics and dissemination As this study aggregates and analyzes existing data without direct human subject involvement, no ethical approval is required. We will disseminate the study’s findings through scientific forums and seek publication in well-regarded, peer-reviewed journals. Trial registration OSF registration number: 10.17605/OSF.IO/MEAHT.
... A meta-analysis evaluating randomized controlled trials concluded that Bifidobacterium lactis intake reduced transit time in patients with chronic constipation [58,66,67,85,86]. A 2022 meta-analysis by Zhang et al. involving 43 clinical trials with 5.531 IBS patients suggested that Bifidobacterium coagulans is highly effective as a therapeutic agent for IBS-D patients, enhancing symptoms and quality of life [68]. ...
Article
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Irritable bowel syndrome is a common functional gastrointestinal disorder characterized by recurrent abdominal discomfort, bloating, cramping, flatulence, and changes in bowel movements. The pathophysiology of IBS involves a complex interaction between motor, sensory, microbiological, immunological, and psychological factors. Diversity, stability, and metabolic activity of the gut microbiota are frequently altered in IBS, thus leading to a situation of gut dysbiosis. Therefore, the use of probiotics and probiotic-derived metabolites may be helpful in balancing the gut microbiota and alleviating irritable bowel syndrome symptoms. This review aimed to report and consolidate recent progress in understanding the role of gut dysbiosis in the pathophysiology of IBS, as well as the current studies that have focused on the use of probiotics and their metabolites, providing a foundation for their potential beneficial effects as a complementary and alternative therapeutic strategy for this condition due to the current absence of effective and safe treatments.
... In this context, probiotics, which are live microorganisms that confer health benefits when administered adequately, play a crucial role [1]. Probiotic supplementation has the potential to alleviate digestive discomfort [2], improve electrolyte absorption [3], and facilitate essential amino acid and vitamin absorption in the intestine [4,5]. However, fully realizing this potential remains difficult, in part due to the unavoidable loss in viability as probiotics traverse through the challenging stomach environment. ...
Article
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The ability of probiotics, comprising live microbiota, to modulate the composition of intestinal microbiomes has been connected to modulation of the central nervous system (Gut–Brain axis), neuroendocrine system (Gut–Skin axis), and immune response (Gut–Immune axis). Less information is known regarding the ability of postbiotics (cell wall components and secreted metabolites derived from live organisms) to regulate host immunity. In the present study, we tested postbiotics comprising single strains of bacteria and yeast (Lactobacillus acidophilus 16axg, Lacticaseibacillus rhamnosus 18fx, Saccharomyces cerevisiae var. boulardii 16mxg) as well as combinations of multiple strains for their ability to stimulate cytokine production by human CD14⁺ monocytes. We quantified cytokine gene and protein expression levels in monocytes following stimulation with postbiotics. Both heat-killed L. acidophilus and L. rhamnosus stimulated naïve monocytes without significant differences between them. Heat-killed S. boulardii stimulated less cytokine production compared to postbiotic bacteria at the same concentration. Interestingly, the addition of heat-killed yeast to heat-killed L. acidophilus and L. rhamnosus resulted in an enhancement of immune stimulation. Thus, heat-killed postbiotics have immune-modulating potential, particularly when bacteria and yeast are combined. This approach may hold promise for developing targeted interventions that can be fine-tuned to modulate host immune response with beneficial health impact.
... The benefits of probiotic strains and their combinations have been evaluated extensively. The clinical significance of probiotics is mainly indicated by their roles in metabolic disorders (e.g., obesity and diabetes) [2,3], gastrointestinal disorders (e.g., antibiotic-associated diarrhea and constipation) [4,5], depression, anxiety, and mental disorders [6]. ...
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In this study, the probiotic yeast Saccharomyces boulardii was engineered to secrete the antiviral lectin griffithsin. Twelve genetic tools with the griffithsin gene were cloned into the vector pSF-TEF1-URA3 and introduced into S. boulardii. In the recombinant strains, a 16.9 kDa band was detected using SDS-PAGE and further recognized by griffithsin antibody with Western blotting. S. boulardii strains FM, FT, HC, and HE with a high yield of griffithsin were acquired for property characterization in vitro. The four recombinant strains displayed a similar growth pattern to that of the control strains, while their morphological characteristics had changed according to scanning electron microscopy. In simulated gastrointestinal digestive fluids, the survival rates of S. boulardii FM, FT, and HC were significantly decreased (86.32 ± 1.49% to 95.36 ± 1.94%) compared with those of the control strains, with survival rates between 95.88 ± 0.00% and 98.74 ± 1.97%. The hydrophobicity of S. boulardii FM, the strain with the highest griffithsin production, was significantly increased to 21.89 ± 1.07%, and it exhibited a reduced auto-aggregation rate (57.64 ± 2.61%). Finally, Vero cells infected with porcine epidemic diarrhea virus (PEDV) were used to evaluate the strains’ antiviral activity, and the rate at which S. boulardii FM inhibited PEDV reached 131.36 ± 1.06%, which was significantly higher than that of the control group.
... Additionally, probiotics, such as Escherichia coli have shown positive effects in maintaining remission in ulcerative colitis [50]. Probiotics also offer benefits in relieving constipation and can serve as an adjunct therapy in eradicating Helicobacter pylori infections [51,52]. ...
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Probiotics are live microorganisms that, when given in sufficient quantities, offer health benefits, and are essential for preserving the gut health and general well-being of humans. Probiotics have a wide range of beneficial impacts on human health, which include immunomodulation, improved gut barrier function, and competitive exclusion of pathogens. Research indicated that probiotics can help to lower the cholesterol levels and prevent and treat several illnesses, including cancer, lactose intolerance, irritable bowel syndrome, anemia, obesity, and allergy disorders. Probiotics also have a major impact on the composition of the gut microbiota, which helps to restore microbial balance and increase the number of beneficial bacteria. Probiotics due to their capacity to modulate the immune system and reduce inflammation have shown encouraging results when given as a supportive therapy to the patients during COVID-19. Probiotics are now easily available commercially worldwide as people are more frequently using for getting positive health benefits. Probiotics can be taken either in drink of dairy products or into foods or even can be consumed as supplements. Probiotic therapeutic applications will be further optimized as research progresses and the specific strains and formulations that maximize health benefits are understood. This review highlights the emerging role of probiotics in enhancing human health.
... Indeed, micronutrients such as polyphenols can from constipation by Riezzo et al. [175], demonstrated the functional benefits of the probiotic enriched vegetable food in reducing constipation symptoms. This study is the only in vivo study employing a plant-based probiotic food included in the systematic review and meta-analysis by Dimidi et al. [177], which aimed to investigate the effect of probiotics on functional constipation in adults. No adverse events were reported in either the probiotic or the placebo group, and > 95% compliance was achieved with the probiotic-containing artichokes, confirming that the probiotic addition did not affect the sensory quality of the product. ...
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The Mediterranean Diet (MedDiet) is a widely recognized dietary pattern, with its effects largely attributed to “functional foods” which are able to positively influence one or more target functions, improving health and maintaining a state of well-being. In this review, three “case-study” typical of the MedDiet, such as artichokes, capers and table olives are considered as traditional functional vegetables rich in bioactive compounds, mainly polyphenols. The review extensively discusses the antioxidant effects of these molecules, as well as their role in aging prevention and reduction, maintaining human health, and influencing the abundance and composition of intestinal microbiota. Additionally, this review focuses on the fate of the dietary polyphenols along the digestive tract. Among biotechnological strategies, the review explores the role of fermentation process in modifying the biochemical profile, recovery, bioaccessibility and bioavailability of bioactive compounds present in some vegetable foods of MedDiet. Finally, the main challenges in the selection, addition, and maintenance of probiotic strains in traditional food products are also summarized, with a view to develop new probiotic carriers for “functional diets”.
... Recent studies have elucidated the signi cance of gastrointestinal microbiota in the regulation of gut motility and constipation. A systematic review and meta-analysis of RCTs demonstrated that probiotics were associated with a signi cant reduction in whole gut transit time and an increase in stool frequency 24 . Furthermore, FMT has been shown to modulate intestinal microecology and alleviate symptoms in individuals suffering from constipation 25 . ...
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Background Globally, functional constipation (FC) is a significant health problem. Therefore, greater understanding of the modifiable risk factors is needed to develop effective treatment and preventive strategies. The presence of depression symptoms (DS), anxiety symptoms (AS), and Bacteroides stercoris abundance in stool (BSAIS) has been found to be correlated with FC based on the previous observational study. Nevertheless, the causal relationship between these factors and FC remains uncertain due to observational study limitations. Methods Mendelian randomization (MR) leverages genetic variants as instrumental variables (IVs), exploiting genetically determined variability to evaluate causal relationships. In this two-sample MR analysis, genetic data were obtained from separate cohorts with DS AS, BSAIS, and FC. Genome-wide association studies (GWAS) identified genetic variants associated with DS, AS, BSAIS, and FC, which were utilized as IVs to infer causality.The study utilized bidirectional MR analysis to examine the influence of DS AS, and BSAIS on the risk of FC, as well as the potential for reverse causation. Subsequently, sensitivity tests including MR Egger, Inverse variance weighted (IVW), and MR-egger_intercept were performed to evaluate heterogeneity and pleiotropy in the IVs, thereby providing a reliable and confident estimation of the causal effect. Results Utilizing bidirectional two-sample MR analysis, we investigated the potential causal associations between DS, AS, BSAIS, and FC using data from the IEU open GWAS database. Our analysis, based on the IVW method of two-sample MR analysis, revealed significant causal effects of DS (odds ratio [OR] = 1.122, 95% confidence interval [CI]: 1.031-1.221, P = 0.008), AS (OR = 1.129, 95% CI: 1.037-1.230, P = 0.005), and BSAIS (OR = 1.137, 95% CI: 1.048-1.233, P = 0.002) on FC. Furthermore, we observed reverse causal effects of FC on DS (OR = 1.156, 95% CI: 1.048-1.275, P = 0.004) and AS (OR = 1.164, 95% CI: 1.057-1.281, P = 0.002). Sensitivity analyses did not reveal any evidence of heterogeneity or pleiotropy in the IVs, as indicated by P values exceeding 0.05. Conclusion This study suggests a potential causal relationship between DS, AS, BSAIS, and FC, along with the presence of reverse causality. No heterogeneity or pleiotropy were revealed by sensitivity tests, making these findings reliable and confident. The mitigation of symptoms of depression and anxiety and manipulation of gastrointestinal microbiota composition may potentially ameliorate symptoms of FC, and vice versa.
... In other words, alleviating constipation is important not only from the perspective of health issues but also from the perspective of solving social issues. Fermented milk, one of the oldest probiotics, is often reported to be associated with reduced constipation [7]. Recent studies have shown that fermented milk has beneficial effects not only in reducing constipation, but also in modification of gut microbiota and many other aspects of physical health [8][9][10][11]. ...
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Probiotic-fermented milk is commonly used to maintain intestinal health. However, the effects of heat-treated fermented milk, which does not contain live microorganisms, on intestinal function are not yet fully understood. This study aimed to investigate whether heat-treated Lactobacillus helveticus CP790-fermented milk affects fecal microbiota and gut health as a “postbiotic”. A randomized, double-blind, placebo-controlled trial was conducted in healthy Japanese individuals aged 20–59 years with a tendency toward constipation. Participants consumed 100 mL of either the test beverage (n = 60) or placebo beverage (n = 60) for four weeks. The test beverages were prepared with heat-treated CP790-fermented milk, while the placebo beverages were prepared with nonfermented milk flavored with lactic acid. Fecal samples were analyzed using 16S rRNA gene sequencing. Constipation symptoms were assessed using defecation logs and the Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire. Mood state was also assessed using the Profile of Mood States 2 (POMS2) questionnaire to explore its potential as a “psychobiotic”. Desulfobacterota were significantly decreased by CP790-fermented milk intake. PICRUSt2 analysis predicted a decrease in the proportion of genes involved in the sulfate reduction pathway following the consumption of CP790-fermented milk. The CP790-fermented milk intervention significantly improved stool consistency and straining during defecation. These improvements were correlated with a decrease in Desulfobacterota. After the intervention, overall mood, expressed as total mood disturbance, and depression–dejection were significantly better in the CP790 group than in the placebo group. These results suggest that the intake of CP790-fermented milk could be effective in modulating gut microbiota and improving constipation symptoms and mood states.
