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Randomised clinical trial: Gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome

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Abstract

BackgroundA low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet can ameliorate symptoms in adult irritable bowel syndrome (IBS) within 48 h.AimTo determine the efficacy of a low FODMAP diet in childhood IBS and whether gut microbial composition and/or metabolic capacity are associated with its efficacy.Methods In a double-blind, crossover trial, children with Rome III IBS completed a 1-week baseline period. They then were randomised to a low FODMAP diet or typical American childhood diet (TACD), followed by a 5-day washout period before crossing over to the other diet. GI symptoms were assessed with abdominal pain frequency being the primary outcome. Baseline gut microbial composition (16S rRNA sequencing) and metabolic capacity (PICRUSt) were determined. Metagenomic biomarker discovery (LEfSe) compared Responders (≥50% decrease in abdominal pain frequency on low FODMAP diet only) vs. Nonresponders (no improvement during either intervention).ResultsThirty-three children completed the study. Less abdominal pain occurred during the low FODMAP diet vs. TACD [1.1 ± 0.2 (SEM) episodes/day vs. 1.7 ± 0.4, P < 0.05]. Compared to baseline (1.4 ± 0.2), children had fewer daily abdominal pain episodes during the low FODMAP diet (P < 0.01) but more episodes during the TACD (P < 0.01). Responders were enriched at baseline in taxa with known greater saccharolytic metabolic capacity (e.g. Bacteroides, Ruminococcaceae, Faecalibacterium prausnitzii) and three Kyoto Encyclopedia of Genes and Genomes orthologues, of which two relate to carbohydrate metabolism.Conclusions In childhood IBS, a low FODMAP diet decreases abdominal pain frequency. Gut microbiome biomarkers may be associated with low FODMAP diet efficacy.ClinicalTrials.gov identifier: NCT01339117.

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... A 2017 updated Cochrane systematic review [3] found only one short-term (2 days), double-blind, cross-over, randomized controlled trial (RCT) investigating use of a low-FODMAP diet in children with IBS (n = 33) [9]. The authors reported fewer episodes of abdominal pain per day and no adverse events after 2 days of a low-FODMAP diet compared with both a traditional American childhood diet and the baseline value. ...
... The start of the recruitment is planned in September 2020 and should be completed over 24 months. For study recruitment in a similar single-center study with similar eligibility criteria [9], 28 months was a sufficient period. ...
... Inclusion criteria At enrollment, the volunteer children must fulfill all of the following eligibility criteria to be considered for inclusion: (1) age at least 8 years and ≤ 18 years (regardless of race, ethnicity, gender); (2) FAP-NOS or IBS diagnosed according to the Rome IV Criteria [2]; (3) baseline average pain intensity at least 30 mm on a 100-mm Visual Analogue Scale (VAS) [9]; (4) feeding via the oral route; (5) ability to read and comprehend any employed questionnaires/scales; (6) signed informed consent; and (7) stated availability throughout the study period. ...
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Background: Evidence from studies in adults documents that fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may be triggers of symptoms in individuals with functional abdominal pain disorders (FAPDs). However, in children, the evidence is very limited. We aim to assess the effects of a low-FODMAP diet compared with a regular diet for the management of children with FAPDs. Methods: We will perform a randomized, quadruple-blinded, controlled trial. Seventy-four children aged 8 to 18 years with a FAPD (Irritable Bowel Syndrome or Functional Abdominal Pain-Not Otherwise Specified), diagnosed according to the Rome IV criteria, will be randomly allocated to receive either a low-FODMAP diet or a regular diet for 4 weeks. The primary outcome will be the percentage of the responders, defined as the participants who have at least 30% improvement in abdominal pain intensity on a Visual Analogue Scale (VAS) during the last week of the trial compared with baseline, that is at least equal to the Reliable Change Index (≥ 25 mm change on VAS). Other outcomes will include changes in stool consistency, abdominal pain frequency, total scores on the Gastrointestinal Symptom Rating Scale, KIDSCREEN-10 Index and World Health Organization Five Well-Being Index, child's school attendance and parents' work absenteeism, and BMI-for-age z-score. Compliance, tolerability of the low-FODMAP diet, and adverse events also will be evaluated. Each FAPD subtype will be assessed separately. Discussion: There is a need for high-quality evidence regarding the dietary management of children with FAPDs. This randomized controlled trial (RCT) of rigorous methodological design will help to establish the effectiveness, if any, of a low-FODMAP diet for the management of FAPDs in the pediatric population. The findings of this RCT will assist with the development of guidelines and influence the direction of further research. Trial registration: NCT04528914 Data and protocol version identifier: 24/08/2020.
... Authors of ongoing trials were contacted. Finally, 12 articles were included for analysis [44][45][46][47][48][49][50][51][52][53][54][55]. Data of 819 FAPD patients aged 4-18 years, with the majority suffering from IBS, were included for analysis. ...
... Period of follow-up ranged from no follow-up after end of intervention to 4 weeks. Five trials evaluated treatment with fibers compared to placebo [44,45,48,49,54], two trials investigated a diet low in FODMAPs [50,55]. Remaining studies determined whether fructans worsen symptoms [51], studied fructose-restricted diet [46], evaluated treatment with prebiotic (inulin) [47], compared oral serum-derived bovine immunoglobulin (SBI) versus placebo [52], and vitamin D supplementation [53]. ...
... In the study of Chumpitazi et al., it was not clear if the type of food or drink provided during interventions was similar (performance bias). Second, since it was a cross-over study and washout period was only 5 days, the carry over effect could not be excluded [55]. Furthermore, 6 of the 12 studies (50%) were rated as having unclear risk of bias in at least one domain as a result of inadequate reporting [44][45][46][50][51][52]. ...
Article
Background: Functional abdominal pain disorders (FAPDs) are common among children and are associated with decreased quality of life and school attendance. Several dietary interventions have been suggested to improve symptoms of FAPDs. This systematic review assessed the efficacy and safety of dietary interventions for pediatric FAPDs. Design and methods: Electronic databases were searched from inception to October 2021. Systematic reviews or RCTs were included if children (4-18 years) with FAPDs were treated with dietary interventions and compared to placebo, no diet or any other diet. Data extraction and assessment of quality of evidence based on GRADE system was independently performed by two review authors. Outcomes were treatment success, pain intensity and frequency, and withdrawal due to adverse events. Results: Twelve articles were included, representing data of 819 pediatric FAPD patients. Trials investigating fibers, FODMAP diet, fructans, fructose restricted diet, prebiotic (inulin), serum-derived bovine immunoglobulin and vitamin D supplementation were included. We found very low-certainty evidence that the use of fibers leads to higher treatment success (NNT=5). Conclusion: Based on the current evidence, the use of fibers can be discussed in daily practice. High-quality intervention trials are highly needed to investigate if other dietary interventions are effective in the treatment of pediatric FAPD.
... FODMAPs are poorly absorbable carbohydrates that exert an osmotic load on the gut, and are rapidly fermented by colonic bacteria, resulting in gas production causing abdominal distention, bloating, and pain (7). A low FODMAP diet has been shown to improve IBS symptoms (8)(9)(10)(11)(12)(13)(14)(15)(16) and is currently the dietary factor with most evidence as a regimen for IBS (6). However, many FODMAP restriction studies suffer from suboptimal design, being no or single-blind (8)(9)(10)(11)(12)(13)(14)(15). ...
... However, many FODMAP restriction studies suffer from suboptimal design, being no or single-blind (8)(9)(10)(11)(12)(13)(14)(15). In fact, only 1 double-blind study with a low FODMAP diet has been conducted and was carried out in children (16). Furthermore, most studies have focused on the elimination of FODMAPs from the diet, rather than provocation (8)(9)(10)(11)(12)(13)(14)(15)(16). ...
... In fact, only 1 double-blind study with a low FODMAP diet has been conducted and was carried out in children (16). Furthermore, most studies have focused on the elimination of FODMAPs from the diet, rather than provocation (8)(9)(10)(11)(12)(13)(14)(15)(16). A few studies, all single-blind, have employed provocations using all FODMAP components (12,17), though similar double-blind studies have used provocations with only a few FODMAPs (18)(19)(20)(21). ...
Article
Background Irritable bowel syndrome (IBS) has been associated with diets rich in fermentable oligo-, di-, monosaccharides and polyols (FODMAPs), and gluten. Most previous studies have been single-blind and have focused on elimination of FODMAPs or provocation with single FODMAPs. The effect of gluten is unclear, large trials isolating the effect of gluten from that of FODMAPs are needed. Objective The aims of this study were to ensure high intakes of a wide range of FODMAPs, gluten, or placebo, and to evaluate the effects on IBS symptoms using the IBS severity scoring system (IBS-SSS). Methods The study was carried out with a double-blind, placebo-controlled, randomized three-way crossover design in a clinical facility in Uppsala in September 2018—June 2019. In all, 110 participants fulfilling the IBS Rome IV criteria, with moderate to severe IBS, were randomized; 103 (90 female, 13 male) completed the trial. Throughout, IBS participants maintained a diet with minimal FODMAP content and no gluten. Participants were block-randomized to one-week interventions with FODMAPs (50 g/day), gluten (17.3 g/day), or placebo, separated by one week washout. All participants who completed at least one intervention were included in the intention-to-treat analysis. Results In participants with IBS (n = 103), FODMAPs caused higher IBS-SSS scores (mean 240 [95% CI 222, 257]) than placebo (198 [180, 215]; 0.00056) or gluten (208 [190, 226]; P = 0.013); no differences were found between the placebo and gluten groups (P = 1.0). There were large inter-individual differences in IBS-SSS scores associated with treatment. No adverse events were reported. Conclusion In participants with IBS, FODMAPs had a modest effect on typical IBS symptoms, whereas gluten had no effect. The large inter-individual differences in responses to the interventions warrant further detailed studies to identify possible underlying causes and enable individual prediction of responses. Trial registration www.ClinicalTrials.gov (NCT03653689).
... Four full-length papers 16,17,29,30 and one abstract 31 (preliminary results) were included (153 participants) ( Table 1). ...
... Sample size calculations were reported in three RCTs. 17,29,30 Two trials 29,30 were conducted in USA (40%), one in Poland, 16 one in Singapore, 31 and one in Turkey. 17 Three of the five RCTs (60%) were of cross-over design [29][30][31] and two 16,17 had two parallel arms. ...
... Sample size calculations were reported in three RCTs. 17,29,30 Two trials 29,30 were conducted in USA (40%), one in Poland, 16 one in Singapore, 31 and one in Turkey. 17 Three of the five RCTs (60%) were of cross-over design [29][30][31] and two 16,17 had two parallel arms. ...
Article
Background: Evidence for the management of pediatric functional abdominal pain disorders (FAPD) is lacking. The aim of this systematic review was to update evidence on the efficacy and safety of implementing low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) dietary restrictions for the management of children with FAPD. Methods: The Cochrane Library, EMBASE, and MEDLINE databases were searched up to October 2021 for randomized controlled trials (RCTs) that compared the use of a low-FODMAP diet with any comparator in children aged 3-18 years with FAPD. The primary outcome was abdominal pain intensity. Key results: Five RCTs assessing the effects of a low-FODMAP diet were included. An effect of a low-FODMAP diet on abdominal pain intensity was only found in two trials. In one trial, there was a decrease in abdominal pain intensity on a 0-10 point Visual Analogue Scale (VAS) between low-FODMAP and gastrointestinal protective diet groups after 2 months (mean difference, MD 1.77, 95% confidence interval, CI, 1.23 to 2.31, n = 60). In another trial, there was a difference in abdominal pain intensity during the 3-day intervention between the low-FODMAP and typical Singaporean diet groups (MD -1.36 cm, 95% CI -2.38 to -0.34, n = 10) measured using a 0-10 cm VAS. Conclusions & interferences: There is insufficient evidence for or against the efficacy and safety of using a low-FODMAP diet for the management of children with FAPD.
... Ob diese Ursache oder Folge des RDS sind, bleibt noch unklar [794]. Möglicherweise spielen Mikrobiom-Signaturen eine Rolle beim Ansprechen auf spezifische Diäten [795]. ...
... Auch wenn es erste Hinweise auf Veränderungen des Darmmikrobioms bei Kindern und Jugendlichen mit RDS gibt [793,795], reicht die Evidenz nicht zu einer Empfehlung, insbesondere aufgrund schwieriger Interpretation und fehlender therapeutischer Konsequenz. ...
... Im Vergleich zur Normalnahrung zu Hause (1,4 ± 0,2), hatten die Kinder weniger Bauchschmerzepisoden, während die typische amerikanische Kost zu mehr Beschwerdeepisoden führte. Parallel wurden Veränderungen der Dickdarmmikrobiota bei den Respondern gefunden [795]. Aufgrund der geringen Fallzahl und der sehr kurzen Interventionsperioden und Beobachtungszeiträume reicht die Evidenz nicht zu einer Empfehlung aus. ...
... 11 One potential mechanistic factor garnering increasing attention is the gut microbiome: in both children and adults with IBS, an individual's gut microbiome composition is associated with symptom improvement on a low FODMAP diet. 12,13 In addition, gut microbiome changes (decreased Bifidobacterium abundance) occur in response to a low FODMAP diet. 6,14 Given the growing data related to the gut microbiome and symptoms in response to fermentable carbohydrate, we sought to determine whether gut microbiome composition and function are associated with fructan-induced symptoms. ...
... 31 As used in our previous work and followed by others in the field, we used both a logarithmic Linear Discriminant Analysis (LDA) log 10 threshold of 2.0 and alpha value of 0.05 for the factorial Kruskal-Wallis test for identification of discriminative taxonomic features. 12,31 Only LEfSe discriminative features found in greater than 20% of the analysed samples were reported. IBM SPSS version 25 was used to compare baseline diet components (Mann-Whitney U) between fructan-sensitive vs -tolerant participants (Table 1). ...
... The potential role of the gut microbiome in childhood IBS and as a mechanism by which FODMAP carbohydrates such as fructans induce symptoms in those with functional bowel disorders has garnered increasing attention. 12,13,32 Our study findings suggest fructan-sensitive children differ from fructan-tolerant children with IBS with respect to their baseline gut microbiome alpha and beta di- given the lack of human intestinal tract hydrolases and their associated colonic bifidogenic effect. 8 Many species of bifidobacteria are capable of metabolising fructans and have higher growth rates on fructans rather than monomeric (eg glucose) constituents. ...
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Background: Dietary fructans may worsen gastrointestinal symptoms in children with irritable bowel syndrome (IBS). Aim: To determine whether gut microbiome composition and function are associated with childhood IBS fructan-induced symptoms. Methods: Faecal samples were collected from 38 children aged 7-17 years with paediatric Rome III IBS, who previously completied a double-blind, randomised, placebo-controlled crossover (fructan vs maltodextrin) trial. Fructan sensitivity was defined as an increase of ≥30% in abdominal pain frequency during the fructan diet. Gut microbial composition was determined via 16Sv4 rDNA sequencing. LEfSe evaluated taxonomic composition differences. Tax4Fun2 predicted microbial fructan metabolic pathways. Results: At baseline, 17 fructan-sensitive (vs 21 fructan-tolerant) subjects had lower alpha diversity (q < 0.05) and were enriched in the genus Holdermania. In contrast, fructan-tolerant subjects were enriched in 14 genera from the class Clostridia. During the fructan diet, fructan-sensitive (vs tolerant) subjects were enriched in both Agathobacter (P = 0.02) and Cyanobacteria (P = 0.0001). In contrast, fructan-tolerant subjects were enriched in three genera from the Clostridia class. Comparing the fructan vs maltodextrin diet, fructan-sensitive subjects had a significantly increased relative abundance of Bifidobacterium (P = 0.02) while fructan-tolerant subjects had increased Anaerostipes (P = 0.03) during the fructan diet. Only fructan-sensitive subjects had a trend towards increased predicted β-fructofuranosidase during the fructan vs maltodextrin diet. Conclusions: Fructan-sensitive children with IBS have distinct gut microbiome signatures. These microbiome signatures differ both at baseline and in response to a fructan challenge.
... Five hundred and fifty-two papers, including one hundred and twenty reviews and meta-analyses, were screened. Out of them, 15 were included in the final analysis according to the selected criteria [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. ...
... Consistent with this finding, Chumpitazi et al., in a randomized-controlled trial conducted on 33 children, demonstrated that a low FODMAP diet decreases IBS symptoms in children. In fact, after 2 days of low-FODMAP diet, children had fewer daily abdominal pain episodes, decreased median pain severity and lower breath hydrogen production [19]. The presumed mediator of this diet efficacy is decreased microbial fermentation, with benefits on intestinal barrier function and homeostasis. ...
Article
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Functional gastrointestinal disorders (FGIDs) are very common and life-impacting in children and young adults, covering 50% of pediatric gastroenterologist consultations. As it is known, FGIDs may be due to alterations in the gut–brain axis, dysbiosis and dysregulation of intestinal barrier, causing leaky gut. This may enhance increased antigen and bacterial passage through a damaged mucosa, worsening the impact of different medical conditions such as FGIDs. Little is known about the role of nutrients in modifying this “barrier disruption”. This narrative review aims to analyze the clinical evidence concerning diet and Intestinal Permeability (IP) in FGIDs in children. We searched the PubMed/Medline library for articles published between January 2000 and November 2021 including children aged 0–18 years old, using keywords related to the topic. Since diet induces changes in the intestinal barrier and microbiota, we aimed at clarifying how it is possible to modify IP in FGIDs by diet modulation, and how this can impact on gastrointestinal symptoms. We found that) is that small changes in eating habits, such as a low-FODMAP diet, an adequate intake of fiber and intestinal microbiota modulation by prebiotics and probiotics, seem to lead to big improvements in quality of life.
... With the increase in studies targeting the microbiota to improve human health, interindividual variability in metabolic response to these interventions is increasingly being described (e.g., [491][492][493], with some studies reporting that <30% of participants reach the desired outcome (494). Identifying which diet an individual could benefit from is an important consideration for the development of dietary therapies for certain diseases, but also for designing personalized nutrition approaches. ...
... A further example is the isoflavone metabolite equol, which has considerable estrogenic properties, but upwards of half of the population lack the microbiota composition to produce it (509). Which microbial enzymatic repertoire is required for a dietary intervention to be successful depends on the nutrients present in the study diet (70,494,510). ...
Article
Over the past decade, the gut microbiota has emerged as a key component in regulating brain processes and behavior. Diet is one of the major factors involved in shaping the gut microbiota composition across the lifespan. However, whether and how diet can affect the brain via its effects on the microbiota is only now beginning to receive attention. Several mechanisms for gut-to-brain communication have been identified, including microbial metabolites, immune, neuronal, and metabolic pathways, some of which could be prone to dietary modulation. Animal studies investigating the potential of nutritional interventions on the microbiota–gut–brain axis have led to advancements in our understanding of the role of diet in this bidirectional communication. In this review, we summarize the current state of the literature triangulating diet, microbiota, and host behavior/brain processes and discuss potential underlying mechanisms. Additionally, determinants of the responsiveness to a dietary intervention and evidence for the microbiota as an underlying modulator of the effect of diet on brain health are outlined. In particular, we emphasize the understudied use of whole-dietary approaches in this endeavor and the need for greater evidence from clinical populations. While promising results are reported, additional data, specifically from clinical cohorts, are required to provide evidence-based recommendations for the development of microbiota-targeted, whole-dietary strategies to improve brain and mental health.
... In this 6-week, controlled, dietary intervention study, a clinically signi cant improvement in IBS-SSS was observed after the dietary intervention compared to the baseline. Several other clinical trials have also shown that a low-FODMAP diet associates with an improvement in IBS symptom scores and effectively increased quality of life in patients with IBS [19,27,[31][32][33][34]. It is now well documented that IBS is a condition in which several pathophysiological mechanisms are involved in its development and symptom severity. ...
... Furthermore, data obtained from a randomized clinical trial in childhood IBS demonstrated that individuals who respond to a low-FODMAP diet have a greater capacity for saccharolytic metabolism mainly due to higher proportions of Bacteroidaceae, Erysipilotrichaceae and Clostridiales species than non-responders [33]. Rajilić-Stojanović et al. also reported an approximately 2-fold increase in the F/B ratio as the major bacterial phyla in 62 IBS patients (Rome II criteria) compared with 46 healthy subjects [43]. ...
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Background & objective: Recently, dietary restriction of fermentable carbohydrates (a low-FODMAP diet) in combination with a gluten-free diet (GFD) has been proposed to reduce the symptoms in irritable bowel syndrome (IBS) patients. Different studies reported that IBS has been associated with dysbiosis in the gut microbiota. Additionally, a few studies have reported inflammation in gastrointestinal (GI) system of adults with IBS. In this study we aim to investigate the effects of GFD and low-FODMAP diet on clinical symptoms, intestinal microbiota diversity, and fecal calprotectin (FC) level in Iranian patients with IBS. Design: In this clinical trial study, 42 patients with IBS (Rome IV criteria) underwent GFD + low-FODMAP dietary intervention for 6 weeks. Symptoms were assessed using the IBS symptom severity scoring (IBS-SSS), and fecal samples were collected at baseline and after intervention and analyzed by quantitative 16S rRNA PCR assay. The diversity of gut microbiota compared before and after 6 weeks of dietary intervention. FC was also analyzed by ELISA method. Results: Thirty patients (mean age 37.8 ± 10.7 years) completed the 6-week diet. The IBS-SSS was significantly (P = 0.038) reduced after GFD + low-FODMAP dietary intervention compared to the baseline. Significant microbial differences before and after intervention were noticed in fecal samples. A significant increase was found in Bacteroidetes, and the Firmicutes to Bacteroidetes (F/B) ratio was significantly ( P = 0.001) decreased after the dietary intervention. The value of FC was significantly decreased after 6 weeks dietary intervention (P = 0.001). Conclusions: Our study suggests that patients with IBS under a GFD + low-FODMAP diet had a significant improvement in IBS symptoms severity, with reduced FC level following normalization of their gut microbiota composition. Further rigorous trials are needed to establish long-term efficacy and safety of this dietary intervention for personalized nutrition in IBS.
... Ob diese Ursache oder Folge des RDS sind, bleibt noch unklar [794]. Möglicherweise spielen Mikrobiom-Signaturen eine Rolle beim Ansprechen auf spezifische Diäten [795]. ...
... Im Vergleich zur Normalnahrung zu Hause (1,4 ± 0,2), hatten die Kinder weniger Bauchschmerzepisoden, während die typische amerikanische Kost zu mehr Beschwerdeepisoden führte. Parallel wurden Veränderungen der Dickdarmmikrobiota bei den Respondern gefunden [795]. Aufgrund der geringen Fallzahl und der sehr kurzen Interventionsperioden und Beobachtungszeiträume reicht die Evidenz nicht zu einer Empfehlung aus. ...
... 72 A double-blind cross-over trial comparing the low FODMAP diet to the "the typical American childhood diet" found decreased abdominal pain with the low FODMAP diet. 73 Efficacy of the diet appears to be related to the baseline microbial composition. [73][74][75] Although short-term studies suggests efficacy, studies assessing whether a low FODMAP diet results in long-term benefit are needed in children. ...
... 73 Efficacy of the diet appears to be related to the baseline microbial composition. [73][74][75] Although short-term studies suggests efficacy, studies assessing whether a low FODMAP diet results in long-term benefit are needed in children. The diet places a high burden on the patient and family and has potential for adverse effects including decreased fiber and calcium intake, as well as a decrease in potentially beneficial bacteria. ...