... К настоящему времени выполнено достаточно большое количество клинических исследований, в которых тестировали эффективность различных пробиотических препаратов при ФЗ. Несмотря на отличия в степени выраженности терапевтического эффекта, в целом в этих работах показано, что применение пробиотиков приводит к уменьшению времени кишечного транзита, увеличению частоты дефекации и улучшению характеристик стула [68,69,70]. Результаты мета-анализа 2020 г. свидетельствуют о том, что более выраженной клинической эффективностью обладают мультикомпонентные пробиотические препараты, которые включают несколько штаммов, а не изолированные штаммы бифидобактерий [71]. ...
Article
The main link in the pathogenesis of functional constipation (FC) with slow intestinal transit is a decrease in the motor function of the colon. Data from experimental and clinical studies indicate that the gut microbiota is involved in the regulation of colonic motility through various mechanisms. At the same time, the study of the molecular processes underlying the influence of the intestinal microbiota and its metabolites on the motor function of the colon is at an early stage. The review analyzes the literature on the role of intestinal microbiota in the development of FD, presents data on the mechanisms of action of various microbial metabolites on the motor and secretory function of the colon, and briefly describes new approaches to the treatment of FD based on modulating the composition of the intestinal microflora. FZ is accompanied by specific changes in the composition of the intestinal microbiota, and in recent years, researchers have established cause-and-effect relationships between certain enterotypes and the development of FZ. To date, the main microbial metabolites have been identified that have a stimulating or inhibitory effect on propulsive peristalsis, as well as on the intensity of secretion of anions and water by colonocytes. Approaches to optimizing the composition of the microbiota in FZ are based on the use of pro- and prebiotics, antibiotics, as well as the use of intestinal microbiota transplantation. A deeper understanding of the molecular mechanisms mediating the influence of the microbiota and its metabolites on colonic motor function may serve as the basis for the development of new approaches to the treatment of FZ.
... Our data with LES activity has indicated the preventive and therapeutic effects on LES activity. Third, some probiotics increase the production of lactate and short-chain fatty acids reducing luminal pH, which, as some researchers have proposed, may enhance colonic peristalsis and shorten whole gut transit time [31]. In the Figs. ...
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Probiotic Bacillus coagulans TCI803 (BC) may have impact on gastrointestinal protection. This study was designed to investigate the effects of BC on Helicobacter pylori ( H. pylori ) induced gastric inflammation in mice and acid-induced lower esophageal sphincter (LES) dysfunction in rat. We determined the oxidative stress/apoptosis/autophagy signaling pathway in H. pylori -induced gastric inflammation and HCl-evoked LES inflammation. H. pylori increased leukocyte infiltration mediated inflammation and gastric cytokines array, 3NT/4HNE-mediated oxidative stress and Bax/Caspase 3-mediated apoptosis, but decreased Beclin-1/LC3-II-mediated autophagy in the mice gastric mucosa. BC treatment decreased inflammation, cytokines release, oxidative stress and apoptosis and reversed autophagy in H. pylori infected gastric mucosa. Esophageal infusion of saline evoked an increase of LES pressure and efferent vagus nerve activity during the emptying phase, however, esophageal infusion of HCl dysregulated LES motility by a decrease in threshold pressure, intercontraction interval and an increase in efferent vagus nerve activity. BC treatment significantly recovered the level of threshold pressure, intercontraction interval and depressed the enhanced efferent vagus nerve activity. In vitro LES wire myography data displayed that HCl treated LES significantly decreased the contractile response to acetylcholine. BC treatment significantly restored the contractile response to acetylcholine in LES wire myography. LES after HCl stimulation significantly increased leukocyte infiltration-mediated inflammation, whereas BC treatment effectively reduced the leukocyte infiltration-mediated inflammation in the HCl treated LES. In summary, we suggest that BC via anti-oxidation and anti-inflammation confers gastroesophageal protection against H. pylori involved oxidative stress/inflammation/apoptosis/autophagy signaling in mice with gastric inflammation and HCl induced LES dysregulation and inflammation.
... In cases with a disturbance in the content of intestinal flora, probiotics can be suggested as a supportive treatment (11). Moreover, improvement in constipation symptoms, including softening the stool, increasing colonic transit, and subsequently, more frequent defecation, have been observed after probiotics administration (12). Prebiotics, which are indigestible compounds, serve as food for probiotics. ...
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Background: Changes in the intestinal microbial flora may contribute to the occurrence and intensification of functional constipation (FC). Probiotics have shown promise as a potential alternative treatment for constipation. Objectives: The main goal of this study is to assess the effects of an Iranian multispecies synbiotic supplement on FC. Methods: This randomized controlled trial (RCT) recruited 115 adult patients who met the Rome IV criteria for FC after fulfilling the inclusion criteria. They were randomly assigned to receive either psyllium (n = 57) or psyllium plus synbiotic (n = 58) daily for 4 weeks. The treatment response was evaluated based on changes in stool consistency (based on the Bristol scale), bloating severity, and constipation intensity (based on the Wexner Constipation Scoring System), and those with a partial to excellent response were considered treatment successes. Results: The two groups did not differ in terms of sex, age, and BMI. The downward trend of stool consistency, bloating, as well as, constipation intensity was significant after 2 weeks of synbiotic-containing intervention. Treatment success after 4 weeks was 75.44% in the synbiotic group, compared to 30.91% in the psyllium-alone group (P < 0.001), indicating the superior efficiency of the synbiotic. Neither treatment exhibited adverse effects (P = 0.924), although psyllium was found to be less tolerable than the synbiotic (P = 0.026). Conclusions: Multispecies synbiotic intake for 4 weeks may be a promising treatment option for FC, given its striking favorable effects on constipation severity, safety, and tolerability.
... The proposed mechanisms of benefit in constipation include the restoration of non-pathogenic gastrointestinal microbiota and the increased bacterial production of lactate and short-chain fatty acids. For STC, their effectiveness is similarly unclear, though a 2014 meta-analysis by Dimidi et al., investigating the effects of probiotics in patients with functional constipation, showed a significantly improved whole gut transit time, stool frequency, and stool consistency; however, there was significant heterogeneity between the studies and the high risk of bias, and the outcomes in patients with STC were not observed [34]. ...
Article
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Slow transit constipation (STC) has an estimated prevalence of 2–4% of the general population, and although it is the least prevalent of the chronic constipation phenotypes, it more commonly causes refractory symptoms and is associated with significant psychosocial stress, poor quality of life, and high healthcare costs. This review provides an overview of the pathophysiology, diagnosis, and management options in STC. STC occurs due to colonic dysmotility and is thought to be a neuromuscular disorder of the colon. Several pathophysiologic features have been observed in STC, including reduced contractions on manometry, delayed emptying on transit studies, reduced numbers of interstitial cells of Cajal on histology, and reduced amounts of excitatory neurotransmitters within myenteric plexuses. The underlying aetiology is uncertain, but autoimmune and hormonal mechanisms have been hypothesised. Diagnosing STC may be challenging, and there is substantial overlap with the other clinical constipation phenotypes. Prior to making a diagnosis of STC, other primary constipation phenotypes and secondary causes of constipation need to be ruled out. An assessment of colonic transit time is required for the diagnosis and can be performed by a number of different methods. There are several different management options for constipation, including lifestyle, dietary, pharmacologic, interventional, and surgical. The effectiveness of the available therapies in STC differs from that of the other constipation phenotypes, and prokinetics often make up the mainstay for those who fail standard laxatives. There are few available management options for patients with medically refractory STC, but patients may respond well to surgical intervention. STC is a common condition associated with a significant burden of disease. It can present a clinical challenge, but a structured approach to the diagnosis and management can be of great value to the clinician. There are many therapeutic options available, with some having more benefits than others.
... Such a high number of bacterial cells should persist throughout the shelf life of food. Probiotic cells must survive the passage through the gastrointestinal tract, reach the colon in sufficient numbers, and, finally, adhere to, and colonize the gut epithelium [148][149][150]. ...
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Lactic acid fermentation is one of the oldest and most commonly used methods of bioconservation. This process is widely used for food preservation and also for a production technique that relies on the metabolism of lactic acid bacteria (LAB) to convert carbohydrates into lactic acid. This fermentation imparts unique flavors and texture of foods, extends their shelf life, and can offer health benefits. There are both traditional and new microorganisms involved in the lactic acid fermentation of food. The current review outlines the issues of fermented foods. Based on traditional fermentation methods, a broad panorama of various food products is presented, with the microorganisms involved. The methods of both traditional fermentation (spontaneous and back-slopping) as well as the importance and application of starter cultures in mass food production are presented. Currently, based on the results of scientific research, the health-promoting effect of fermented foods is becoming more and more important. This is due to the presence of probiotic microorganisms that are naturally presented or may be added to them, as starter cultures or additives, and from the presence of prebiotics and postbiotics. New innovative methods of using probiotic microorganisms open up new and broad perspectives for fermented functional foods.
... A meta-analysis investigating randomized controlled trials concluded that administration of Bifidobacterium lactis decreased transit time in patients with chronic constipation [83,[97][98][99][100]. ...
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Irritable bowel syndrome (IBS) is a common digestive disorder with a significant impact on both individuals and society in terms of quality of life and healthcare costs. A growing body of research has identified various communication pathways between the microbiota and the brain in relation to motility disorders, with the gut–brain axis being key to the pathogenesis of IBS. Multiple factors contribute to the pathogenetic pathways in IBS, including immune mechanisms, psychosocial factors, increased oxidative stress and pro-inflammatory cytokine release, as well as genetic and hormonal factors. Increased permeability of the normal intestinal barrier allows bacterial products to access the lamina propria, providing a mechanism for perpetuating chronic inflammation and characteristic symptoms. The microbiota influences inflammatory processes in IBS by altering the balance between pro-inflammatory factors and host defence. Probiotics modulate the pathophysiological mechanisms involved in IBS by influencing the composition of the microbiota and improving intestinal motility disorders, visceral hypersensitivity, immune function of the intestinal epithelium, metabolic processes in the intestinal lumen, dysfunction of the microbiota-GBA, and are recognised as effective and safe in IBS therapy. Our study aimed to provide a comprehensive overview of the relationship between the gut–brain axis, microbiota, and IBS, based on current information.
... Probiotics are live microorganisms that have a beneficial effect on humans when taken in appropriate amounts or as products containing such microorganisms. In Japan, probiotics are not covered by insurance for the treatment of chronic constipation, although many studies have reported that probiotics are effective against chronic constipation (68). However, the types of microorganisms used have varied among reports, so further evidence is required to establish their place as a standard treatment. ...
Article
Traditionally, the treatment of chronic constipation has focused on lifestyle modification, dietary guidance and therapy, and osmotic and stimulant laxatives. Recently, several drugs with new mechanisms of action have been introduced as treatments for chronic constipation. In Japan, polyethylene glycol and lactulose can now be administered under insurance coverage. The number of treatment options for constipation has increased dramatically. First, lifestyle modifications and dietary therapies must be implemented. If constipation does not improve sufficiently, specialized functional tests are performed to diagnose physiological subgroups. If functional tests are not available, patients are classified as having the "decreased frequency of defecation" type or the "difficult defecation" type based on the patient's symptoms, with treatment applied according to each type. Medical therapy includes osmotic laxatives, secretagogues, bile acid transporter inhibitors, probiotics, prokinetics, and Kampo medicines. The temporary use of stimulant laxatives, suppositories, enemas, and digital evacuation is also recommended. The usefulness of biofeedback is yet to be determined.