Article
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Craig Friesen, Jennifer M Colombo, Amanda Deacy, Jennifer V Schurman Division of Gastroenterology, Hepatology, and Nutrition; Children’s Mercy Kansas City, Kansas City, MO, USACorrespondence: Craig Friesen Tel +1-816-302-3065Fax +1-816-302-9735Email cfriesen@cmh.eduAbstract: Chronic abdominal pain is very common in children and adolescent and results in high personal and social costs. Most youth with chronic abdominal pain fulfill criteria for a functional abdominal pain disorder (FAPD) as defined by Rome criteria. These are complex conditions with a wide array of biological, psychological, and social factors contributing to the experience of pain. The purpose of the current review is to provide an overview of the pathophysiology of FAPDs and an up-to-date summary of the literature related to FAPDs in children and adolescents, with additional focus on several areas (eg, diet and probiotics) where patients and families frequently have questions or implement self-directed care. We also provide an approach to the assessment and treatment of pediatric FAPDs focusing on the robust literature regarding psychological interventions and much sparser literature regarding medication treatment.Keywords: abdominal pain, functional abdominal pain disorders, functional dyspepsia, irritable bowel syndrome, biopsychosocial model
... A sample size calculation using data from a previous study in patients with IBD was performed [15]. According to this calculation a minimum difference in the symptom score on a VAS of 2.5, a standard deviation of 2.3 with 80% power and α = 0.05 a total of 45 patients, 15 in each group, were needed. ...
... Additionally, within-person standard deviations were not available at the time. The initial power calculation for this RCT study was designed for a parallel trial with symptom diary as the primary outcome using data from a previous study in patients with IBD [15]. According to this calculation, a minimum difference in the symptom score on a VAS of 2.5, a standard deviation of 2.3 with 80% power and α = 0.05, 45 patients were needed for a parallel study. ...
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Background: Patients with inflammatory bowel disease (IBD) and symptoms of irritable bowel syndrome (IBS) may be intolerant to fermentable carbohydrates (FODMAPs). The aim of this study was to test the feasibility of eliminating and subsequently reintroducing FODMAPs in patients with IBS symptoms as part of the IBD manifestation and to compare the severity of IBS symptoms and pain, bloating and quality of life (QoL). Methods: An eight-week randomised open-label FODMAP elimination with double-blinded, crossover provocations of FODMAP and placebo. Diet patients were on a low-FODMAP diet for eight weeks with blinded two-week provocations after two and six weeks. Questionnaires, blood and stool samples were collected. Results: Patient enrolment was challenging. Nineteen participants were included in the study. Eliminating low FODMAP for two weeks resulted in significant decreases in pain and bloating scores (p < 0.003), whereas there were no statistical differences in pain scores between diet patients and controls. Pain and bloating scores increased, returning to baseline levels after two weeks of double-blinded provocations with placebo, (p > 0.05). Conclusions: The results document the possibility of performing a randomised controlled study following the gold standard for testing food intolerance with blinding of the Low FODMAP diet. Recruitment of participants was challenging.
... Linear discriminant analysis effect size (LEfSe) was used to determine which OTUs had differences between the groups under different biological conditions. LEfSe is suitable for the discovery and interpretation of multilevel biological identification and characteristics, such as species taxonomy pedigrees (24). The Shannon sparse curve was drawn using the Shannon index, which is used to evaluate whether the amount of sequencing data is sufficient to cover all bacterial species and reflect the species richness in the sample (25,26). ...
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Background: To observe the effects of inhaled corticosteroids (ICS) and systemic corticosteroids (SCS) on the sputum microbiology of patients with AECOPD. Methods: The 16S rRNA sequencing results for sputum samples from 36 admitted AECOPD patients were analyzed using ICS or SCS on the basis of standard treatment; sputum samples were collected before and after treatment for 1 day, 7, and 14 days. Results: After 7 days of SCS treatment, the bacterial abundance of Sorangium, Acidibacter , and Fretibacterium decreased at the genus level. After 14 days of SCS treatment, the bacterial abundance of Prevotella_2, Bergeyella, Corynebacterium_1 , and Ruminococcaceae_UCG-014 was decreased at the genus level, and an increase in the bacterial abundance of the Clostridiales_vadinBB60_group was observed at the family level. The linear discriminant analysis effect size (LEfSe) algorithm showed that after treatment for 14 days, Sphingobacterium increased in the SCS group, and Corynebacterium_1 (genus level), Bacillales (order level), and Lactobacillales (order level) decreased in the ICS group. However, the abundance of the above bacteria in each group of samples was <1%, suggesting that the two treatments may have similar effects on bacterial abundance. Alpha diversity analysis results showed that there was no significant difference in the ACE index, Chao1 index, Shannon index, or Simpson index between the ICS group and the SCS group. Beta diversity analysis showed that there was little difference in bacterial diversity among each group. BugBase predicted that although bacteria containing mobile elements in the SCS group decreased significantly compared with those in patients using ICS after treatment for 14 days, these two treatments had similar effects on other phenotype categories assigned to the bacterial contents. Conclusions: Our results show that ICS and SCS have remarkably similar effects on the sputum microbiome of AECOPD patients.
... Although dietary intervention is well-known and relatively straightforward to implement, it is not without complications. The FODMAP diet is somewhat complex and with an absence of FODMAP information on food packaging; support from specialist dietitians is required for sufficient adherence, since clinical studies show that not every patient sees improvements to symptoms on a low FODMAP diet, patient compliance is an issue (75) . ...
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This review intends to act as an overview of Fructose Malabsorption (FM) and its role in the aetiology of diseases including, but not limited to, Irritable Bowel Syndrome (IBS) and Infantile colic and the relationship between fructose absorption and the propagation of some cancers. IBS results in a variety of symptoms including stomach pains, cramps and bloating. Patients can be categorised into two groups, depending on whether the patients’ experiences either constipation (IBS-C) or diarrhoea (IBS-D). Fructose Malabsorption has been proposed as a potential cause of IBS-D and other diseases, such as infantile colic. However, our knowledge of FM is limited by our understanding of the biochemistry related to the absorption of fructose in the small intestine and FM’s relationship with Small Intestinal Bacteria Overgrowth (SIBO). It is important to consider the dietary effects on FM and most importantly, the quantity of excess free fructose consumed. The diagnosis of FM is difficult and often requires indirect means that may result in false positives. Current treatments of FM include dietary intervention, such as low fermentable oligo-, di-, mono-saccharides and polyols (FODMAP) diets and enzymatic treatments, such as the use of xylose isomerase. More research is needed to accurate diagnose and effectively treat FM. This review is designed with the goal of providing a detailed outline of the issues regarding the causes, diagnosis and treatment of FM.
... Responders were defined as those achieving a 50% reduction in daily pain episodes on the low FODMAP diet but not the TACD. At baseline, responders compared to non-responders were enriched in the Bacteroides genus, Ruminococcaceae family, and Faecalibacterium prausnitzii species, all known for saccharolytic metabolic capacity [96]. Functional metagenomic predictions made by linking taxonomic information from the 16S rRNA gene sequences to the Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested that responders had more alpha-N-arabinosfuranosidase. ...
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Irritable bowel syndrome (IBS), with its key features of abdominal pain and disturbed bowel habit, is thought by both patients and clinicians to be strongly influenced by diet. However, the complexities of diet have made identifying specific food intolerances difficult. Eating disorders can masquerade as IBS and may need specialist treatment. While typical food allergy is readily distinguished from IBS, the mechanisms of gut-specific adverse reactions to food are only just being defined. These may include gut-specific mast cell activation as well as non-specific activation by stressors and certain foods. Visceral hypersensitivity, in some cases mediated by mast cell activation, plays a key part in making otherwise innocuous gut stimuli painful. Rapidly fermented poorly absorbed carbohydrates produce gaseous distension as well as short-chain fatty acids and lowering of colonic pH which may cause symptoms in IBS patients. Limiting intake of these in low FODMAP and related diets has proven popular and apparently successful in many patients. Existing diet, colonic microbiota and their metabolic products may be helpful in predicting who will respond. Wheat intolerance may reflect the fact that wheat is often a major source of dietary FODMAPs. It may also be either a forme fruste of coeliac disease or non-specific immune activation. Wheat exclusion can be successful in some of these patients. More research is needed to fully understand the mechanisms of food intolerances and how to best ameliorate them in a personalised medicine approach to diet in IBS.
... Pathways of carbohydrate metabolism were also enriched in responders, thus suggesting that the efficacy of a low FODMAP diet might be positively influenced by host bacteria with increased fermentation capacity. 67 The putative role of gut microbiome in IBS pathogenesis makes it an attractive target for therapeutic interventions. Nonabsorbable antibiotics (ie, rifaximin) have shown some effectiveness in adult patients with IBS-diarrhoea, 68 but in children the evidence is still unclear. ...
Article
In the human gut resides a vast community of microorganisms which perform critical functions for the maintenance of whole body homeostasis. Changes in the composition and function of this community, termed microbiome, are believed to provoke disease onset, including non-communicable diseases. In this review, we debate the current evidence on the role of the gut microbiome in the pathogenesis, outcomes and management of paediatric gut disease. We conclude that even though the gut microbiome is altered in paediatric inflammatory bowel disease, coeliac disease, intestinal failure, necrotising enterocolitis and irritable bowel syndrome, there are currently very few implications for unravelling disease pathogenesis or guiding clinical practice. In the future, the gut microbiome may aid in disease differential diagnosis and prediction of clinical outcomes, and comprise a target for therapeutic interventions.
... A Bacteroides-enriched enterotype is characteristic of a high-protein, high-saturated fat Western diet, whereas a Prevotella-enriched enterotype is characteristic of a high carbohydrate, fiber-rich Mediterranean diet [66]. Dietary modifications such as exclusive enteral formula feedings and diets with a reduction in fermentable oligo-, di-, monosaccharides, and polyols (FODMAP) have been employed to reshape the gut microbiome for the relief of symptoms associated with inflammatory bowel disease and the irritable bowel syndrome, respectively [67][68][69]. Our findings of higher bacterial richness and α-diversity among RTT individuals who consumed table foods compared with those who primarily received formula suggest a potential benefit of table foods, particularly a vegetable-rich, fiber-rich diet [70]. ...
Article
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Background Gastrointestinal problems affect the health and quality of life of individuals with Rett syndrome (RTT) and pose a medical hardship for their caregivers. We hypothesized that the variability in the RTT phenotype contributes to the dysbiosis of the gut microbiome and metabolome in RTT, predisposing these individuals to gastrointestinal dysfunction.Objectives We characterized the gut bacterial microbiome and metabolome in girls and young women with RTT (n = 44) and unaffected controls (n = 21), and examined the relation between the composition of the microbiome and variations in the RTT phenotype.Methods Demographics and clinical information, including growth and anthropometric measurements, pubertal status, symptoms, clinical severity score, bowel movement, medication use, and dietary intakes were collected from the participants. Fecal samples were collected for analysis of the gut microbiome using Illumina MiSeq-based next-generation sequencing of the 16S rRNA gene followed by bioinformatics analysis of microbial composition, diversity, and community structure. Selected end-products of microbial protein metabolism were characterized by liquid chromatography-mass spectrometry.ResultsThe gut bacterial microbiome differed within the RTT cohort based on pubertal status (p
... Thirty-three children completed the study. Children on a low-FODMAP diet had significantly fewer pain episodes compared to their baseline and to children on TACD [122]. ...
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In the last decade, the role of nutritional management in pediatric gastrointestinal diseases has gained increasing popularity. Disease-specific diets have been introduced as conventional treatments by international guidelines. Patients tend to more willingly accept food-based therapies than drugs because of their relatively “harmless” nature. Apart from a diet’s therapeutic role, nutritional support is crucial in maintaining growth and improving clinical outcomes in pediatric patients. Despite the absence of classical “side effects”, however, it should be emphasized that any dietary modification might have negative consequences on children’s growth and development. Hence, expert supervision is always advised, in order to support adequate nutritional requirements. Unfortunately, the media provide an inaccurate perception of the role of diet for gastrointestinal diseases, leading to misconceptions by patients or their caregivers that tends to overestimate the beneficial role of diets and underestimate the potential adverse effects. Moreover, not only patients, but also healthcare professionals, have a number of misconceptions about the nutritional benefits of diet modification on gastrointestinal diseases. The aim of this review is to highlight the role of diet in pediatric gastrointestinal diseases, to detect misconceptions and to give a practical guide for physicians on the basis of current scientific evidence.
... In addition, they reported a significant increase in the numbers of Bacteroidetes following a 2-week GFD compared to the low-FODMAP diet (P < 0.01). Furthermore, data obtained from a randomized clinical trial in childhood IBS demonstrated that individuals who respond to a low-FODMAP diet have a greater capacity for saccharolytic metabolism mainly due to higher proportions of Bacteroidaceae, Erysipilotrichaceae, and Clostridiales species than nonresponders [33]. Rajilić-Stojanović et al. also reported an approximately twofold increase in the F/B ratio as the major bacterial phyla in 62 IBS patients (Rome II criteria) compared with 46 healthy subjects [34]. ...
Article
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Background and objective Recently, dietary restriction of fermentable carbohydrates (a low-FODMAP diet) in combination with a gluten-free diet (GFD) has been proposed to reduce the symptoms in irritable bowel syndrome (IBS) patients. Different studies reported that IBS has been associated with dysbiosis in the gut microbiota. Additionally, a few studies have reported inflammation in the gastrointestinal (GI) system of adults with IBS. In this study, we aimed to investigate the effects of low FODMAP-gluten free diet (LF-GFD) on clinical symptoms, intestinal microbiota diversity, and fecal calprotectin (FC) level in Iranian patients with IBS. Design In this clinical trial study, 42 patients with IBS (Rome IV criteria) underwent LF-GFD intervention for 6 weeks. Symptoms were assessed using the IBS symptom severity scoring (IBS-SSS), and fecal samples were collected at baseline and after intervention and analyzed by quantitative 16 S rRNA PCR assay. The diversity of gut microbiota compared before and after 6 weeks of dietary intervention. FC was also analyzed by the ELISA method. Results Thirty patients (mean age 37.8 ± 10.7 years) completed the 6-week diet. The IBS-SSS was significantly ( P = 0.001) reduced after LF-GFD intervention compared to the baseline. Significant microbial differences before and after intervention were noticed in fecal samples. A significant increase was found in Bacteroidetes , and the Firmicutes to Bacteroidetes (F/B) ratio was significantly ( P = 0.001) decreased after the dietary intervention. The value of FC was significantly decreased after 6 weeks of dietary intervention ( P = 0.001). Conclusions Our study suggests that patients with IBS under an LF-GFD had a significant improvement in IBS symptoms severity, with reduced FC level following normalization of their gut microbiota composition. Further rigorous trials are needed to establish a long-term efficacy and safety of this dietary intervention for personalized nutrition in IBS. Clinical Trial Registry Number: IRCT20100524004010N26.
... FODMAPs are fermentable prebiotics, which are thought to increase colonic gas production, causing visceral hypersensitivity to colonic distention in IBS patients (Major et al., 2017). Interestingly, the low FODMAPs diet has also been shown to be effective for abdominal pain in IBD patients in remission (Prince et al., 2016;Cox et al., 2020), suggesting that "saccharolytic-rich dysbiosis, " may be a common microbial cause that contributes to the pathogenesis of visceral hypersensitivity in both IBD and IBS patients (Chumpitazi et al., 2015;Rossi et al., 2018). ...
Article
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Inflammatory bowel disease (IBD), comprising Crohn’s disease and Ulcerative colitis, is a relapsing and remitting disease of the gastrointestinal tract, presenting with chronic inflammation, ulceration, gastrointestinal bleeding, and abdominal pain. Up to 80% of patients suffering from IBD experience acute pain, which dissipates when the underlying inflammation and tissue damage resolves. However, despite achieving endoscopic remission with no signs of ongoing intestinal inflammation or damage, 30–50% of IBD patients in remission experience chronic abdominal pain, suggesting altered sensory neuronal processing in this disorder. Furthermore, effective treatment for chronic pain is limited such that 5–25% of IBD outpatients are treated with narcotics, with associated morbidity and mortality. IBD patients commonly present with substantial alterations to the microbial community structure within the gastrointestinal tract, known as dysbiosis. The same is also true in irritable bowel syndrome (IBS), a chronic disorder characterized by altered bowel habits and abdominal pain, in the absence of inflammation. An emerging body of literature suggests that the gut microbiome plays an important role in visceral hypersensitivity. Specific microbial metabolites have an intimate relationship with host receptors that are highly expressed on host cell and neurons, suggesting that microbial metabolites play a key role in visceral hypersensitivity. In this review, we will discuss the techniques used to analysis the metabolome, current potential metabolite targets for visceral hypersensitivity, and discuss the current literature that evaluates the role of the post-inflammatory microbiota and metabolites in visceral hypersensitivity.
... Over the last decade, research has shown that the FODMAPrestricted diet may be a safe and effective dietary intervention (56). Several studies have been conducted to conclude that an LFD is effective in relieving overall IBS symptoms and behaves either with non-inferiority or superiority with respect to other comparators (27,57,58). The consumption of an LFD has been found to improve symptoms in more than half of IBS patients (59). ...
Article
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Background There are about 10–23% of adults worldwide suffering from irritable bowel syndrome (IBS). Over the past few decades, there are many aspects of uncertainty regarding IBS leading to an ongoing interest in the topic as reflected by a vast number of publications, whose heterogeneity and variable quality may challenge researchers to measure their scientific impact, to identify collaborative networks, and to grasp actively researched themes. Accordingly, with help from bibliometric approaches, our goal is to assess the structure, evolution, and trends of IBS research between 2007 and 2022. Methods The documents exclusively focusing on IBS from 2007 to 2022 were retrieved from the Science Citation Index Expanded of the Web of Science Core Collection. The annual productivity of IBS research, and the most prolific countries or regions, authors, journals and resource-, intellectual- and knowledge-sharing in IBS research, as well as co-citation analysis of references and keywords were analyzed through Microsoft Office Excel 2019, CiteSpace, and VOSviewer. Results In total, 4,092 publications were reviewed. The USA led the list of countries with the most publications (1,226, 29.96%). Mayo Clinic contributed more publications than any other institution (193, 4.71%). MAGNUS SIMREN stood out as the most active and impactful scholar with the highest number of publications and the greatest betweenness centrality value. The most high-yield journal in this field was Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society (275, 6.72%). Gastroenterology had the most co-citations (3,721, 3.60%). Keywords with the ongoing strong citation bursts were chromogranin A, rat model, peptide YY, gut microbiota, and low-FODMAP diet, etc. Conclusion Through bibliometric analysis, we gleaned deep insight into the current status of literature investigating IBS for the first time. These findings will be useful to scholars interested in understanding the key information in the field, as well as identifying possible research frontiers.
... 9 More recently, diets avoiding fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) have demonstrated efficacy. [14][15][16][17] The mechanisms are debated, 18 but potentially involve modulation of microbiota composition and metabolite production. 19 The low FODMAP diet is challenging for many patients to follow, often requiring increased time preparing meals, recipe adaptation and fewer options for convenience foods. ...
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Objective Reducing FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) can be clinically beneficial in IBS but the mechanism is incompletely understood. We aimed to detect microbial signatures that might predict response to the low FODMAP diet and assess whether microbiota compositional and functional shifts could provide insights into its mode of action. Design We used metagenomics to determine high-resolution taxonomic and functional profiles of the stool microbiota from IBS cases and household controls (n=56 pairs) on their usual diet. Clinical response and microbiota changes were studied in 41 pairs after 4 weeks on a low FODMAP diet. Results Unsupervised analysis of baseline IBS cases pre-diet identified two distinct microbiota profiles, which we refer to as IBS P (pathogenic-like) and IBS H (health-like) subtypes. IBS P microbiomes were enriched in Firmicutes and genes for amino acid and carbohydrate metabolism, but depleted in Bacteroidetes species. IBS H microbiomes were similar to controls. On the low FODMAP diet, IBS H and control microbiota were unaffected, but the IBS P signature shifted towards a health-associated microbiome with an increase in Bacteroidetes (p=0.009), a decrease in Firmicutes species (p=0.004) and normalisation of primary metabolic genes. The clinical response to the low FODMAP diet was greater in IBS P subjects compared with IBS H (p=0.02). Conclusion 50% of IBS cases manifested a ‘pathogenic’ gut microbial signature. This shifted towards the healthy profile on the low FODMAP diet; and IBS P cases showed an enhanced clinical responsiveness to the dietary therapy. The effectiveness of FODMAP reduction in IBS P may result from the alterations in gut microbiota and metabolites produced. Microbiota signatures could be useful as biomarkers to guide IBS treatment; and investigating IBS P species and metabolic pathways might yield insights regarding IBS pathogenic mechanisms.
... This is the case of fermentable oligo-, di-and monosaccharides and polyols (FODMAPs), present in several foods from derived from plants, dairy products and sweeteners. It has been observed that when dietary FODMAP intake is reduced, symptoms such as abdominal pain, bloating, diarrhea or constipation diminish [37][38][39][40]. Thus, measuring and controlling their consumption could also make sense in CD. ...
Article
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The present work aimed to analyze, through the GlutenFreeDiet digital platform, the evolution over one year of the nutritional status, dietary profile and symptoms present among celiac people on a gluten-free diet (GFD) while receiving individualized dietary advice. Twenty-seven adults and thirty-one celiac children/adolescents participated in the study. This was then followed up by three visits, at diagnosis, and after 3 and 12 months (vt0, vt3 and vt12). Participants filled out dietary and gastrointestinal symptoms questionnaires. All patients received written personalized dietary advice from dietitians who interpreted data from the platform. Results obtained indicated that participants consumed proteins and lipids in excess and carbohydrates in defect. Low intakes of cereals, fruit and vegetables and high meat intakes were observed. However, gluten-free product (GFP) consumption and that of ultra-processed foods was reduced after 1 year in adults. Symptoms decreased after vt3 but recurred in vt12. Changes in ultra-processed foods and GFP intake, but lack of changes in the rest of the parameters suggested that the platform support was not effective enough. Even though the platform represents a useful tool for monitoring celiac patients and giving dietary advice, modules that require more continuous attention and nutritional education of patients should be provided for interventions to be more effective.
... In addition, they reported a significant increase in the numbers of Bacteroidetes following a 2-week GFD compared to the low-FODMAP diet (P < 0.01). Furthermore, data obtained from a randomized clinical trial in childhood IBS demonstrated that individuals who respond to a low-FODMAP diet have a greater capacity for saccharolytic metabolism mainly due to higher proportions of Bacteroidaceae, Erysipilotrichaceae, and Clostridiales species than nonresponders [33]. Rajilić-Stojanović et al. also reported an approximately twofold increase in the F/B ratio as the major bacterial phyla in 62 IBS patients (Rome II criteria) compared with 46 healthy subjects [34]. ...