... After extensive clinical experience, several guidelines later advanced the idea of mixed constipation (MIX). The current treatment methods for FC include general treatments such as diet-ary modification [2]; discussions about exercise regulation as a potential contributing factor [3,4]; pharmacological treatments such as prokinetic drugs [5], bulking agents [6], stimulant laxatives [7] and microbial agents [8][9][10]; non-pharmacological therapies such as biofeedback therapy [11][12][13], sacral nerve stimulation [14] and surgery. ...
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Objective Functional constipation (FC) is a common intestinal disease worldwide. Despite the presence of criteria such as Roman IV, there is no standardized diagnosis and treatment algorithm in Hong Kong that combines both Western and Chinese medicine approaches. This study integrates current effective and safe diagnosis and treatment methods for FC and provides a clear and scientific pathway for clinical professionals and patients. Methods A systematic search of the PubMed, Cochrane Library, and China National Knowledge Infrastructure databases was performed from their inception to June 30th, 2022, collecting the current evidence about the efficacious integrative management for FC. We organized a meeting of professionals in fields relevant to treatment and management of FC to develop a consensus agreement on clinical pathway process. Results We developed a clinical pathway for the treatment of FC based on the most recent published guidelines and consultation with experts. This pathway includes a hierarchy of recommendations for every step of the clinical process, including clinical intake, diagnostic examination, recommended labs, diagnostic flowchart, and guidance for the selection of therapeutic drugs. Conclusion This pathway establishes clinical standards for the diagnosis and treatment of FC using Chinese medicine and Western medicine; it will help to provide high-quality medical services in Hong Kong for patients with FC.
... Data presented in this study provides an overview and useful information of some of these products, which may help consumers make rational choices in selecting suitable products. Nevertheless, there was some discrepancy in the result of probiotic effect on stool consistency between this work and another study [49]. The discrepancy is mainly because of the choice of applying the mean difference (MD) as the effect size indicator in this study, contrasting to standardized mean difference (SMD) previously used. ...
Article
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This study reviewed clinical evidence of probiotics-mediated effects on constipation. Four databases were used in the literature searches, namely Cochrane Library, Embase, Pubmed, and Web of Science. The last retrieval time was March 2021. Collected data were analyzed by Review Manager (version 5.3) and Stata (version 14). The primary search retrieved 8418 articles after removing duplicates. Eventually, 26 studies were included in the meta-analysis. Administration of probiotics significantly increased stool frequency (MD: 1.15 times/week; 95% CI: 0.59 to 1.70; P < 0.0001), improved bloating (MD: –0.48; 95% CI: –0.89 to –0.07; P = 0.02), reduced abdominal pain (MD: –0.71; 95% CI: –1.25 to –0.16; P = 0.01), and improved quality of life (MD: –0.73; 95% CI: –1.37 to –0.10; P = 0.02). However, the clinical effect of intake of probiotics on stool consistency was non-significant (MD: 0.07; 95% CI: –0.34 to 0.48; P = 0.73). Based on our analysis, probiotic supplements were effective in relieving constipation through symptom improvement. The effectiveness of dosage forms of intervention ranked: capsules > others (tablets, powder) > fermented milk.
... This has led to the use of probiotics 4,5 and numerous trials have been conducted in both animals and humans to evaluate the effectiveness of probiotics in managing constipation. [6][7][8] In recent times, attention has been focused on enhancing the benefits of probiotics by combining them with prebiotics. Prebiotics as an additive, have several advantages such as being more resistant to digestive enzymes, being more costeffective, carrying fewer risks, and being easier to include in the diet. ...
... With respect to the constipation profile of the subjects, the frequency of stools was considerably enhanced by GOS consumption as compared to the placebo-fed group. In a large number of patients with functional constipation, a rise of 1.01 bowel movements per week by prebiotic ingestion normalized stool frequency [26]. Prebiotics such as GOS are dietary components that have the ability to alter the intestinal microbiota of the host without causing any adverse effects such as abdominal discomfort, flatulence or the development of pathogenic intestinal microbiota. ...
Article
Functional constipation affects approximately 10% of the Indian population and may reduce the quality of life (QOL) and increase gut dysbiosis. The study aimed at assessing the impact of galactooligosaccharide (GOS) gummy supplementation on gut health, depression status and QOL of constipated subjects. A double-blind placebo control clinical trial (CTRI/2021/10/037474) was conducted on sedentary constipated adults (n = 35), who were split into an experimental group (n = 17) and a control group (n = 18), supplemented with 10 g GOS and sugar gummies, respectively, for 30 days. Relative abundance of fecal gut microbes, including Bifidobacterium, Lactobacillus, Clostridium and Bacteroides and phyla Bacteroidetes and Firmicutes using real-time polymerase chain reaction and short-chain fatty acids, was analyzed pre and post supplementation. Constipation profile was studied using Rome IV criteria and the Bristol stool chart. Depression status was studied using the Becks Depression Inventory. The QOL was assessed using patient assessment of constipation. GOS gummy supplementation increased Bifidobacterium and Lactobacillus by 1230% and 322%, respectively, (p < 0.001; p < 0.01) with reduced Clostridium by 63%, phylum Firmicutes by 73% and Bacteroidetes by 85% (p < 0.01). The GOS-supplemented group demonstrated a higher F/B ratio (4.2) indicating improved gut health (p < 0.01) with reduced gut dysbiosis and constipation severity. GOS gummies enhanced acetic acid and butyric acid levels compared to the control group (p < 0.01; p < 0.001). Post supplementation, there was 40% reduction in depression (p < 0.01) and 22% improvement in QOL (p < 0.05). This research validates the predicted beneficial benefits of short-term GOS consumption on constipation profile, gut microflora, depression status and quality of life of constipated subjects.
... Another meta-analysis found that multi-strain probiotics effectively improved stool frequency and consistency (16). ...
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Background Parkinson’s disease (PD) is one of the common neurodegenerative diseases, and there has been an increasing interest in the potential role of intestinal dysbiosis in its pathogenesis and related gastrointestinal complications such as constipation. Objectives This study aims to evaluate the effects of multi-strain probiotics on constipation and motor function in PD patients. Methods This study was a blinded, randomized controlled trial (RCT) that involved 27 PD patients who were diagnosed with constipation according to the ROME IV criteria for functional constipation. The primary outcome measured before and after the intervention in both the placebo and probiotic groups was the frequency of defecation. Secondary outcomes evaluated were laxative use, sense of complete evacuation, Bristol Stool Scale for consistency, and Unified Parkinson’s Disease Rating Scale (UPDRS) scale. The study lasted for eight weeks. Both groups also were educated about lifestyle modification. Results Of 30 included patients (15 in each group), 13 were women, and 17 were men. Three patients dropped out of the study. Between-group analysis showed that the frequency of bowel movements significantly increased in the probiotic group 4 [3 - 5] in comparison with 2 [2 - 3] in placebo (P = 0.02). Stool consistency also improved in the probiotic group (P = 0.04). However, there were no significant differences in other outcomes. The within-group analysis showed improvement in stool consistency in both probiotics and placebo groups (P = 0.01 and P = 0.007, respectively), while stool frequency and sense of complete evacuation significantly improved only in the probiotic group (P < 0.05). Conclusions This study demonstrated that multi-strain probiotics could improve frequency, consistency, and sense of complete evacuation in PD patients, while there was no significant effect on motor functions in 8 weeks. It is suggested that additional studies be conducted on longer-term effects.
... A meta-analysis analyzing the effect of probiotics on functional constipation in adults showed that probiotics reduced whole gut transit time significantly and improved incomplete evacuation. 209 Summary of findings is presented in Supplementary Figure 10. Considering the above results, probiotics seem to increase the frequency of bowel movements and alleviate symptoms of functional constipation. ...
Article
Chronic constipation is one of the most common digestive diseases encountered in clinical practice. Constipation manifests as a variety of symptoms, such as infrequent bowel movements, hard stools, feeling of incomplete evacuation, straining at defecation, a sense of anorectal blockage during defecation, and use of digital maneuvers to assist defecation. During the diagnosis of chronic constipation, the Bristol Stool Form Scale, colonoscopy, and a digital rectal examination are useful for objective symptom evaluation and differential diagnosis of secondary constipation. Physiological tests for functional constipation have complementary roles and are recommended for patients who have failed to respond to treatment with available laxatives and those who are strongly suspected of having a defecatory disorder. As new evidence on the diagnosis and management of functional constipation emerged, the need to revise the previous guideline was suggested. Therefore, these evidence-based guidelines have proposed recommendations developed using a systematic review and meta-analysis of the treatment options available for functional constipation. The benefits and cautions of new pharmacological agents (such as lubiprostone and linaclotide) and conventional laxatives have been described through a meta-analysis. The guidelines consist of 34 recommendations, including 3 concerning the definition and epidemiology of functional constipation, 9 regarding diagnoses, and 22 regarding managements. Clinicians (including primary physicians, general health professionals, medical students, residents, and other healthcare professionals) and patients can refer to these guidelines to make informed decisions regarding the management of functional constipation.
... Conventionally, probiotics are used for intestinal regulation by replacing the toxic intestinal flora responsible for diseases, such as bacterial enteritis [6]. However, considering that constipation could be caused by a disturbance of intestinal bacteria, it has recently gained attention as an important disease that requires treatment [7]. Moreover, it improves intestinal flora and can be used as a remedy for elderly patients with an increasing number of harmful intestinal bacteria that are assumed to cause constipation. ...
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Background Chronic constipation is a prevalent, burdensome gastrointestinal disorder whose etiology and pathophysiology remain poorly understood. Differences in the composition of the intestinal microbiota have been shown between constipated patients and healthy people. Data indicate that these microbial differences contribute to the disorder. Methods Preclinical studies in mice examined the effects of Lactobacillus gasseri on intestinal motility ex vivo, the reversal of motility inhibition by μ‐opioid receptor agonists ex vivo and in vivo in mice, and the effects on capsaicin‐stimulated transient receptor potential vanilloid 1 (TRPV1) in Jurkat cells. Thereafter, a clinical study of 40 women with functional constipation was conducted to investigate the effects of Lactobacillus gasseri with a randomized parallel design. After 14 days of baseline recording, treatment with Lactobacillus gasseri or placebo was given over 28 days, with 14 days of follow‐up. Outcomes with complete spontaneous bowel movements (CSBM), spontaneous bowel movements, emptying frequency, abdominal pain, time spent for defecation, Bristol stool form scale, use of rescue laxatives, and impact on sex life were investigated. Key Results In preclinical studies, Lactobacillus gasseri increased intestinal motility in an ex vivo model, reversed the motility inhibition caused by μ‐opioid receptor agonist ex vivo and in vivo in mice, and counteracted capsaicin‐stimulated activity of TRPV1 in Jurkat cells. In the clinical trial, Lactobacillus gasseri showed a significant reduction in abdominal pain, along with a correlation and tendency for an increased number of CSBM. Few adverse events were encountered. Conclusions and Inferences Treatment with Lactobacillus gasseri can alleviate pain sensations in functional constipation, possibly with an improved bowel‐emptying function.
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Microorganisms have long been used to produce primary and secondary metabolites essential for human health and environmental sustainability. Due to their rapid growth and reproduction rates, as well as their ability to undergo genetic modifications, microorganisms play a critical role in the manufacturing industry. Probiotics, which are non-pathogenic microorganisms, have gained significant interest due to their various health benefits, including treating vitamin deficiencies, alleviating digestive disorders, enhancing immunity, and detoxifying harmful substances. Probiotics are commonly used to address gastrointestinal issues such as inflammatory bowel disease, as well as conditions like obesity, diabetes, constipation, and colon cancer. Despite these applications, recent advancements in understanding the role of probiotics in managing these diseases have been limited. This review presents the latest insights into probiotics' role in health management. With the growing global population, researchers are focusing on strategies to meet the increasing demand for probiotics. Using advanced techniques, scientists are exploring probiotic strains that can be produced industrially and utilized to treat various medical conditions. This review compiles essential information for probiotic researchers, covering strain selection, production, and applications.
Article
Background: Probiotic administration may decrease the incidence of necrotizing enterocolitis (NEC) through mechanisms that are largely unknown. We investigated the effects of probiotics on intestinal epigenetics and assessed their effects on intestinal inflammation and motility using both ileum-predominant and combined ileo-colitis mouse NEC models. Methods: C57BL/6 J mice were gavage-fed a multi-strain probiotic from postnatal days 3-11, consisting of B. infantis, B. lactis, and S. thermophilus. From p8, mice were exposed to ileo-colitis NEC involving formula containing NEC bacteria and 0.5% DSS. DNA methylation was measured using the Infinium Methylation Assay. Gastrointestinal motility was assessed by 70 Kd FITC-dextran transit time. Probiotic colonization was measured in probiotic-fed mice by qPCR. Results: Probiotic administration caused significant changes in the small intestine's epigenetic signature, a reduction in NEC severity, and improved intestinal motility. The effects of probiotics were more pronounced in the ileo-colitis NEC model. Conclusions: These findings shed light on the role of probiotics in two clinically relevant models of NEC, add additional insights into their underlying mechanism of action, and reveal unanticipated epigenetic modifications to the intestinal mucosa after their use. Impact: These findings shed light on the role of multi-strain probiotics in two clinically relevant animal models of NEC, and add additional insights into their underlying mechanism of action This study provides a new, clinically relevant model for the study of NEC including administration of 0.5% DSS, to include ileal dominant and ileo-colonic dominant phenotypes of the disease. These results reveal that clinically relevant strains of probiotic bacteria can exert epigenetic effects on the small intestine in mice, and can attenuate the epigenetic changes induced by NEC.
Article
In July 2023 the Japan Gastroenterological Association published the first version of its clinical guidelines for chronic constipation 2023. Based on the latest evidence, these guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic constipation. They include flowcharts for both diagnosis and treatment of chronic constipation. In the treatment of chronic constipation, the first step involves differentiating between secondary forms, such as organic disease-associated constipation, systemic disease-associated constipation, and drug-induced constipation. The next step is to determine whether the chronic constipation stems from a motility disorder, a form of primary chronic constipation. For functional constipation and constipation-predominant irritable bowel syndrome, treatment should be initiated after evaluating symptoms like reduced frequency of bowel movement frequency type or defecation difficulty type. The first line of treatment includes improvement of lifestyle habits and diet therapy. The first drugs to consider for oral treatment are osmotic laxatives. If these are ineffective, secretagogues and ileal bile acid transporter inhibitors are candidates. However, stimulant laxatives are exclusively designated for as-needed use. Probiotics, bulk-forming laxatives, prokinetics, and Kampo medicine, for which there is insufficient evidence, are considered alternative or complementary therapy. Providing the best clinical strategies for chronic constipation therapy in Japan, these clinical guidelines for chronic constipation 2023 should prove useful for its treatment worldwide.
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This book is a detailed, evidence-based reference on the field of integrative geriatric medicine. It is intended for all healthcare providers and advocates who work with the geriatric population—in outpatient settings and nursing homes, assisted and independent living facilities, and senior community centers. In addition, it will provide valuable information for leaders and politicians who are involved with implementing policies and procedures for the care of elderly patients and who are looking for safer, less costly, and more patient-centered approaches. Integrative geriatrics is a new field of medicine that advocates for a whole-person, patient-centered, primarily non-pharmacological approach to medical care of the elderly. Most current geriatric practices overprescribe medications and procedures and underutilize non-pharmacological, low-cost, high-touch methods. Patients, however, often show reluctance toward these standard practices because they often involve invasive interventions. The practice of integrative geriatrics is rooted in lifestyle interventions, such as nutrition, movement therapies, and mind-body and spirituality approaches, that allow patients to take a different path to their health, one that utilizes pharmaceuticals and invasive procedures only when safer integrative approaches are not available or not effective.
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Over 90% of patients with systemic sclerosis develop gastrointestinal disease. Involvement of the lower gastrointestinal tract, including the small intestine, colon, and anorectum is common and may be associated with significant morbidity and mortality. This chapter will focus on providing a comprehensive review of the pathophysiology, clinical presentation, approach to diagnosis, as well as the management of systemic sclerosis-related manifestations of the lower gastrointestinal tract.
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Constipation is a prevalent clinical ailment of the gastrointestinal system, yet its pathogenesis remains ambiguous. Despite the availability of numerous treatment modalities, they are insufficient in resolving the issue for patients. This work conducted a comprehensive review of the existing literature pertaining to the utilization of natural products for the treatment of constipation, with a focus on the efficacy of natural products in treating constipation, and to provide a comprehensive summary of their underlying mechanisms of action. Upon conducting a thorough review of the extant literature, we found that natural products can effectively treat constipation as modern synthetic drugs and compounded drugs with acetylcholinesterase (AChE) effects, rich in fiber and mucus, and the effects of increasing the tension of the ileum and gastrointestinal tract muscle, mediating signaling pathways, cytokine, excitability of the smooth muscle of the gastrointestinal tract, and regulating the homeostasis of intestinal flora. However, there is a wide variety of natural products, and there are still relatively few studies; the composition of natural products is complex, and the mechanism of action of natural products cannot be clarified. In the future, we need to further improve the detailed mechanism of natural products for the treatment of constipation.
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Enzymes, which are protein molecules acting as catalysts in biological reactions, find diverse applications in various industries, including the production of halal products. Ensuring the halal status of enzymes necessitates considering their source and production methods. In meat processing, enzymes are utilized to tenderize meat, improve texture, and enhance flavor. Enzymes serve as crucial tools in the production of halal products, contributing to their quality, texture, flavor, and shelf life. To maintain the halal status of the final products, it is imperative to select enzymes derived from halal sources and produced in accordance with halal guidelines. The objective of this book chapter is to emphasize the origin of enzymes and their applications in producing specific halal products, thereby highlighting their significance in the industry.
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Humans serve as hosts for various species of microorganisms that contribute to the maintenance of human health. The beneficial bacteria residing in our bodies are referred to as probiotics. Besides improving the immune system, probiotics are also capable of warding off various diseases. In recent decades, probiotic microorganisms have emerged as a significant factor in human well-being. Popularly referred to as "health-friendly microorganisms," they influence health in myriad ways by boosting the immune system, combating intestinal irritation, improving the balance of the gut microbiome, lowering blood pressure, relieving postmenopausal symptoms, and reducing traveler’s diarrhea. The ability of probiotics to compete for the adhesion sites of pathogenic microbes makes them an effective treatment against various intestinal pathogens. Recent studies also advocate their use in the treatment of skin and oral diseases. In addition, the modulation of gut flora by probiotics is being discussed as a possible new solution for treating tension and depression. Ultimately, a cost-effective approach is imperative to improve and maintain fitness in the present competitive environment. This review aims to evaluate the potential benefits of probiotic microorganisms in various disorders, such as gastrointestinal disorders, UTIs, acne, anticancer properties, gut-brain connections, and their possible mode of action.
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Context Constipation is a very common symptom in the general population. One way of non-pharmacological treatment of constipation is through the addition of probiotics to food. Obectives The aim of this study was to evaluate de effect of the consumption of a fresh cheese, enriched with Bifidobacterium lactis Bi-07 on the symptoms of constipated women. Methods A randomized controlled trial, carried out in the Basic Health Units of Guaporé's City – RS/Brazil, between january and may 2012, with 30 constipated women. The patients were randomized into two groups whom received, for 30 days, 30 g of fresh cheese enriched with Bifidobacterium lactis Bi-07 (n = 15) or regular fresh cheese (n = 15). Constipation symptoms were evaluated according to ROMA III Consensus, before and after the nutritional intervention. Also, data of clinical and anthropometric characteristics of the individuals were collected. Accepted level of significance 5% (P≤0,05). Results The medium age of the studied population was 37,5±14,4 years in the intervention group and 40,8±12,8 years in the control group. After 30 days we observed that the ingestion of fresh cheese enriched with Bifidobacterium lactis Bi-07 promoted benefic effects on the symptoms of strength to evacuate. Conclusion The consumption of 30g/day of a fresh cheese enriched with Bifidobacterium lactis Bi-07 has beneficial effects on constipation symptoms.
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Background: Data on factors affecting treatment satisfaction in European women with chronic constipation are limited. Objective: To assess factors associated with treatment satisfaction among European women with chronic constipation. Methods: A 2011-2012 internet survey was conducted in men and women from 12 European countries. Respondents analysed were female with self-reported chronic constipation (≥1 symptoms for ≥6 months of lumpy/hard stools, feeling of incomplete evacuation, and pain during defecation, as well as <3 bowel movements/week). For laxative users, satisfaction with treatment, factors affecting satisfaction, and interactions with healthcare professionals were collected. Results and conclusions: In total, 4805/50,319 participants fulfilled the inclusion criteria (female with chronic constipation). Of the laxative users (1575/4805), 57% (n = 896) were satisfied with their treatment, while 26% were neutral, and 17% dissatisfied. Dissatisfied respondents visited their GP less frequently in the past 12 months, were more likely to obtain over-the-counter laxatives, and took a dose higher than recommended more frequently than those satisfied. Respondents were most satisfied with ease of use of treatment and least satisfied with relief from bloating. Newer treatments aimed at alleviating symptoms, particularly bloating, are required for respondents neutral or dissatisfied with their current treatment.
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Irritable bowel syndrome (IBS) and chronic constipation (CC) are common functional gastrointestinal disorders affecting 14% and 20% of the U.S. population, respectively. Reviews of the evidence on the burden of illness associated with IBS and CC have not been comprehensive in scope and have not provided an assessment of the distribution of health care costs across categories of resource use. To (a) identify studies from any geographic region or country perspective that measure the economic burden of the disease; (b) analyze the direct (medical, drug, and other components) and indirect costs of illness; and (c) assess published evidence of the humanistic burden as measured by quality of life (QOL). An electronic literature search was conducted using journal databases, including MEDLINE, The Cochrane Library, EconLit, CINAHL, and Digestive Disease Week meeting abstracts. Specific search terms used were "irritable bowel syndrome" and "chronic constipation." In databases that accommodated Boolean searches, terms related to economic and quality of life outcomes were incorporated. Studies were included if they evaluated patients with an IBS or CC diagnosis and quantitatively measured the economic or humanistic burden of disease. Results were descriptively analyzed. The search identified a total of 882 unique publications. Thirty-five articles and abstracts met the inclusion criteria. Studies included 1,706 IBS-C, 2,264 IBS-D, 2,892 IBS-A, 15,830 IBS unclassified, and 1,278 CC patients. Nineteen of 35 studies assessed cost-of-illness endpoints, and from the U.S. perspective, the direct cost per-patient for IBS ranged from 1,562to1,562 to 7,547 per year, while direct costs of CC ranged from 1,912to1,912 to 7,522 per year. From the U.S. perspective, the indirect costs of IBS ranged from 791to791 to 7,737 per year, and no study assessed the indirect costs of CC. For IBS, data on the distribution of costs attributable to categories of resource use varied widely, particularly outpatient costs (12.7% to greater than 50% of total costs), inpatient costs (6.2% to 40.8%), and pharmacy or drug costs (5.9% to 46.6%). Comparable data on CC were not identified. Nineteen studies of IBS patients measured the humanistic burden of disease; 14 studies utilized SF-36; and within-study domain scores were significantly lower in IBS patients compared with non-IBS controls. Only 1 study of CC patients reported humanistic burden of disease. The studies identified in the systematic review varied in the method used to identify patients with IBS and CC. Results were not typically reported by IBS subtype. We observed a large variation in attributable direct and indirect costs and drivers of these costs. Future research should refine burden of illness estimates to subtypes so that estimates associated with IBS-C and CC are differentiated.