Article
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Background and objective: Recently, dietary restriction of fermentable carbohydrates (a low-FODMAP diet) in combination with a gluten-free diet (GFD) has been proposed to reduce the symptoms in irritable bowel syndrome (IBS) patients. Different studies reported that IBS has been associated with dysbiosis in the gut microbiota. Additionally , a few studies have reported inflammation in the gastrointestinal (GI) system of adults with IBS. In this study, we aimed to investigate the effects of low FODMAP-gluten free diet (LF-GFD) on clinical symptoms, intestinal microbiota diversity, and fecal calprotectin (FC) level in Iranian patients with IBS. Design: In this clinical trial study, 42 patients with IBS (Rome IV criteria) underwent LF-GFD intervention for 6 weeks. Symptoms were assessed using the IBS symptom severity scoring (IBS-SSS), and fecal samples were collected at baseline and after intervention and analyzed by quantitative 16 S rRNA PCR assay. The diversity of gut microbiota compared before and after 6 weeks of dietary intervention. FC was also analyzed by the ELISA method. Results: Thirty patients (mean age 37.8 ± 10.7 years) completed the 6-week diet. The IBS-SSS was significantly (P = 0.001) reduced after LF-GFD intervention compared to the baseline. Significant microbial differences before and after intervention were noticed in fecal samples. A significant increase was found in Bacteroidetes, and the Firmicutes to Bacteroidetes (F/B) ratio was significantly (P = 0.001) decreased after the dietary intervention. The value of FC was significantly decreased after 6 weeks of dietary intervention (P = 0.001). Conclusions: Our study suggests that patients with IBS under an LF-GFD had a significant improvement in IBS symptoms severity, with reduced FC level following normalization of their gut microbiota composition. Further rigorous trials are needed to establish a long-term efficacy and safety of this dietary intervention for personalized nutrition in IBS.
... There are various ways in which FODMAPs may lead to GI symptoms, including bowel distension and alterations in the gut microbiome, GI endocrine cells, immune function, and/or the intestinal barrier [5]. Recently, Chumpitazi et al. demonstrated that in children with IBS, a low-FODMAP diet decreases abdominal pain frequency [6]; other studies showed the promising effects of low-FODMAP diets in reducing functional GI symptoms [7]. In contrast, emerging evidence supports the hypothesis that a Mediterranean diet (MD), which is rich in FODMAPs, may be beneficial for FGIDs [8,9]. ...
Article
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Background: The increased intake of FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyol) rich foods has been suggested as a possible trigger of functional gastrointestinal disorders (FGIDs). Despite the high FODMAP content, the Mediterranean diet (MD) appears to have beneficial effects on health. Our aim was to evaluate whether the prevalence of FGIDs in different Mediterranean countries may be influenced by FODMAP consumption and adherence to the MD. Methods: A school-based, cross-sectional, multicenter study was performed in six countries in the Mediterranean area: Croatia, Greece, Israel, Italy, Macedonia, and Serbia. Subjects 4-18 years were examined in relation to their eating habits and the presence of FGIDs, using Rome IV criteria, 3-day food diaries and Mediterranean Diet Quality Index in Children and Adolescents (KIDMED) questionnaires. Results: We enrolled 1972 subjects between 4 and 9 years old (Group A), and 2450 subjects between 10 and 18 years old (Group B). The overall prevalence of FGIDs was 16% in Group A and 26% in Group B. FODMAP intake was significantly different among countries for both age groups. In both groups, no significant association was found between FGIDs and FODMAPs. Adherence to the MD in all countries was intermediate, except for Serbia, where it was low. In both groups, we found a statistically significant association between FGIDs and the KIDMED score (Group A: OR = 0.83, p < 0.001; Group B: OR = 0.93, p = 0.005). Moreover, a significant association was found between the KIDMED score and functional constipation (Group A: OR = 0.89, p = 0.008; Group B: OR = 0.93, p = 0.010) and postprandial distress syndrome (Group A: OR = 0.86, p = 0.027; Group B: OR = 0.88, p = 0.004). Conclusions: Our data suggest that the prevalence of FGIDs in the Mediterranean area is not related to FODMAP consumption, whereas adherence to the MD seems to have a protective effect.
... If a low FODMAP diet does adversely affects the gut microbiota profile in IBS and is associated with worsening IBS, we need to determine a way to deal with these adverse effects, such as supplementation with probiotics or modulation of ingredient composition of the low FODMAP diet. In an interesting study using metagenomic sequencing in children with IBS [95]; at the baseline non-responders were enriched with the genus Turicibacter from the family Turicibacteraceae. This suggests that the profile of microbiome before starting a low FODMAP diet can be useful to predict responders and non-responders. ...
Article
Irritable bowel syndrome (IBS) is a frequently diagnosed gastrointestinal (GI) disorder characterized by recurrent abdominal pain, bloating, and changes in the stool form or frequency without any structural changes and overt inflammation. It is not a life-threatening condition but causes a considerable level of discomfort and distress. Among the many pathophysiologic factors, such as altered GI motility, visceral hypersensitivity, and low-grade mucosal inflammation, as well as other immunologic, psychologic, and genetic factors, gut microbiota imbalance (dysbiosis), which is frequently found in IBS, has been highlighted as an etiology of IBS. Dysbiosis may affect gut mucosal homeostasis, immune function, metabolic regulation, and even visceral motor function. As diet is shown to play a fundamental role in the gut microbiota profile, this review discusses the influence of diet on IBS occurring through the modulation of gut microbiota. Based on previous studies, it appears that dietary modulation of the gut microbiota may be effective for the alleviation of IBS symptoms and, also an effective IBS management strategy based on the underlying mechanism; especially because, IBS currently has no specific treatment owing to its uncertain etiology.
Article
Purpose of review: Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder (FGID) characterized by chronic abdominal pain and altered bowel habits. The diagnosis of IBS is based on the presence of defined clinical Rome IV criteria in the absence of alarm features. The majority of patients with IBS report of food triggers eliciting typical IBS symptoms and trying to modify their dietary intake. Recent findings: FGID including IBS are defined as disorders of the gut-brain interaction. A large proportion of individuals with IBS link their symptoms to dietary factors, and recent clinical studies have shown benefits of a diet low in FODMAPs (Fermentable Oligo-, Di-, and Monosaccharides and Polyols) on IBS symptoms and quality of life. Dietary interventions mediate directly changes of luminal gut contents affecting chemosensing-enteroendocrine cells in the modulation of the gut brain microbiome axis in IBS patients. Long-term assessment of clinical outcomes in patients on a low FODMAP diet is needed. Professional guidelines have incorporated the suggestion to offer IBS patients a diet low in FODMAPs. Summary: The FGIDs, including IBS, are defined as gut-brain disorders. Low FODMAP diet has been shown in clinical trials to reduce IBS symptoms but long-term efficacy and nutritional side-effects remain uncertain.
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LINKED CONTENT This article is linked to Chumpitazi et al and Halmos papers. To view these articles, visit https://doi.org/10.1111/apt.16204 and https://doi.org/10.1111/apt.16229
Article
Background and Aim Diet is a powerful tool in the management of gastrointestinal disorders, but developing diet therapies is fraught with challenge. This review discusses key lessons from the FODMAP diet journey. Methods Published literature and clinical experience were reviewed. Results Key to designing a varied, nutritionally adequate low FODMAP diet was our accurate and comprehensive database of FODMAP composition, made universally accessible via our user-friendly, digital application. Our discovery that FODMAPs coexist with gluten in cereal products, and subsequent gluten/fructan challenge studies in non-celiac gluten sensitive populations highlighted issues of collinearity in the nutrient composition of food and confirmation bias in the interpretation of dietary studies. Despite numerous challenges in designing, funding and executing dietary randomised controlled trials, efficacy of the low FODMAP diet has been repeatedly demonstrated, and confirmed by real-world experience, giving this therapy credibility in the eyes of clinicians and researchers. Furthermore, real-world application of this diet saw the evolution of a safe and effective three-phased approach. Specialist dietitians must deliver this diet to optimise outcomes as they can target and tailor the therapy, and mitigate the key risks of compromising nutritional adequacy and precipitating disordered eating behaviours, skills outside the gastroenterologist’s standard tool kit. While concurrent probiotics are ineffective, specific fiber supplements may improve short- and long-term outcomes. Conclusions The FODMAP diet is highly effective, but optimal outcomes are contingent on the involvement of a gastroenterological dietitian who can assess, educate and monitor patients and manage risks associated with implementation of this restrictive diet.
Article
Background and Purpose Changes in diet and lifestyle factors are frequently recommended for persons with irritable bowel syndrome (IBS). It is unknown whether these recommendations alter the gut microbiome and/or whether baseline microbiome predicts improvement in symptoms and quality of life following treatment. Therefore, the purpose of this study was to explore if baseline gut microbiome composition predicted response to a Comprehensive Self-Management (CSM) intervention and if the intervention resulted in a different gut microbiome composition compared to usual care. Methods Individuals aged 18–70 years with IBS symptoms ≥6 months were recruited using convenience sampling. Individuals were excluded if medication use or comorbidities would influence symptoms or microbiome. Participants completed a baseline assessment and were randomized into the eight-session CSM intervention which included dietary education and cognitive behavioral therapy versus usual care. Questionnaires included demographics, quality of life, and symptom diaries. Fecal samples were collected at baseline and 3-month post-randomization for 16S rRNA-based microbiome analysis. Results Within the CSM intervention group (n = 30), Shannon diversity, richness, and beta diversity measures at baseline did not predict benefit from the CSM intervention at 3 months, as measured by change in abdominal pain and quality of life. Based on both alpha and beta diversity, the change from baseline to follow-up microbiome bacterial taxa did not differ between CSM (n = 25) and usual care (n = 25). Conclusions and Inferences Baseline microbiome does not predict symptom improvement with CSM intervention. We do not find evidence that the CSM intervention influences gut microbiome diversity or composition over the course of 3 months.
Article
Objective Identification of microbiota-based biomarkers as predictors of low-FODMAP diet response and design of a diet recommendation strategy for IBS patients. Design We created a compendium of gut microbiome and disease severity data before and after a low-FODMAP diet treatment from published studies followed by unified data processing, statistical analysis and predictive modeling. We employed data-driven methods that solely rely on the compendium data, as well as hypothesis-driven methods that focus on methane and short chain fatty acid (SCFA) metabolism pathways that were implicated in the disease etiology. Results The patient’s response to a low-FODMAP diet was predictable using their pre-diet fecal samples with F1 accuracy scores of 0.750 and 0.875 achieved through data-driven and hypothesis-driven predictors, respectively. The fecal microbiome of patients with high response had higher abundance of methane and SCFA metabolism pathways compared to patients with no response (p-values < 6×10⁻³). The genera Ruminococcus 1, Ruminococcaceae UCG-002 and Anaerostipes can be used as predictive biomarkers of diet response. Furthermore, the low-FODMAP diet followers were identifiable given their microbiome data (F1-score of 0.656). Conclusion Our integrated data analysis results argue that there are two types of patients, those with high colonic methane and SCFA production, who will respond well on a low-FODMAP diet, and all others, who would benefit a dietary supplementation containing butyrate and propionate, as well as probiotics with SCFA-producing bacteria, such as lactobacillus. This work demonstrates how data integration can lead to novel discoveries and paves the way towards personalized diet recommendations for IBS.
Article
An innovative investigation was undertaken into the abundance and diversity of high antibiotic-resistant bacteria in aquaculture waters in Shandong Province, China, through cumulation incubation, PCR amplification of 16S rDNA, and high-throughput sequencing. The results showed that Vibrio, Bacillus, Vagococcus, Acinetobacter, Shewanella, Psychrobacter, Lactococcus, Enterococcus, Marinimonus and Myroids were abundant in the aquaculture waters, whereas other phylum including Actinobacteria, Deinococcus-Thermus, Omnitrophica and Nitrospirae had relatively lower abundance. Our studies revealed the presence of different bacteria in different locations in the aquaculture waters, most of which were resistant to multiple antibiotics. That is, the same microbial species from the same aquaculture wastewater can resist different antibiotics. Altogether, a considerable portion of the microbial community were found to be multi-drug resistant. It is essential that the spread of the antibiotic-resistant bacteria is controlled so that the distribution of antibiotic resistance genes to other environments is avoided. Supplementary information: The online version contains supplementary material available at 10.1007/s13205-021-02656-4.