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To determine the efficacy of probiotic supplementation on intestinal transit time (ITT) and to identify factors that influence these outcomes. A systematic review of randomized controlled trials (RCTs) of probiotic supplementation that measured ITT in adults was conducted by searching MEDLINE and EMBASE using relevant key word combinations. Main search limits included RCTs of probiotic supplementation in healthy or constipated adults that measured ITT. Study quality was assessed using the Jadad scale. A random effects meta-analysis was performed with standardized mean difference (SMD) of ITT between probiotic and control groups as the primary outcome. Meta-regression and subgroup analyses were conducted to examine the impact of moderator variables on ITT SMD. A total of 11 clinical trials with 13 treatment effects representing 464 subjects were included in this analysis. Probiotic supplementation was associated with decreased ITT in relation to controls, with an SMD of 0.40 (95%CI: 0.20-0.59, P < 0.001). Constipation (r (2) = 39%, P = 0.01), higher mean age (r (2) = 27%, P = 0.03), and higher percentage of female subjects (r (2) = 23%, P < 0.05) were predictive of decreased ITT with probiotics in meta-regression. Subgroup analyses demonstrated statistically greater reductions in ITT with probiotics in subjects with vs without constipation and in older vs younger subjects [both SMD: 0.59 (95%CI: 0.39-0.79) vs 0.17 (95%CI: -0.08-0.42), P = 0.01]. Medium to large treatment effects were identified with Bifidobacterium Lactis (B. lactis) HN019 (SMD: 0.72, 95%CI: 0.27-1.18, P < 0.01) and B. lactis DN-173 010 (SMD: 0.54, 95%CI: 0.15-0.94, P < 0.01) while other single strains and combination products yielded small treatment effects. Overall, short-term probiotic supplementation decreases ITT with consistently greater treatment effects identified in constipated or older adults and with certain probiotic strains.
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Chronic constipation is a very common symptom that is rarely associated with life-threatening diseases, but has a substantial impact on patient quality of life and consumption of healthcare resources. Despite the large number of affected patients and the social relevance of the condition, no cost-effectiveness analysis has been made of any diagnostic or therapeutic algorithm, and there are few data comparing different diagnostic and therapeutic approaches in the long term. In this scenario, increasing emphasis has been placed on demonstrating that a number of older and new therapeutic options are effective in treating chronic constipation in well-performed randomised controlled trials, but there is still debate as to when these therapeutic options should be included in diagnostic and therapeutic algorithms. The aim of this review is to perform a critical evaluation of the current diagnostic and therapeutic options available for adult patients with chronic constipation in order to identify a rational patient approach; furthermore we attempt to clarify some of the more controversial points to aid clinicians in managing this symptom in a more efficacious and cost-effective manner.
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Measurement of colon transit time is the most basic and primary tool in evaluating disorders of colonic motility. In particular, it is helpful in pathologic diagnosis and for planning management in patients with constipation. Several techniques for measuring colon transit time currently exist. The standard measurement of colon transit time has been performed using radioopaque marker test. The radioopaque marker test is the most widely used method; it is simple to perform as well as being cost effective. But, this technique produces radiation exposure. Radionuclide scintigraphy and wireless motility capsules are other techniques used to measure colon transit time. In radionuclide scintigraphy, the transit of radioisotope is viewed by gamma camera; this approach has an advantage in that it uses minimal radiation and it allows a physiological assessment of gastrointestinal transit. Wireless motility capsules have been validated most recently, but this technique is not useful in Korea. This review presents the techniques used to measure colon transit time and the interpretations provided in different colon transit studies.
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Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30
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To assess the impact of Bifidobacterium lactis HN019 supplementation on whole gut transit time (WGTT) and frequency of functional gastrointestinal (GI) symptoms in adults. We randomized 100 subjects (mean age: 44 years; 64% female) with functional GI symptoms to consume a proprietary probiotic strain, B. lactis HN019 (Fonterra Research Centre, Palmerston North, New Zealand), at daily doses of 17.2 billion colony forming units (CFU) (high dose; n = 33), 1.8 billion CFU (low dose; n = 33), or placebo (n = 34) for 14 days. The primary endpoint of WGTT was assessed by X-ray on days 0 and 14 and was preceded by consumption of radiopaque markers once a day for 6 days. The secondary endpoint of functional GI symptom frequency was recorded with a subject-reported numeric (1-100) scale before and after supplementation. Decreases in mean WGTT over the 14-day study period were statistically significant in the high dose group (49 ± 30 to 21 ± 32 h, p < 0.001) and the low dose group (60 ± 33 to 41 ± 39 h, p = 0.01), but not in the placebo group (43 ± 31 to 44 ± 33 h). Time to excretion of all ingested markers was significantly shorter in the treatment groups versus placebo. Of the nine functional GI symptoms investigated, eight significantly decreased in frequency in the high dose group and seven decreased with low dose, while two decreased in the placebo group. No adverse events were reported in any group. Daily B. lactis HN019 supplementation is well tolerated, decreases WGTT in a dose-dependent manner, and reduces the frequency of functional GI symptoms in adults.
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Chronic idiopathic constipation (CIC) is a common functional gastrointestinal disorder in the community, yet no previous systematic review and meta-analysis has estimated the global prevalence, or potential risk factors for the condition. MEDLINE, EMBASE, and EMBASE Classic were searched (up to December 2010) to identify population-based studies reporting the prevalence of CIC in adults (≥15 years), according to self-report, questionnaire, or specific symptom-based criteria. The prevalence of CIC was extracted for all studies, and according to country, age, gender, socioeconomic status, and presence or absence of irritable bowel syndrome (IBS) where reported. Pooled prevalence overall, and according to study location and certain other characteristics, as well as odds ratios (ORs), with 95% confidence intervals (CIs) were calculated. Of the 100 papers evaluated, 45 reported the prevalence of CIC in 41 separate study populations, containing 261,040 subjects. Pooled prevalence of CIC in all studies was 14% (95% CI: 12-17%). The prevalence of CIC was lower in South East Asian studies, and in studies using the Rome II or III criteria. The prevalence of CIC was higher in women (OR: 2.22; 95% CI: 1.87-2.62), and increased with age and lower socioeconomic status. The prevalence was markedly higher in subjects who also reported IBS (OR: 7.98; 95% CI: 4.58-13.92), suggesting common pathogenic mechanisms. Pooled prevalence of CIC in the community was 14%, and of similar magnitude in most geographical regions. Rates were higher in women, older individuals, and those of lower socioeconomic status. Presence of IBS was strongly associated with CIC.
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Clinical researchers have often preferred to use a fixed effects model for the primary interpretation of a meta-analysis. Heterogeneity is usually assessed via the well known Q and I2 statistics, along with the random effects estimate they imply. In recent years, alternative methods for quantifying heterogeneity have been proposed, that are based on a 'generalised' Q statistic. We review 18 IPD meta-analyses of RCTs into treatments for cancer, in order to quantify the amount of heterogeneity present and also to discuss practical methods for explaining heterogeneity. Differing results were obtained when the standard Q and I2 statistics were used to test for the presence of heterogeneity. The two meta-analyses with the largest amount of heterogeneity were investigated further, and on inspection the straightforward application of a random effects model was not deemed appropriate. Compared to the standard Q statistic, the generalised Q statistic provided a more accurate platform for estimating the amount of heterogeneity in the 18 meta-analyses. Explaining heterogeneity via the pre-specification of trial subgroups, graphical diagnostic tools and sensitivity analyses produced a more desirable outcome than an automatic application of the random effects model. Generalised Q statistic methods for quantifying and adjusting for heterogeneity should be incorporated as standard into statistical software. Software is provided to help achieve this aim.
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There has been no definitive systematic review and meta-analysis to date examining the effect of laxatives and pharmacological therapies in chronic idiopathic constipation (CIC). To assess efficacy of these therapies systematically in CIC. Systematic review and meta-analysis of randomised controlled trials (RCTs). MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (up to September 2010). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Placebo-controlled trials of laxatives or pharmacological therapies in adult CIC patients were eligible. Minimum duration of therapy was 1 week. Trials had to report either a dichotomous assessment of overall response to therapy at last point of follow-up in the trial, or mean number of stools per week during therapy. Symptom data were pooled using a random effects model. Effect of laxatives or pharmacological therapies compared to placebo was reported as RR of failure to respond to therapy, or a weighted mean difference (WMD) in mean number of stools per week, with 95% CIs. Twenty-one eligible RCTs were identified. Laxatives (seven RCTs, 1411 patients, RR=0.52; 95% CI 0.46 to 0.60), prucalopride (seven trials, 2639 patients, RR=0.82; 95% CI 0.76 to 0.88), lubiprostone (three RCTs, 610 patients, RR=0.67; 95% CI 0.56 to 0.80), and linaclotide (three trials, 1582 patients, RR=0.84; 95% CI 0.80 to 0.87) were all superior to placebo in terms of a reduction in risk of failure with therapy. Treatment effect remained similar when only RCTs at low risk of bias were included in the analysis. Diarrhoea was significantly more common with all therapies. Only two RCTs were conducted in primary care, and total adverse events data for laxatives and linaclotide were sparse. Laxatives, prucalopride, lubiprostone and linaclotide are all more effective than placebo for the treatment of CIC.
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Comparison of quality of life (QoL) across disease areas requires the use of appropriate tools. Although many studies have investigated QoL in constipation, most used disease-specific tools that are inappropriate for cross-comparisons. To identify studies of QoL in constipation and to compare these results with other chronic conditions. A comprehensive literature search identified studies in constipation that used a generic QoL tool. Results were statistically pooled where possible and compared with published results using the same tools in other chronic conditions. A total of 13 qualifying studies were identified, 10 in adults and three in children. Results from eight studies using the SF-36/12 tools were pooled; the remaining five were narratively reported. Mental and physical components of QoL scores were consistently impaired in both adult and child populations, with the greatest impact being seen in secondary care studies. Mental health effects predominated over physical domains. The magnitude of impact was comparable with that seen in patients with allergies, musculoskeletal conditions and inflammatory bowel disease. The impact of constipation on QoL is significant and comparable with other common chronic conditions. Improving management may prove to be an effective way of improving QoL for a substantial number of patients.
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Despite a lack of supportive data, stool form and stool frequency are often used as clinical surrogates for gut transit in constipated patients. The aim of this study was to assess the correlation between stool characteristics (form and frequency) and gut transit in constipated and healthy adults. A post hoc analysis was performed on 110 subjects (46 chronic constipation) from nine US sites recording stool form (Bristol Stool Scale) and frequency during simultaneous assessment of whole-gut and colonic transit by wireless motility capsule (WMC) and radio-opaque marker (ROM) tests. Stool form and frequency were correlated with transit times using Spearman's rank correlation. Accuracy of stool form in predicting delayed transit was assessed by receiver operating characteristic analysis. In the constipated adults (42 females, 4 males), moderate correlations were found between stool form and whole-gut transit measured by WMC (r=-0.61, P<0.0001) or ROM (-0.45, P=0.0016), as well as colonic transit measured by WMC (-0.62, P<0.0001). A Bristol stool form value <3 predicted delayed whole-gut transit with a sensitivity of 85% and specificity of 82% and delayed colonic transit with a sensitivity of 82% and specificity of 83%. No correlation between stool form and measured transit was found in healthy adults, regardless of gender. No correlation was found between stool frequency and measured transit in constipated or healthy adults. The correlation between stool frequency and measured transit remained poor in constipated adults with <3 bowel movements per week. Stool form predicts delayed vs. normal transit in adults. However, only a moderate correlation exists between stool form and measured whole-gut or colonic transit time in constipated adults. In contrast, stool frequency is a poor surrogate for transit, even in those with reduced stool frequency.