Chapter
The gut microbiota is now well recognized as a key component in regulating various human processes, including metabolism, cardiovascular system, immunity, as well as brain and cognitive function. Diet has emerged as a main contributor to the microbiota composition and functional capacity; as such, increasing research is also now deciphering the food-microbiota interaction as a modulator of health and disease. Here, we review this food-microbiota interaction from a viewpoint of nutrient bioavailability and the importance in host health (including obesity, metabolic health, immunity, gastrointestinal, and mental health). Additionally, underlying mechanisms (e.g., gut hormones, microbial metabolites, epigenetic modulation, or inflammation) will be discussed in the context of different host outcomes. Furthering the understanding of the diet-gut microbes interaction and its significance for the host will be imperative in the development of future microbiota-targeted dietary approaches to improve health.
Article
Chronic recurrent abdominal pain in school-aged children mostly has no detectable organic cause and functional disorders should be diagnosed. The spectrum of possible organic causes is broad and rare diseases must also be considered; however, overdiagnostics should be avoided. Anamnesis, complete physical examination and focused basic diagnostics narrow down the organic diagnoses and the necessity for further diagnostics is checked. With negative basic diagnostics and no red flags, no further investigations are necessary. The clear diagnosis of a functional disorder (positive connotation) is the basis for successful treatment using cognitive-behavioral therapy methods. In most cases drug treatment does not play a role in functional disorders. Dietary interventions should only be recommended in cases of a clearly demonstrated intolerance. The aim for the patient is to learn how to cope with and forget the pain and the aim for the physician is to identify patients with lasting impairments.
Chapter
Functional gastrointestinal disorders (FGIDs) compose more than half of new pediatric gastroenterology clinic visits and can lead to functional disability, impaired quality of life, and a cost burden on healthcare. They can be associated with motility disturbances, visceral hypersensitivity, altered mucosal and immune function, gut microbiota, and central nervous system processing; however, general evidence of tissue damage is lacking. To fully understand the pathophysiology of FGIDs, it is important to comprehend the biopsychosocial model, which differs from the biomedical model. It focuses on understanding and treating illness and the patient’s subjective sense of suffering, rather than confining the diagnostic effort to finding disease. Medical tests are not necessary to make a diagnosis of an FGID. The Rome diagnostic criteria, developed through evidence-based research and clinical consensus, provide symptom-based diagnoses for neonatal, toddler, child, and adolescent FGIDs. The clinical interview of children or adolescents with FGID relies heavily on education, effective reassurance, and an individualized treatment plan tailoring to the patient and their family. This chapter highlights conceptual groundwork and concrete suggestions for recognizing and managing patients with FGIDs.
Chapter
Chronic abdominal pain is common in children and in the majority of cases is functional in nature. For children with abdominal pain lasting 2 months or longer, the Rome IV criteria should be used to diagnose a functional abdominal pain disorder (FAPD). Recent advances have furthered our understanding of the pathogenesis, evaluation, and management of pediatric FAPDs, but these disorders remain challenging to recognize and treat successfully. Effective management requires an understanding of the many factors that can contribute to an individual child’s presentation. Treatment of an FAPD should be tailored to the individual and can include a combination of pharmacologic, dietary, and psychosocial interventions.
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Disorders of the gut-brain interaction negatively impact quality of life and carry a substantial socioeconomic burden. Irritable bowel syndrome (IBS) and functional abdominal pain-not otherwise specified (FAP-NOS) are common functional abdominal pain disorders in childhood. The pathophysiology is not fully understood, and high-quality intervention trials and international guidelines are missing. Therefore, the management of these disorders remains challenging. This review aims to provide an up-to-date overview of therapeutic possibilities for pediatric IBS or FAP-NOS and recommends management strategies. To prevent unnecessary referrals and extensive costs, it is fundamental to make a positive diagnosis of IBS or FAP-NOS in children with chronic abdominal pain with only minimal investigations. A tailor-made approach for each patient, based on the accompanying physical and psychological symptoms, is proposed to date. Conclusion : Shared decision-making including non-pharmacological and pharmacological interventions should be considered and discussed with the family. What is Known: • Irritable bowel syndrome and functional abdominal pain-not otherwise specified are common in childhood. • Although the number of treatment options has grown recently, managing these disorders can be challenging and unsatisfactory, and no evidence-based international management guidelines are available. What is New: • We suggest using a stepwise individualized approach to management, where after first-line management, both non-pharmacological and pharmacological interventions should be discussed.
Article
Background: IBS affects a large number of children throughout the world and is thought to be the result of disturbed neuroimmune function along with the brain-gut axis. Although the underlying pathophysiologic mechanisms are not clear, the role of low-grade inflammation and mucosal immune activation in IBS symptom generation has become evident also in subsets of pediatric patients. Animal models provided meaningful insight in the causal relationship between abnormal mucosal immune activation and changes in gastrointestinal (GI) sensory-motor function. Likewise, the development of long-standing GI symptoms fulfilling the current criteria for functional GI disorders after infection gastroenteritis and in patients with IBD or celiac disease in remission further supports this hypothesis. Immune activation, its impact on gut sensory-motor function, and potential implications for symptom generation emerged in both children and adults with IBS. Purpose: The aim of this review is to summarize the main evidence on the presence of low-grade inflammation and immune activation in children with IBS, its possible role in symptom generation, and its potential implication for new therapeutic strategies.
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Background Short-chain fatty acids (SCFAs) derived from gut bacteria are associated with protective roles in diseases ranging from obesity to colorectal cancers. Intake of microbially accessible dietary fibers (prebiotics) lead to varying effects on SCFA production in human studies, and gut microbial responses to nutritional interventions vary by individual. It is therefore possible that prebiotic therapies will require customizing to individuals. Results Here, we explored prebiotic personalization by conducting a three-way crossover study of three prebiotic treatments in healthy adults. We found that within individuals, metabolic responses were correlated across the three prebiotics. Individual identity, rather than prebiotic choice, was also the major determinant of SCFA response. Across individuals, prebiotic response was inversely related to basal fecal SCFA concentration, which, in turn, was associated with habitual fiber intake. Experimental measures of gut microbial SCFA production for each participant also negatively correlated with fiber consumption, supporting a model in which individuals’ gut microbiota are limited in their overall capacity to produce fecal SCFAs from fiber. Conclusions Our findings support developing personalized prebiotic regimens that focus on selecting individuals who stand to benefit, and that such individuals are likely to be deficient in fiber intake.
Article
Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain and altered bowel habit. IBS patients report that FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols) diet induce or exacerbate their symptoms. It has been reported that low-FODMAP diet (LFD) improves the symptoms in 50%-80% of IBS patients. We aimed to identify IBS responders and non-responders' patients to LFD by determining baseline fecal microbial composition, sequencing the 16S rRNA gene V3-V4 region. Thirty-two participants with IBS were included, 29 women (90.62%) and three men (9.37%), and instructed to follow a four-week LFD, Visual Analogue Scale for IBS was used to assess intervention response. Twenty-two participants were responders (68.75%), and ten were non-responders (31.25%). Differential abundance analysis of Amplicon Sequence Variant (ASVs), before LFD, identified Prevotella 9 and Veillonella genus in responder group, and Barnesiella, Paraprevotella, Bifidobacterium and Ruminococcus 1 genus in non-responder group. After LFD, differentially abundant ASVs were only identified in R, belonging to Veilonella, Butyrivibrio, and 5 ASVs belonging to Ruminiclostridium 6 genus. Linear Discriminant Analysis (LDA), was used to classify patients by responsiveness, considering baseline abundance of 5 bacterial genera, LDA accuracy model was 96.87%, correctly classifying 95.45% of in responder group and 100% and non-responder group. In conclusion, bacterial biomarkers are useful to classify IBS individuals by responsiveness to LFD.
Article
Objectives: To characterize the types of multisite pain experienced by children with functional abdominal pain disorders (FAPDs) and to examine differences in psychosocial distress, functional disability and health-related quality of life in children with multisite pain vs. abdominal pain alone. Study design: Cross-sectional study of children ages 7-17 years (n=406) with pediatric Rome III FAPDs recruited from both primary and tertiary care between January 2009 and June 2018. Subjects completed 14-day pain and stool diaries, as well as validated questionnaires assessing abdominal and non-abdominal pain symptoms, anxiety, depression, functional disability and health-related quality of life. Results: 295 (73%) children endorsed at least one co-occurring non-abdominal pain thus were categorized as having multisite pain with the following symptoms: 172 (42%) headaches, 143 (35%) chest pain, 134 (33%) muscle soreness, 110 (27%) back pain, 94 (23%) joint pain, and 87 (21%) extremity (arms and legs) pain. In addition, 200 children (49%) endorsed two or more non-abdominal pain symptoms. Participants with (vs without) multisite pain had significantly higher abdominal pain frequency (P<0.001) and severity (P = .03), anxiety (P<0.001), and depression (P<0.001). Similarly, children with multisite pain (vs. without) had significantly worse functional disability (P<0.001) and health-related quality of life scores (P<0.001). Increasing number of multisite pain sites (P<0.001) was associated with increased functional disability when controlling for demographic and other clinical factors. Conclusions: In children with FAPDs, non-abdominal multisite pain is highly prevalent and is associated with increased psychosocial distress, abdominal pain frequency and severity, functional disability, and lower health-related quality of life.
Article
Irritable bowel syndrome (IBS) patients often resort to dietary interventions to manage their symptoms, as these are frequently exacerbated by various food items. A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) is now considered by many a first-line treatment option for IBS, as it has been found to be superior to alternative dietary interventions. However, concerns have been raised as restricting fermentable carbohydrates might result in nutritional deficits or alter composition and function of the gut microbiome in the long term. The study by Staudacher et al., published in this issue of the journal, is the first prospective study to follow IBS patients after completing all three phases of the low FODMAPs diet (restriction, reintroduction, and personalization), demonstrating that this is safe and effective in long-term, when patients are supervised by a dietician. This mini-review provides an up-to-date overview of the use of fermentable carbohydrate's restrictions for symptom management in IBS patients, while summarizing the current knowledge on the possible mechanisms of action behind low fermentable carbohydrate diet efficacy.
Article
Intake of fermentable Oligo,- Di,- Monosaccharides, And Polyols, abbreviated as FODMAP, is known to worsen gastrointestinal symptoms in people with functional bowel disorders. Legume-based foods are climate-friendly and healthy alternatives to meat, but also high in fermentable oligosaccharides, galactooligosaccharides in particular. In this study, we have screened commercial and produced new α-galactosidases for hydrolysis of galactooligosaccharides in pea and faba bean based materials. Commercial DS30 and recombinantly produced Neosartorya fisherii α-galactosidase were further applied to enzymatic removal of galactooligosaccharides from leguminous ingredients as well as moist (spoonable), semi-moist (wet-extrudate) and dry (crackers) food prototypes. Galactooligosaccharide levels were reduced by both enzymes by over 90% during production of a pea protein-based spoonable product and formulations prepared for extrusion cooking. Extrusion cooking increased the analyzable galactooligosaccharide content to some extent, presumably because heating and shearing released more galactooligosaccharides from the material. Cracker dough galactooligosaccharide concentration was decreased less during α-galactosidase treatment, most likely because slightly alkaline pH of the material, which was not optimal for α-galactosidase action.