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Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement—a reporting guideline published in 1999—there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (http://www.prisma-statement.org/) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
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The sitz or plastic marker study for colonic transit has been around for many years. It is applicable where an X-ray machine exists, is widely used and is accepted as the gold standard for diagnosing constipation. Recently, radiopharmaceutical methods have been developed. The theme of this review is their possible roles in the assessment of paediatric bowel motility disorders in patients presenting to paediatric surgeons. This review presents data on total and segmental transit in normal adults and children and comparing the two techniques in adults. Reliability and reproducibility are presented. Normative data for colonic transit in adults and children are discussed and parameters for assessing abnormal transit are reviewed. Normal colonic transit takes 20-56 h. Plastic marker studies are more readily accessible, but the assessment may be misleading with current methods. Plastic markers show faster transit than scintigraphy. It is difficult to compare the two techniques because methods of reporting are different. Using scintigraphy, repeatability is good. Separation of normal from slow transit in the ascending colon is apparent at 24 and 48 h, but the determination of transit through the distal colon/rectum in adults may require studies of more than 7 days. In conclusion, plastic marker studies and scintigraphy show similar transit rates in young adults and children. However, scintigraphy has advantages of allowing transit through the stomach and small intestine to be measured and has proved useful in the diagnostic workup of children with intractable constipation.
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Systematic reviews (SRs) are an increasingly popular evidence-based tool and are often used to answer complex research questions across many different research domains. Early SR methodology was advanced by social scientists, and the term meta-analysis was coined by a social scientist who also conducted research in psychology. SRs have recently become popular in healthcare and are likely to be beneficial in any field. The aim of this report is to highlight issues in SR conduct with a focus on the field of nutrition and to make recommendations on improving SR conduct in this area. Development of the research question is probably the most important step in conducting an SR. The 4 main components of an answerable question are 1) the patient, population, or problem; 2) the intervention, independent variable, or exposure; 3) the comparators; and 4) the dependent variables or outcomes of interest. The question will be used to determine the optimal methods for conducting the SR. SRs often include study designs beyond randomized trials and do not always include a meta-analysis of the results. Other topics explored include understanding and interpreting discordant reviews and the importance of reporting tools [eg, QUality Of Reporting Of Meta-analyses (QUOROM Statement) or CONsolidated Standards Of Reporting of Trials (CONSORT Statement)]. Recommendations are then provided, such as developing a capacity-building program, searching the primary literature for research gaps, and extending reporting tools such as the QUOROM Statement to the field of nutrition.
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Because the range of bowel habits and stool types in the community is unknown we questioned 838 men and 1059 women, comprising 72.2% of a random stratified sample of the East Bristol population. Most of them kept records of three consecutive defecations, including stool form on a validated six point scale ranging from hard, round lumps to mushy. Questionnaire responses agreed moderately well with recorded data. Although the most common bowel habit was once daily this was a minority practice in both sexes; a regular 24 hour cycle was apparent in only 40% of men and 33% of women. Another 7% of men and 4% of women seemed to have a regular twice or thrice daily bowel habit. Thus most people had irregular bowels. A third of women defecated less often than daily and 1% once a week or less. Stools at the constipated end of the scale were passed more often by women than men. In women of child bearing age bowel habit and the spectrum of stool types were shifted towards constipation and irregularity compared with older women and three cases of severe slow transit constipation were discovered in young women. Otherwise age had little effect on bowel habit or stool type. Normal stool types, defined as those least likely to evoke symptoms, accounted for only 56% of all stools in women and 61% in men. Most defecations occurred in the early morning and earlier in men than in women. We conclude that conventionally normal bowel function is enjoyed by less than half the population and that, in this aspect of human physiology, younger women are especially disadvantaged.
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Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews. Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision. In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias. A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution.
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During the fermentation of lactulose, short-chain fatty acids are formed with consequent lowering of the colon pH and modification of the microflora. Lactulose promotes the growth of lactic acid bacteria and bifidobacteria and, more specifically, Lactobacillus acidophilus in the colon. Lactulose and lactulose-containing products fermented with lactic acid bacteria lower colonic pH balancing intestinal microecology and normalizing intestinal transit. In animal studies, lactulose promotes a mainly Grampositive faecal microflora, but large doses of lactulose may be associated with transient diarrhoea. Our studies indicate that lactulose with lactic acid bacteria effectively relieves constipation in human volunteers. Lactulose with lactic acid bacteria in a fermented diary product can balance and prevent radiotherapy-associated diarrhoea and intestinal side effects. Normalizing the intestinal flora and stabilizing mucosal integrity with lactulose has beneficial effects in intestinal disorders. Lactulose and lactic acid bacteria offer a promising ingredient combination for future functional and special dietary foods in treating intestinal disturbances.
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Background: The consequence of constipation should not be ignored, however, the relationship between probiotic yogurt and constipation has not been directly investigated. Aims: To investigate the effect of probiotic yogurt containing Bifidobacterium animalis strain DN-173 010 on symptoms of constipation. Methods: A total of 159 adults with constipation were randomly allocated to consume either 100 g of a probiotic yogurt containing DN-173 010 (test group) or 100 g of an acidified milk (control group) for 2 weeks. Stool frequency, defecation status, stool consistency and food intake at baseline and during test period were recorded. Results: Following consuming probiotic yogurt containing DN-173 010, the stool frequency and score of defecation status and stool consistency improved significantly as compared with the baseline values (P<0.01). Compared with control group, stool frequency increased significantly after 1 and 2 weeks of yogurt consumption, and the score of defecation status and stool consistency decreased significantly (P=0.000). No significant difference was found in food intake during test period between the two groups. Conclusions: Consumption of probiotic yogurt containing Bifidobacterium animalis strain DN-173 010 has a beneficial effect on constipation symptoms in adults with constipation.
Article
The aim of this study was to investigate the effect of a fermented milk drink containing Lactobacillus casei Shirota (LcS) on the bowel habit (with emphasis on stool consistency) of subjects suffering from hard stools. Secondly, it was tested whether the probiotic strain (LcS), was able to survive throughout the gastrointestinal tract. A double-blind, placebo-controlled, randomized study was carried out over an eight-week period in subjects with symptoms of constipation (n=120). To all subjects, 65 ml/day of a probiotic fermented milk drink containing LcS or a placebo was administered. Patients completed a questionnaire to assess the consistency of their stools. In half of the study population, the survival of the probiotic strain (LcS) was tested using (i) culture and (ii) an LcS specific monoclonal antibody to identify the cultured colonies as LcS (ELISA). There was a significant decrease in stool hardening when consuming a fermented milk drink containing LcS. The observed clinical effect went hand in hand with the observed microbiological effect as the number of viable LcS bacteria in the faeces increased when consuming fermented milk drink containing LcS and decreased during wash-out.
Article
The aim of this study was to evaluate the changes in intestinal bifidobacteria and the effect on fecal properties in healthy subjects with mild constipation after administration of a fermented milk containing Bifidobacterium animalis subsp. lactis (B. lactis) GCL2505. Volunteers (n=62 ; 15 male, 47 female ; 42.5±10.2 years [mean±SD]) were randomly divided into two groups and given 100 g of fermented milk containing B. lactis GCL2505 (>1×10 7cfu/g) or a placebo daily for 2 weeks in a double-blind crossover study. An increase in the number of total bifidobacteria (sum of B. bifidum, B. breve, B. longum subsp. longum, B. adolescente, B. angulatum, B. catenulatum, B. pseudocatenulatum, B. dentium, B. longum subsp. infantis, and B. lactis) was detected in feces after administration of the B. lactis GCL2505 fermented milk by species- and subspecies-specific real-time polymerase chain reaction analysis. The number of endogenous bifidobacteria species, excluding B. lactis, remained unchanged, and B. lactis became the predominant bifidobacterial species. Defecation frequency and stool quantity increased significantly (p < 0.05) during the B. lactis GCL2505 fermented milk ingesting period compared with placebo. These results indicate that GCL2505-fermented milk contributes to an increase in intestinal bifidobacteria by proliferating itself and to improvements in mild constipation without affecting endogenous bifidobacteria.
Article
AIM: To investigate the effect of a fermented milk containing Bifidobacterium lactis DN-173010 and yogurt strains (BIO®) on adult women with constipation in Beijing. METHODS: A total of 135 adult females with constipation were randomly allocated to consume for 2 wk either 100 g of the test fermented milk or 100 g of an acidified milk containing non-living bacteria (control). Stool frequency, defecation condition scores, stool consistency and food intake were recorded at baseline and after 1 and 2 wk in an intention-to-treat population of 126 subjects. In parallel, safety evaluation parameters were performed. RESULTS: At baseline, no differences were found between groups. Following consumption of test product, stool frequency was significantly increased after 1 wk (3.5 ± 1.5 vs 2.4 ± 0.6, P < 0.01) and 2 wk (4.1 ± 1.7 vs 2.4 ± 0.6, P < 0.01), vs baseline. Similarly, after 1 and 2 wk, of test product consumption, defecation condition (1.1 ± 0.9 vs 1.9 ± 1.2, P < 0.01 and 0.8 ± 1.0 vs 1.9 ± 1.2, P < 0.01, respectively) and stool consistency (1.0 ± 0.8 vs 1.5 ± 1.1, P < 0.01 and 0.6 ± 0.8 vs 1.5 ± 1.1, P < 0.01, respectively) were significantly improved. Compared with the control group, stool frequency was also significantly increased (3.5 ± 1.5 vs 2.5 ± 0.9, P < 0.01 and 4.1 ± 1.7 vs 2.6 ± 1.0, P < 0.01, respectively), and defecation condition (1.1 ± 0.9 vs 1.6 ± 1.1, P < 0.01 and 0.8 ± 1.0 vs 1.6 ± 1.1, P < 0.01, respectively) and stool consistency (1.0 ± 0.8 vs 1.4 ± 1.0, P < 0.05 and 0.6 ± 0.8 vs 1.3 ± 1.0, P < 0.01, respectively) significantly decreased after 1 and 2 wk of product consumption. During the same period, food intake did not change between the two groups, and safety parameters of the subjects were within normal ranges. CONCLUSION: This study suggests a beneficial effect of a fermented milk containing B. lactis DN-173010 on stool frequency, defecation condition and stool consistency in adult women with constipation constipated women after 1 and 2 wk of consumption.
Article
Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement-a reporting guideline published in 1999-there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (www.prisma-statement.org) should be helpful resources to improve reporting of systematic reviews and meta-analyses.
Article
The effects of bacterial fermentation on human colonic motor activity could be explained by colonic acidification or short-chain fatty acid (SCFA) production. We compared in healthy volunteers the colonic motor effects of intracolonic infusion of neutral or acidic saline solutions and then of neutral or acidic solutions containing an SCFA mixture. 20 healthy volunteers swallowed a probe (with an infusion catheter, 6 perfused catheters and a balloon connected to a barostat) that migrated into the colon. Colonic motor activity was recorded in fasting basal state (1 h), during (3 h) and after (2 h) intracolonic infusion in a random order on two consecutive days of 750 mL of NaCl at pH 7.0 (neutral saline) or 4.5 (acidic saline) in 10 volunteers (first experiment) and of an SCFA mixture (acetic acid 66%, propionic acid 24% and butyric acid 10%; 100 mM) at pH 7.0 or 4.5 in 10 other volunteers (second experiment). We determined for each hour a global motility index (reflecting phasic activity recorded by all catheters), the mean balloon volume (reflecting tonic activity), and the mean number of high-amplitude-propagated contractions (HAPCs). Intracolonic infusion of neutral or acidic solutions containing saline or an SCFA mixture did not change the global motility index, the barostat balloon volume, or the HAPC number compared with basal values. Under our experimental conditions, these findings suggest that the stimulation of colonic motor activity induced by carbohydrate fermentation is not explained by the acidification of the colonic contents or the resulting production of SCFAs.
Article
& Aims: Patients with irritable bowel syndrome with constipation (IBS-C) and patients with functional constipation (FC) have similar symptoms, and these disorders overlap in their diagnostic features. Little is known about their overlap in physiology or the involvement of serotonin signaling. We investigated relationships between platelet-depleted plasma concentrations of serotonin, gastrointestinal symptoms, and motor-sensory function in patients with FC or IBS-C compared with healthy volunteers (controls) METHODS: We measured platelet-depleted plasma concentrations of serotonin in fasting and fed individuals with IBS-C (n=23, 19-50 y old) or FC (n=11, 25-46 y old) and controls (n=23, 20-49 y old), recruited in Manchester, UK. We also quantified abdominal and bowel-related symptoms, rectal sensitivity, oro-cecal transit, and colonic (whole intestine) transit. Patients with IBS-C or FC had similar baseline symptoms, bowel habits, oro-cecal and colonic transit, and fasting concentrations of serotonin and response to meal ingestion. Only patients with IBS-C had increased symptoms following ingestion of a meal (P<.001)-these patients tended to have lower sensory thresholds than patients with FC. Defecation frequency in the combined group of patients with IBS-C or FC correlated inversely with serotonin concentration (r = -0.4; P=.03). Serotonin concentration also correlated with pain threshold (r = 0.4; P=.02) and stool threshold (r = 0.5; P=.06), which correlated inversely with defecation frequency (r = -0.3; P=.10). FC and IBS-C, based on Rome III criteria, are not distinct disorders, symptomatically or physiologically. Instead, they appear to lie in a spectrum of visceral sensitivity modulated by serotonin signaling. Symptom response to meal ingestion should be considered in patient classification.
Article
Evidence suggests that probiotics reduce certain constipation-related symptoms. Lactobacillus casei strain Shirota has never been tested as treatment for functional constipation in otherwise-healthy subjects. To evaluate the efficacy of this probiotic among adults with functional constipation was aimed. Subjects with functional constipation (Rome II-defined) were randomized to intake L. casei strain Shirota fermented milk or placebo once daily for 4 weeks under double-blind condition. Primary outcomes were constipation severity and stool frequency; secondary outcomes were stool consistency and quantity. In intent-to-treat population, compared with baseline, constipation severity and stool frequency improved in both probiotic (n = 47) and control groups (n = 43), but improvements were comparable in both groups at week 4 (α = 5% level). In probiotic group, stool consistency and quantity at week 4 improved significantly versus baseline but not versus control. Considering that the study agent is non-pharmaceutical and the purpose of supplementation is for long-term effect, re-evaluation at α = 10% was conducted, which showed significant improvement in constipation severity at week 4 (P = 0.058). Magnitude of the probiotic effect on stool consistency was small but grew over time, d = 0.19, 95% confidence interval 0.00–0.35 (Week 4), d = 0.29, 95% confidence interval 0.11–0.52 (postintervention). Post-hoc exploratory analysis suggests incomplete evacuation may decrease with probiotic intake. Four-week administration of L. casei strain Shirota did not alleviate constipation severity or stool frequency, consistency, and quantity when compared with control. With re-evaluation at α = 10% level, improvement in constipation severity was significant at week 4. To obtain conclusive results, further studies with longer intervention are warranted.
Article
Background & aims: Diet has major effects on the intestinal microbiota, but the exact mechanisms that alter complex microbial communities have been difficult to elucidate. In addition to the direct influence that diet exerts on microbes, changes in microbiota composition and function can alter host functions such as gastrointestinal (GI) transit time, which in turn can further affect the microbiota. Methods: We investigated the relationships among diet, GI motility, and the intestinal microbiota using mice that are germ-free (GF) or humanized (ex-GF mice colonized with human fecal microbiota). Results: Analysis of gut motility revealed that humanized mice fed a standard polysaccharide-rich diet had faster GI transit and increased colonic contractility compared with GF mice. Humanized mice with faster transit due to administration of polyethylene glycol or a nonfermentable cellulose-based diet had similar changes in gut microbiota composition, indicating that diet can modify GI transit, which then affects the composition of the microbial community. However, altered transit in mice fed a diet of fermentable fructooligosaccharide indicates that diet can change gut microbial function, which can affect GI transit. Conclusions: Based on studies in humanized mice, diet can affect GI transit through microbiota-dependent or microbiota-independent pathways, depending on the type of dietary change. The effect of the microbiota on transit largely depends on the amount and type (fermentable vs nonfermentable) of polysaccharides present in the diet. These results have implications for disorders that affect GI transit and gut microbial communities, including irritable bowel syndrome and inflammatory bowel disease.
Book
The Cochrane Handbook for Systematic Reviews of Interventions (the Handbook) has undergone a substantial update, and Version 5 of the Handbook is now available online at www.cochrane-handbook.org and in RevMan 5. In addition, for the first time, the Handbook will soon be available as a printed volume, published by Wiley-Blackwell. We are anticipating release of this at the Colloquium in Freiburg. Version 5 of the Handbook describes the new methods available in RevMan 5, as well as containing extensive guidance on all aspects of Cochrane review methodology. It has a new structure, with 22 chapters divided into three parts. Part 1, relevant to all reviews, introduces Cochrane reviews, covering their planning and preparation, and their maintenance and updating, and ends with a guide to the contents of a Cochrane protocol and review. Part 2, relevant to all reviews, provides general methodological guidance on preparing reviews, covering question development, eligibility criteria, searching, collecting data, within-study bias (including completion of the Risk of Bias table), analysing data, reporting bias, presenting and interpreting results (including Summary of Findings tables). Part 3 addresses special topics that will be relevant to some, but not all, reviews, including particular considerations in addressing adverse effects, meta-analysis with non-standard study designs and using individual participant data. This part has new chapters on incorporating economic evaluations, non-randomized studies, qualitative research, patient-reported outcomes in reviews, prospective meta-analysis, reviews in health promotion and public health, and the new review type of overviews of reviews.
Article
Background Slow-transit constipation (STC) is caused by a motility disorder of the colon which leads to delayed transit (>72 h). The probiotic strain Lactobacillus casei Shirota (LcS) has been shown to improve constipation-related symptoms, such as stool frequency and consistency. A randomized double-blind placebo-controlled trial was performed to determine the effect of LcS on the colonic transit time in patients with STC. Patients and methods Colonic transit time of all consecutive outpatients with chronic constipation was determined by the Hinton test using radiopaque markers. Patients with a transit time longer than 72 h were included in the study. A total of 24 patients received either a dairy drink containing 6.5×109 colony forming units (cfu) of LcS or a placebo daily for 4 weeks. General gastrointestinal symptoms were evaluated weekly by a questionnaire and the measurement of colonic transit time was repeated after the intervention. Results The intake of LcS resulted in a significant acceleration of the total colonic transit time from 95.6 h to 76.5 h (p=0.05). This effect was most pronounced in the sigmoid and rectum transit time (p<0.007). In the placebo group no statistically significant change in the total colonic transit time was observed (before: 95.8 h, after: 87.1 h, p=0.282) Conclusion The daily intake of a probiotic drink containing LcS significantly reduced the colonic transit time in patients with STC.
Article
The aim of this study was to evaluate the changes in endogenous bifidobacteria and administered Bifidobacterium animalis subsp. lactis (B. lactis) GCL2505 (GCL2505) in the intestine after administration of GCL2505 by means of a randomized, placebo-controlled double-blind, cross-over study. An increase in the number of total bifidobacteria (the sum of B. bifidum, B. breve, B. longum subsp. longum, B. adolescentis, B. anglatum, B. catenulatum, B. pseudocatenulatum, B. dentium, B. longum subsp. infantis and B. lactis) in the feces were observed after administration of GCL2505 using species- and subspecies-specific real-time polymerase chain reaction analysis. However, the number of endogenous bifidobacteria species (excluding B. lactis) remained unchanged. B. lactis also became the predominant bifidobacterial species. Taking into account the number of GCL2505 administered, the findings further suggested that GCL2505 proliferated in the intestine. In addition, the defecation frequency increased during GCL2505 administration compared with the placebo. Moreover, a single administration study (n=17) clearly demonstrated that GCL2505 successfully reached the intestine before proliferating at least 10-fold. This is the first report to show an increase in intestinal bifidobacteria, with no changes to the endogenous species, and improvements in constipation following proliferation of administered bifidobacteria.
Article
The role of probiotics in the management of constipation is uncertain. To evaluate the effects of probiotic-enriched artichokes on treatment preference, symptom profile and short-chain fatty acid (SCFA) production in constipated subjects when compared with ordinary artichokes. Twenty constipated patients (3M/17F; 38.8 ± 14.4 years) were studied using a double-blind method and a computer-generated randomisation list. Each patient consumed 180 g per day of ordinary artichokes or artichokes enriched with Lactobacillus paracasei IMPC 2.1 for 15 days (daily dose of 2 × 10(10) CFU). Relief of symptoms was evaluated using a visual analogue scale. The stool consistency and symptom profile of patients were investigated using the Bristol stool form chart and the Gastrointestinal Symptom Rating Scale questionnaire (GSRS). SCFA production in faecal samples was evaluated using HPLC. Eighty per cent of patients preferred probiotic-enriched artichokes to ordinary ones (P = 0.011). Satisfactory relief of symptoms was significantly higher (P = 0.0014) during the probiotic-enriched artichoke period. Bristol chart cluster scores were significantly higher (3.3 ± 1.2, 2.9 ± 1.3 2.2 ± 1.2, baseline, ordinary artichokes and probiotic-enriched ones, respectively; P = 0.009) and GSRS constipation was significantly lower (13.9 ± 0.9, 10.2 ± 0.8, 8.3 ± 0.9; P = 0.032) in the probiotic group compared with the baseline. As for SCFA production, propionic acid was significantly higher (2.2 ± 1.4, 2.1 ± 1.53, 1.5 ± 1.2; P = 0.035) in the probiotic group compared with baseline. This trial shows a positive effect on symptoms in constipated patients after intake of probiotic-enriched artichokes.
Article
Evacuation disorders and hard stools are common in industrialized countries, affecting on average 12% to 17% of the adult healthy population at any age. Dietary supplementation with probiotic microorganisms may be useful in reducing the disorder. We performed a double-blind, randomized, placebo-controlled study to evaluate the effectiveness of 2 different probiotic blends, either mixed Lactobacillus plantarum LP01 (LMG P-21021) and Bifidobacterium breve BR03 (DSM 16604) or Bifidobacterium animalis subspecies lactis BS01 (LMG P-21384), in the management of evacuation disorders and intestinal discomfort. In a period of 5 years (2003 to 2008), the study involved 300 healthy volunteers (151 males and 149 females; age 24 to 71 y) with evacuation disorders and hard stools. In particular, subjects were divided into 3 groups: 80 subjects in the group A received placebo, 110 subjects in the group B received mixed L. plantarum LP01 and B. breve BR03 (2.5 x 10 colony-forming units/d of each strain), and 110 subjects in the group C received B. animalis subsp. lactis BS01 (5 x 10 colony-forming units/d) for 30 days. At the beginning of the observational study, the healthy status of volunteers was evaluated by a complete, laboratory and ultrasound study of the abdomen. The physical examination was repeated after 15 and 30 days. In particular, the main troubles typically associated with evacuation disorders and hard stools as well as abdominal bloating were considered as parameters of interest. Exclusion criteria were items of gastrointestinal diseases and antibiotics intake. Subjects treated with the mixed probiotic strains L. plantarum LP01 and B. breve BR03 or B. animalis subsp. lactis BS01 reported a significant improvement in the number of weekly bowel movements and in the main troubles associated with evacuations, particularly consistency of feces and ease of expulsion. Discomfort items such as abdominal bloating and anal itching, burning, or pain also registered a relevant improvement in the active groups receiving probiotics. The intake of an effective amount of mixed L. plantarum LP01 and B. breve BR03 or B. animalis subsp. lactis BS01 for 30 days is able to significantly relieve the evacuation disorders and hard stools, thus providing a useful tool for the management of such condition, which is particularly widespread in industrialized countries at any age.