Article
Diet is increasingly appreciated to have a tremendous impact on many aspects of the host’s biology in health and disease. Dietary content and timing are also central in shaping the gut microbiome, and contribute to its taxonomic and functional diversity. Regardless, current dietary recommendations remain largely non-personalized, and feature disappointing long-term efficacy in treating obesity and its complications. Personalized nutrition aims to utilize inter-individual host and microbiome variations in generating data-driven personalized dietary recommendations. While personalized nutrition has yielded encouraging and potentially clinically applicable results across several cohorts, host-microbiome interaction networks driving such crosstalk and the mechanisms mediating their metabolic impact remain elusive and merit further studies. Herein, we summarize the latest advances in utilizing diet-microbiota interactions towards the development of personalized nutrition, while focusing on the prospects, challenges and unknowns in integrating this promising new data-driven approach into human precision health.
Article
Background and Aim Previous studies have shown a reduction of gastrointestinal symptoms in irritable bowel syndrome (IBS) patients following a low FODMAP diet (LFD). It remains unknown, which disorders of gut-brain interaction (DGBI) patients, would benefit most from LFD. We aimed to analyze LFD response regarding a preceding nutrient challenge test (NCT). Methods Data of 110 consecutive DGBI patients undergoing NCT and LFD between 08/2015-2018 were analyzed retrospectively. LFD response was assessed by changes in IBS – Symptom Severity Score (IBS-SSS). In mixed-effects linear regression models the impact of hydrogen values and abdominal symptoms during NCT, performed with 30g lactulose and 400ml liquid test meal, on IBS-SSS changes were analyzed. Results LFD induced a significant IBS-SSS reduction of 78 points (95% CI: 50-96; p < 0.001). Patients with higher NCT-induced hydrogen increase during proximal intestinal transit had a significantly better LFD response (-66 IBS-SSS reduction per 10 ppm hydrogen increase, 95% CI -129 - -4, p = 0.045). Additionally, the higher the NCT-induced maximum hydrogen increase during mid- and distal intestinal transit the better the responses to LFD (-6 IBS-SSS per 10ppm maximum delta hydrogen, 95% CI -11 - -1, p=0.040). There was no association of LFD response with abdominal symptom generation during NCT. Conclusions Our study is the first one analyzing and demonstrating significant associations between NCT results and LFD response. These findings are of high clinical importance, as they identify a subgroup of DGBI patients that may profit most from a restrictive LFD as first-line therapy.
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Background: Probiotic and low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet are two commonly used management approaches for patients with irritable bowel syndrome (IBS). We aimed to evaluate the most effective combinations and components among different probiotics or low FODMAP diet through component network meta-analysis (NMA). Methods: We searched Embase, Ovid Medline, and Web of Science from inception to 21 January 2021. Randomized controlled trials (RCTs) examining the efficacy of probiotics and low FODMAP diet for IBS were included, with placebo, sham diet, or conventional treatments as controls. Binary outcomes were compared among treatments using the relative ratio (RR). A minimally contextualized framework recommended by the GRADE group was used to evaluate the certainty of evidence. The primary efficacy outcome was the relief of global IBS symptoms, and the secondary efficacy outcome was the reduction in IBS symptom scores or abdominal pain scores. Key Results: We included 76 RCTs (n = 8058) after screening 1940 articles. Eight RCTs were classified as low risk of bias. Standard network meta-analysis (NMA) showed that Lactobacillus (RR 1.74, 95% CI 1.22–2.48) and Bifidobacterium (RR 1.76, 95% CI 1.01–3.07) were the most effective for the primary efficacy outcome (high certainty evidence); component NMA showed that Bacillus (RR 5.67, 95% CI 1.88 to 17.08, p = 0.002) and Lactobacillus (RR 1.42, 95% CI 1.07 to 1.91, p = 0.017) were among the most effective components. The results of standard NMA and CNMA analysis of the improvement of overall IBS symptom scores or abdominal pain scores were consistent with this finding. Conclusion: Lactobacillus was the most effective component for the relief of IBS symptoms; Bifidobacterium and Bacillus were possibly effective and need further verification. Systematic Review Registration: website, identifier registration number.
Article
Patients with irritable bowel syndrome (IBS) frequently perceive eating food as a trigger to their gastrointestinal (GI) distress. Several factors involved in driving GI symptoms include malabsorption and fermentation of food substrates, gut microbiota alterations, nocebo and placebo response, and mast cell activation. Nutritional interventions require individualization based on the heterogeneity of symptoms as well as the risk for maladaptive eating patterns that present in those with IBS. Despite the variety of interventions marketed to individuals with IBS, the low Fermentable, Oligo-, Di-Mono-saccharide, and Polyol diet has the most evidence for efficacy in symptom management.
Article
Description Irritable bowel syndrome (IBS) is a commonly diagnosed gastrointestinal disorder that can have a substantial impact on quality of life. Most patients with IBS associate their gastrointestinal symptoms with eating food. Mounting evidence supports dietary modifications, such as the low–fermentable oligo-, di-, and monosaccharides and polyols (FODMAP) diet, as a primary treatment for IBS symptoms. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update (CPU) is to provide best practice advice statements, primarily to clinical gastroenterologists, covering the role of diet in IBS treatment. Methods This expert review was commissioned and approved by the AGA CPU Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Gastroenterology. The best practice advice statements were drawn from reviewing existing literature combined with expert opinion to provide practical advice on the role of diet in treating patients with IBS. Because this was not a systematic review, formal rating of the quality of evidence or strength of the presented considerations was not performed. Best Practice Advice Statements Best Practice Advice 1 Dietary advice is ideally prescribed to patients with IBS who have insight into their meal-related gastrointestinal symptoms and are motivated to make the necessary changes. To optimize the quality of teaching and clinical response, referral to a registered dietitian nutritionist (RDN) should be made to patients who are willing to collaborate with a RDN and patients who are not able to implement beneficial dietary changes on their own. If a gastrointestinal RDN is not available, other resources can assist with implementation of diet interventions. Best Practice Advice 2 Patients with IBS who are poor candidates for restrictive diet interventions include those consuming few culprit foods, those at risk for malnutrition, those who are food insecure, and those with an eating disorder or uncontrolled psychiatric disorder. Routine screening for disordered eating or eating disorders by careful dietary history is critical because they are common and often overlooked in gastrointestinal conditions. Best Practice Advice 3 Specific diet interventions should be attempted for a predetermined length of time. If there is no clinical response, the diet intervention should be abandoned for another treatment alternative, for example, a different diet, medication, or other form of therapy. Best Practice Advice 4 In preparation for a visit with a RDN, patients should provide dietary information that will assist in developing an individualized nutrition care plan. Best Practice Advice 5 Soluble fiber is efficacious in treating global symptoms of IBS. Best Practice Advice 6 The low-FODMAP diet is currently the most evidence-based diet intervention for IBS. Healthy eating advice as described by the National Institute of Health and Care Excellence Guidelines, among others, also offers benefit to a subset of patients with IBS. Best Practice Advice 7 The low-FODMAP diet consists of the following 3 phases: 1) restriction (lasting no more than 4–6 weeks), 2) reintroduction of FODMAP foods, and 3) personalization based on results from reintroduction. Best Practice Advice 8 Although observational studies found that most patients with IBS improve with a gluten-free diet, randomized controlled trials have yielded mixed results. Best Practice Advice 9 There are limited data showing that selected biomarkers can predict response to diet interventions in patients with IBS, but there is insufficient evidence to support their routine use in clinical practice.
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Irritable bowel syndrome (IBS) is a heterogeneous functional disorder with a multifactorial etiology that involves the interplay of both host and environmental factors. Among environmental factors relevant for IBS etiology, the diet stands out given that the majority of IBS patients report their symptoms to be triggered by meals or specific foods. The diet provides substrates for microbial fermentation, and since the composition of the intestinal microbiota is disturbed in IBS patients, the link between diet, microbiota composition and microbial fermentation products might play an essential role in IBS etiology. In this review, we summarize current evidence regarding the impact of diet and the intestinal microbiota on IBS symptoms as well as the reported interactions between diet and the microbiota composition. Based on the existing data we suggest pathways (mechanisms) by which diet components, via the microbial fermentation could trigger IBS symptoms. Finally, this review provides recommendations for future studies that would enable elucidation of the role of diet and microbiota and how these factors may be (inter)related in the pathophysiology of IBS.
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Human microbiome research is an actively developing area of inquiry, with ramifications for our lifestyles, our interactions with microbes, and how we treat disease. Advances depend on carefully executed, controlled, and reproducible studies. Here, we provide a Primer for researchers from diverse disciplines interested in conducting microbiome research. We discuss factors to be considered in the design, execution, and data analysis of microbiome studies. These recommendations should help researchers to enter and contribute to this rapidly developing field.
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Objective A low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) diet reduces symptoms of IBS, but reduction of potential prebiotic and fermentative effects might adversely affect the colonic microenvironment. The effects of a low FODMAP diet with a typical Australian diet on biomarkers of colonic health were compared in a single-blinded, randomised, cross-over trial. Design Twenty-seven IBS and six healthy subjects were randomly allocated one of two 21-day provided diets, differing only in FODMAP content (mean (95% CI) low 3.05 (1.86 to 4.25) g/day vs Australian 23.7 (16.9 to 30.6) g/day), and then crossed over to the other diet with ≥21-day washout period. Faeces passed over a 5-day run-in on their habitual diet and from day 17 to day 21 of the interventional diets were pooled, and pH, short-chain fatty acid concentrations and bacterial abundance and diversity were assessed. Results Faecal indices were similar in IBS and healthy subjects during habitual diets. The low FODMAP diet was associated with higher faecal pH (7.37 (7.23 to 7.51) vs 7.16 (7.02 to 7.30); p=0.001), similar short-chain fatty acid concentrations, greater microbial diversity and reduced total bacterial abundance (9.63 (9.53 to 9.73) vs 9.83 (9.72 to 9.93) log10 copies/g; p<0.001) compared with the Australian diet. To indicate direction of change, in comparison with the habitual diet the low FODMAP diet reduced total bacterial abundance and the typical Australian diet increased relative abundance for butyrate-producing Clostridium cluster XIVa (median ratio 6.62; p<0.001) and mucus-associated Akkermansia muciniphila (19.3; p<0.001), and reduced Ruminococcus torques. Conclusions Diets differing in FODMAP content have marked effects on gut microbiota composition. The implications of long-term reduction of intake of FODMAPs require elucidation. Trial registration number ACTRN12612001185853.
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DNA-binding transcription factors (TFs) are essential components of transcriptional regulatory networks in Bacteria. LacI-family TFs (LacI-TFs) are broadly distributed among certain lineages of bacteria. The majority of characterized LacI-TFs sense sugar effectors and regulate carbohydrate utilization genes. The comparative genomics approaches enable in silico identification of TF-binding sites and regulon reconstruction. To study function and evolution of LacI-TFs, we performed genomics-based reconstruction and comparative analysis of their regulons. For over 1,300 LacI-TFs from over 270 bacterial genomes, we predicted their cognate DNA-binding motifs and identified target genes. Using the genome context and metabolic subsystem analyses of reconstructed regulons we tentatively assigned functional roles and predicted candidate effectors for 78% and 67% of the analyzed LacI-TFs, respectively. Nearly 90% of the studied LacI-TFs are local regulators of sugar utilization pathways, whereas the remaining 125 global regulators control large and diverse sets of metabolic genes. The global LacI-TFs include the previously known regulators CcpA in Firmicutes, FruR in Enterobacteria, and PurR in Gammaproteobacteria, and the three novel regulators, GluR, GapR, and PckR, that are predicted to control the central carbohydrate metabolism in three lineages of Alphaproteobacteria. Phylogenetic analysis of regulators combined with the reconstructed regulons provides a model of evolutionary diversification of LacI-TFs. The obtained genomic collection of in silico reconstructed regulons in Bacteria is available in the RegPrecise database (http://regprecise.lbl.gov). It provides a framework for future structural and functional classification of the LacI protein family and identification of molecular determinants of the DNA and ligand specificity. The inferred regulons can be also used for functional gene annotation and reconstruction of sugar catabolic networks in diverse bacteria.