Article
The Rome III classification system treats functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) as distinct disorders, but this distinction appears artificial, and the same drugs are used to treat both. This study's hypothesis is that FC and IBS-C defined by Rome III are not distinct entities. In all, 1,100 adults with a primary care visit for constipation and 1,700 age- and gender-matched controls from a health maintenance organization completed surveys 12 months apart; 66.2% returned the first questionnaire. Rome III criteria identified 231 with FC and 201 with IBS-C. The second survey was completed by 195 of the FC and 141 of the IBS-C cohorts. Both surveys assessed the severity of constipation and IBS, quality of life (QOL), and psychological distress. (i) Overlap: if the Rome III requirement that patients meeting criteria for IBS cannot be diagnosed with FC is suspended, 89.5% of IBS-C cases meet criteria for FC and 43.8% of FC patients fulfill criteria for IBS-C. (ii) No qualitative differences between FC and IBS-C: 44.8% of FC patients report abdominal pain, and paradoxically IBS-C patients have more constipation symptoms than FC. (iii) Switching between diagnoses: by 12 months, 1/3 of FC transition to IBS-C and 1/3 of IBS-C change to FC. Patients identified by Rome III criteria for FC and IBS-C are not distinct groups. Revisions to the Rome III criteria, possibly including incorporation of physiological tests of transit and pelvic floor function, are needed.
Article
To systematically evaluate and update evidence on the efficacy and safety of probiotic supplementation for the treatment of constipation. The MEDLINE, EMBASE, CINAHL, and Cochrane Library databases were searched in May 2009 for randomised controlled trials (RCTs) performed in paediatric or adult populations related to the study aim. We included five RCTs with a total of 377 subjects (194 in the experimental group and 183 in the control group). The participants were adults (three RCTs, n = 266) and children (two RCTs, n = 111) with constipation. In adults, data suggests a favourable effect of treatment with Bifidobacterium lactis DN-173 010, Lactobacillus casei Shirota, and Escherichia coli Nissle 1917 on defecation frequency and stool consistency. In children, L. casei rhamnosus Lcr35, but not L. rhamnosus GG, showed a beneficial effect. Until more data are available, we believe the use of probiotics for the treatment of constipation condition should be considered investigational.
Article
Accurate information on harms of medical interventions is essential for evidence-based practice. Most newly introduced treatments usually have small, incremental benefits, if any, against already available interventions, and differences in the profile of harms should play a key role on treatment choice. Randomized trials offer an excellent opportunity to evaluate harms of interventions using the most robust experimental design available in clinical research. However, several empirical evaluations (Table) have shown that many trials do not report harms or report them in a fragmented or suboptimal way. In this issue, an excellent study by Pitrou et al1 adds more evidence on this issue.
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Chronic constipation is one of the most frequent complaints in childhood. Although there is evidence that gastrointestinal flora is important in gut motility, there is little evidence that gut flora is abnormal in constipation. Lactobacilli and bifidobacteria increase stool frequency and decrease consistency in normal individuals. But, according to several reviews, the evidence of probiotics for efficacy in constipation is limited. Fiber supplements, lactose-free diets, and lactobacillus supplementation are effective in the management of children with recurrent abdominal pain and irritable bowel syndrome. Several studies with Lactobacillus GG in children showed negative results in children with chronic constipation. Because Bifidobacterium animalis DN-173 010 has been shown to be effective in adults with constipation-predominant irritable bowel syndrome this study should also be performed in a well-designed large placebo-controlled trial in children with constipation.
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Introduction to the Everhart SeriesDigestive, liver, and pancreatic diseases have a far-reaching medical, economic, social, and political impact on society in the United States and worldwide. We believe it is important to highlight salient features as well as key tables/figures from the report that was commissioned by the National Institutes of Health on the burden of digestive, liver, and pancreatic diseases in the United States. Divided into three segments, this series, spanning consecutive issues Gastroenterology, will be informative and illuminating. The series will provide investigators, clinicians, and other readers with the necessary tools to generate new hypotheses, craft new directions of broad-based and integrated research, and make informed clinical conclusions. Hashem B. El-Serag, Anil K. Rustgi.
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To investigate the effect of a fermented milk containing Bifidobacterium lactis DN-173010 and yogurt strains (BIO(R)) on adult women with constipation in Beijing. A total of 135 adult females with constipation were randomly allocated to consume for 2 wk either 100 g of the test fermented milk or 100 g of an acidified milk containing non-living bacteria (control). Stool frequency, defecation condition scores, stool consistency and food intake were recorded at baseline and after 1 and 2 wk in an intention-to-treat population of 126 subjects. In parallel, safety evaluation parameters were performed. At baseline, no differences were found between groups. Following consumption of test product, stool frequency was significantly increased after 1 wk (3.5 +/- 1.5 vs 2.4 +/- 0.6, P < 0.01) and 2 wk (4.1 +/- 1.7 vs 2.4 +/- 0.6, P < 0.01), vs baseline. Similarly, after 1 and 2 wk, of test product consumption, defecation condition (1.1 +/- 0.9 vs 1.9 +/- 1.2, P < 0.01 and 0.8 +/- 1.0 vs 1.9 +/- 1.2, P < 0.01, respectively) and stool consistency (1.0 +/- 0.8 vs 1.5 +/- 1.1, P < 0.01 and 0.6 +/- 0.8 vs 1.5 +/- 1.1, P < 0.01, respectively) were significantly improved. Compared with the control group, stool frequency was also significantly increased (3.5 +/- 1.5 vs 2.5 +/- 0.9, P < 0.01 and 4.1 +/- 1.7 vs 2.6 +/- 1.0, P < 0.01, respectively), and defecation condition (1.1 +/- 0.9 vs 1.6 +/- 1.1, P < 0.01 and 0.8 +/- 1.0 vs 1.6 +/- 1.1, P < 0.01, respectively) and stool consistency (1.0 +/- 0.8 vs 1.4 +/- 1.0, P < 0.05 and 0.6 +/- 0.8 vs 1.3 +/- 1.0, P < 0.01, respectively) significantly decreased after 1 and 2 wk of product consumption. During the same period, food intake did not change between the two groups, and safety parameters of the subjects were within normal ranges. This study suggests a beneficial effect of a fermented milk containing B. lactis DN-173010 on stool frequency, defecation condition and stool consistency in adult women with constipation constipated women after 1 and 2 wk of consumption.
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The contractile effect of short-chain fatty acids on proximal, middle and distal segments of the rat colon was studied in vitro. A single contraction of the longitudinal muscle of the everted preparation of the middle and distal but not the proximal colon was induced by mucosal application of propionate, butyrate or valerate. Sigmoid dose-responses were observed between contraction and log dose of propionate, butyrate and valerate. The threshold concentration of short-chain fatty acids was between 0.02 and 0.04 mM. A maximal contraction was induced with 0.1 mM-propionate, butyrate and valerate. While acetate (up to 10 mM) and lactate (up to 30 mM) had no contractile effect at all. Serosal application of short-chain fatty acids was without effect, while the contractile response with up to 10 mM-propionate was abolished in both the middle and distal colon by scraping away the mucosa. Cumulative addition of short-chain fatty acids to the organ bath (without wash-out of the first dose) caused adaptation of the contractile response; thus, the effect of propionate (1 mM) was abolished by prior addition of acetate (10 mM) or lactate (30 mM) or propionate (1 mM) or butyrate (1 mM) or valerate (1 mM). The contractile effect of propionate was also inhibited by atropine (1 microM), procaine (0.4 mM) and tetrodotoxin (3 microM); was unaffected by hexamethonium (0.1 mM) and enhanced by eserine (10 nM). The results suggest that short-chain fatty acids, which are normal constituents of the colon, have the ability to stimulate colonic contractions, probably via an enteric reflex involving local sensory and cholinergic nerves.
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A randomized, double-blind clinical trial including a change-over of medication was carried out for 9 weeks to investigate the efficacy of an E. coli preparation. The study's main objective was to prove that patients of the verum group had 1.5 stools/week more than placebo patients after a therapeutic period of just 4 weeks. Stool consistency as well as efficacy and compatibility of the medication as judged by doctor and patient were additional criteria. For a 7-day run-in phase 134 patients were recruited who had suffered from constipation for 18.8 years in average. In this initial phase 64 patients evacuated more than 2 stools per week and were excluded from the study. The remaining 70 patients entered the therapeutic phase being randomly distributed amongst verum and placebo medication. After 4 weeks of therapy patients who delivered 2 or less stools/week obtained the alternative medication (change-over). Within the 4th week of therapy the average number of stools per week from patients treated with the E. coli preparation (4.9) was already significantly higher than from placebo-treated patients (2.6; p < 0.001). At the end of the 8th week of therapy the number of stools/week rose to 6.0 for verum-treated patients, whereas for the placebo-treated control group a decrease in stool frequency was observed (1.9 stools/week). The results of change-over patients confirmed the data of the therapy weeks 1 to 4. The E. coli preparation proved to be successful in the therapy of the idiopathic chronic constipation almost free of side effects.
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During the fermentation of lactulose, short-chain fatty acids are formed with consequent lowering of the colon pH and modification of the microflora. Lactulose promotes the growth of lactic acid bacteria and bifidobacteria and, more specifically, Lactobacillus acidophilus in the colon. Lactulose and lactulose-containing products fermented with lactic acid bacteria lower colonic pH balancing intestinal microecology and normalizing intestinal transit. In animal studies, lactulose promotes a mainly Gram-positive faecal microflora, but large doses of lactulose may be associated with transient diarrhoea. Our studies indicate that lactulose with lactic acid bacteria effectively relieves constipation in human volunteers. Lactulose with lactic acid bacteria in a fermented diary product can balance and prevent radiotherapy-associated diarrhoea and intestinal side effects. Normalizing the intestinal flora and stabilizing mucosal integrity with lactulose has beneficial effects in intestinal disorders. Lactulose and lactic acid bacteria offer a promising ingredient combination for future functional and special dietary foods in treating intestinal disturbances.
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Little information is available about the health-related quality of life (QoL) in patients with different types of chronic constipation. We used two self-administered questionnaires, the Psychological General Well-Being (PGWB) index and the Gastrointestinal Symptom Rating Scale (GSRS) to assess QoL and gastrointestinal symptoms in 102 consecutive patients with chronic constipation. The type of constipation was determined from transit time, electrophysiologic investigation of sphincter function, anorectal manometry, and defecography. Overall, our patients with constipation reported low scores for general well-being (mean score, 85.5, compared with 102.9 in a healthy population). Patients with normal-transit constipation (n = 49) reported considerably lower scores in the PGWB than those with slow-transit constipation (n = 35). The symptoms increased frequency of defecation, loose stools, and urgent need for defecation were commoner in normal-transit constipation, which indicates that this group may have a relation to the irritable bowel syndrome. The overall PGWB index was strongly correlated with the total GSRS (P < 0.001). The general well-being of patients with chronic constipation is lower than that of a comparable normal population. Symptom severity correlates negatively with perceived quality of life.