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The intestinal microbiome is a unique ecosystem and an essential mediator of metabolism and obesity in mammals. However, studies investigating the impact of the diet on the establishment of the gut microbiome early in life are generally lacking, and most notably so in primate models. Here we report that a high-fat maternal or postnatal diet, but not obesity per se, structures the offspring's intestinal microbiome in Macaca fuscata (Japanese macaque). The resultant microbial dysbiosis is only partially corrected by a low-fat, control diet after weaning. Unexpectedly, early exposure to a high-fat diet diminished the abundance of non-pathogenic Campylobacter in the juvenile gut, suggesting a potential role for dietary fat in shaping commensal microbial communities in primates. Our data challenge the concept of an obesity-causing gut microbiome and rather provide evidence for a contribution of the maternal diet in establishing the microbiota, which in turn affects intestinal maintenance of metabolic health.
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The gut microbiota is involved in metabolic and immune disorders associated with obesity and type 2 diabetes. We previously demonstrated that prebiotic treatment may significantly improve host health by modulating bacterial species related to the improvement of gut endocrine, barrier and immune functions. An analysis of the gut metagenome is needed to determine which bacterial functions and taxa are responsible for beneficial microbiota-host interactions upon nutritional intervention. We subjected mice to prebiotic (Pre) treatment under physiological (control diet: CT) and pathological conditions (high-fat diet: HFD) for 8 weeks and investigated the production of intestinal antimicrobial peptides and the gut microbiome. HFD feeding significantly decreased the expression of regenerating islet-derived 3-gamma (Reg3g) and phospholipase A2 group-II (PLA2g2) in the jejunum. Prebiotic treatment increased Reg3g expression (by ∼50-fold) and improved intestinal homeostasis as suggested by the increase in the expression of intectin, a key protein involved in intestinal epithelial cell turnover. Deep metagenomic sequencing analysis revealed that HFD and prebiotic treatment significantly affected the gut microbiome at different taxonomic levels. Functional analyses based on the occurrence of clusters of orthologous groups (COGs) of proteins also revealed distinct profiles for the HFD, Pre, HFD-Pre and CT groups. Finally, the gut microbiota modulations induced by prebiotics counteracted HFD-induced inflammation and related metabolic disorders. Thus, we identified novel putative taxa and metabolic functions that may contribute to the development of or protection against the metabolic alterations observed during HFD feeding and HFD-Pre feeding.
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Background & Aims Pharmacologic treatments for IBS and medical management of symptoms are increasingly based on IBS subtype, so it is important to accurately differentiate patients. Few studies have classified subtypes of pediatric IBS, and conclusions have been challenged by methodologic limitations. We performed a prospective study to investigate the distribution of IBS subtypes among children and adolescents based on stool diary information, and compared subtypes according to demographic and pain characteristics. Methods We studied 129 subjects, 7–18 y old (mean 11.4 ± 2.8 y old, 60.5% female, 69.0% Caucasian) who met Pediatric Rome III IBS criteria and were part of larger studies of children with functional gastrointestinal disorders, recruited from primary and tertiary care centers. Children completed daily pain and stool diaries for 2 weeks. Participants were assigned IBS subtypes based on their reported stool information, per adult Rome III criteria. IBS subtypes were compared for demographic variables and pain characteristics. Results IBS with constipation (IBC-C) was the most common subtype of the disorder (58.1% of subjects), whereas mixed IBS (IBS-M) was the least common (2.3% of subjects); 34.1% of subjects were unsubtyped (IBS-U) and 5.4% had IBS with diarrhea (IBS-D). The groups of different IBS subtypes did not differ significantly by sex, age, ethnicity, or pain characteristics. Conclusions In contrast to adults, IBS-C and IBS-U are the most common subtypes of IBS in children, whereas IBS-D and IBS-M are less common. Demographic and pain characteristics cannot distinguish subtypes.
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Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
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OBJECTIVES:The objective of this study was to investigate whether ingestion of fructose and fructans (such as inulin) can exacerbate irritable bowel syndrome (IBS) symptoms. The aim was to better understand the origin of these symptoms by magnetic resonance imaging (MRI) of the gut. A total of 16 healthy volunteers participated in a four-way, randomized, single-blind, crossover study in which they consumed 500 ml of water containing 40 g of either glucose, fructose, inulin, or a 1:1 mixture of 40 g glucose and 40 g fructose. MRI scans were performed hourly for 5 h, assessing the volume of gastric contents, small bowel water content (SBWC), and colonic gas. Breath hydrogen (H2) was measured and symptoms recorded after each scan.RESULTS:Data are reported as mean (s.d.) (95% CI) when normally distributed and median (range) when not. Fructose increased area under the curve (AUC) from 0-5 h of SBWC to 71 (23) l/min, significantly greater than for glucose at 36 (11-132) l/min (P<0.001), whereas AUC SBWC after inulin, 33 (17-106) l/min, was no different from that after glucose. Adding glucose to fructose decreased AUC SBWC to 55 (28) l/min (P=0.08) vs. fructose. Inulin substantially increased AUC colonic gas to 33 (20) l/min, significantly greater than glucose and glucose+fructose (both P<0.05). Breath H2 rose more with inulin than with fructose. Glucose when combined with fructose significantly reduced breath H2 by 7,700 (3,121-12,300) p.p.m./min relative to fructose alone (P<0.01, n=13).CONCLUSIONS:Fructose but not inulin distends the small bowel with water. Adding glucose to fructose reduces the effect of fructose on SBWC and breath hydrogen. Inulin distends the colon with gas more than fructose, but causes few symptoms in healthy volunteers.Am J Gastroenterol advance online publication, 19 November 2013; doi:10.1038/ajg.2013.386.
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Profiling phylogenetic marker genes, such as the 16S rRNA gene, is a key tool for studies of microbial communities but does not provide direct evidence of a community's functional capabilities. Here we describe PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states), a computational approach to predict the functional composition of a metagenome using marker gene data and a database of reference genomes. PICRUSt uses an extended ancestral-state reconstruction algorithm to predict which gene families are present and then combines gene families to estimate the composite metagenome. Using 16S information, PICRUSt recaptures key findings from the Human Microbiome Project and accurately predicts the abundance of gene families in host-associated and environmental communities, with quantifiable uncertainty. Our results demonstrate that phylogeny and function are sufficiently linked that this 'predictive metagenomic' approach should provide useful insights into the thousands of uncultivated microbial communities for which only marker gene surveys are currently available.
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A 16S rRNA gene database (http://greengenes.lbl.gov) addresses limitations of public repositories by providing chimera screening, standard alignment, and taxonomic classification using multiple published taxonomies. It was found that there is incongruent taxonomic nomenclature among curators even at the phylum level. Putative chimeras were identified in 3% of environmental sequences and in 0.2% of records derived from isolates. Environmental sequences were classified into 100 phylum-level lineages in the Archaea and Bacteria.
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Carbohydrates occur across a range of foods regularly consumed including grains such as wheat and rye, vegetables, fruits, and legumes. Short-chain carbohydrates with chains of up to 10 sugars vary in their digestibility and subsequent absorption. Those that are poorly absorbed exert osmotic effects in the intestinal lumen increasing its water volume, and are rapidly fermented by bacteria with consequent gas production. These two effects alone may underlie most of the induction of gastrointestinal symptoms after they are ingested in moderate amounts via luminal distension in patients with visceral hypersensitivity. This has been the basis of the use of lactose-free diets in those with lactose malabsorption and of fructose-reduced diets for fructose malabsorption. However, application of such dietary approaches in patients with functional bowel disorders has been restricted to observational studies with uncertain efficacy. As all dietary poorly absorbed short-chain carbohydrates have similar and additive effects in the intestine, a concept has been developed to regard them collectively as FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) and to evaluate a dietary approach that restricts them all. In patients with irritable bowel syndrome, there is now an accumulating body of evidence, based on observational and comparative studies, and on randomized-controlled trials that supports the notion that FODMAPs trigger gastrointestinal symptoms in patients with functional bowel disorders, and that a diet low in FODMAPs offers considerable symptom relief in the majority of patients who use it.Am J Gastroenterol advance online publication, 16 April 2013; doi:10.1038/ajg.2013.96.
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Background Sub-acute ruminal acidosis (SARA) is a well-recognized digestive disorder found in particular in well-managed dairy herds. SARA can result in increased flow of fermentable substrates to the hindgut, which can increase the production of volatile fatty acids, alter the structure of the microbial community, and have a negative effect on animal health and productivity. However, little is known about changes in the structure of the microbial community and its relationship with fatty acids during SARA. Four cannulated primiparous (60 to 90 day in milk) Holstein dairy cows were assigned to two diets in a 2 × 2 crossover experimental design. The diets contained (on a dry matter basis): 40% (control diet, COD) and 70% (SARA induction diet, SAID) concentrate feeds. Samples of ruminal fluid and feces were collected on day 12, 15, 17 and 21 of the treatment period, and the pH was measured in the ruminal and fecal samples; the fecal microbiota was determined by pyrosequencing analysis of the V1–V3 region of amplified 16S ribosomal RNA (16S rRNA). Results SAID decreased ruminal and fecal pH and increased the propionate, butyrate and total volatile fatty acid (TVFA) concentration in feces when compared with the COD. A barcoded DNA pyrosequencing method was used to generate 2116 16S operational taxonomic units (OTUs). A total of 11 phyla were observed, distributed amongst all cattle on both diets; however, only 5 phyla were observed in all animals regardless of dietary treatment, and considerable animal to animal variation was revealed. The average abundance and its range of the 5 phyla were as follows: Firmicutes (63.7%, 29.1–84.1%), Proteobacteria (18.3%, 3.4–46.9%), Actinobacteria (6.8%, 0.4–39.9%), Bacteroidetes (7.6%, 2.2–17.7%) and Tenericutes (1.6%, 0.3–3%). Feeding the SAID resulted in significant shifts in the structure of the fecal microbial community when compared with the traditional COD. Among the 2116 OTUs detected in the present study, 88 OTUs were affected significantly by diet; and the proportion of these OTUs was 20.6% and 17.4% among the total number of sequences, respectively. Among the OTUs affected, the predominant species, including OTU2140 (G: Turicibacter), OTU1695 (G: Stenotrophomonas) and OTU8143 (F: Lachnospiraceae), were increased, while the abundance of OTU1266 (S: Solibacillus silvestris) and OTU2022 (G: Lysinibacillus) was reduced in the SAID group compared with the COD. Further, our results indicated that the fecal volatile fatty acid (VFA) concentrations were significantly related to presence of some certain species of Bacteroidetes and Firmicutes in the feces. Conclusions This is, to our knowledge, the first study that has used barcoded DNA pyrosequencing to survey the fecal microbiome of dairy cattle during SARA. Our results suggest that particular bacteria and their metabolites in the feces appear to contribute to differences in host health between those given SAID and traditional COD feeding. A better understanding of these microbial populations will allow for improved nutrient management and increased animal growth performance.
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Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat's signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81-99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.
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Bacteria that colonize the mammalian intestine collectively possess a far larger repertoire of degradative enzymes and metabolic capabilities than their hosts. Microbial fermentation of complex non-digestible dietary carbohydrates and host-derived glycans in the human intestine has important consequences for health. Certain dominant species, notably among the Bacteroidetes, are known to possess very large numbers of genes that encode carbohydrate active enzymes and can switch readily between different energy sources in the gut depending on availability. Nevertheless, more nutritionally specialized bacteria appear to play critical roles in the community by initiating the degradation of complex substrates such as plant cell walls, starch particles and mucin. Examples are emerging from the Firmicutes, Actinobacteria and Verrucomicrobium phyla, but more information is needed on these little studied groups. The impact of dietary carbohydrates, including prebiotics, on human health requires understanding of the complex relationship between diet composition, the gut microbiota and metabolic outputs.
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