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Effect of chicory-derived inulin-type fructans on abundance of Bifidobacterium and on bowel function: a systematic review with meta-analyses
Critical Reviews In Food Science and Nutrition
Abstract
Inulin-type fructans are considered to stimulate the growth of beneficial microorganisms, like Bifidobacterium in the gut and support health. However, both the fructan source and chemical structure may modify these effects. A systematic review was conducted to assess the effects of chicory-derived inulin-type fructans consumed either in specific foods or as dietary supplements on abundance of Bifidobacterium in the gut and on health-related outcomes. Three electronic databases and two clinical trial registries were systematically searched until January 2021. Two authors independently selected randomized controlled trials that investigated with a protocol of minimum seven days supplementation the effect of chicory-derived inulin-type fructans on Bifidobacterium abundance in any population. Meta-analyses with random-effects model were conducted on Bifidobacterium abundance and bowel function parameters. We evaluated risk of bias using Cochrane RoB tool. Chicory-derived inulin-type fructans at a dose of 3–20 g/day significantly increased Bifidobacterium abundance in participants with an age range from 0 to 83 years (standardized mean difference: 0.83, 95% CI: 0.58–1.08; p < 0.01; 50 studies; 2525 participants). Significant bifidogenic effects were observed in healthy individuals and in populations with health impairments, except gastrointestinal disorders. Significant beneficial effects on bowel function parameters were observed in healthy subjects. Chicory-derived inulin-type fructans may have significant bifidogenic effects and may beneficially influence bowel function in healthy individuals. PROSPERO registration number CRD42020162892.
... The inulin product used in this study was extracted from chicory root, comprising approximately 90% long-chain fructan (inulin) and 10% monosaccharides, disaccharides, and oligosaccharides. Numerous studies have reported the prebiotic properties of inulin, particularly its effects on promoting the growth of Bifidobacteria and Lactobacilli [45,46]. Lactobacilli were shown to present at lower counts in the gut microbiota of formula-fed infants compared to their breastfed counterparts [12][13][14], meriting inulin supplementation in infant formula. ...
... These factors reduce colonic Fe absorption and dilute its concentration in digesta and feces. In support of this, a recent meta-analysis of 14 randomized controlled studies involving participants of all age groups identified an increase in stool frequency as a significant gastrointestinal effect of dietary supplementation with chicory-derived inulin-type fructan [46,49]. Although this increase was not statistically significant in the subgroup analysis of 5 studies conducted with formula-fed infants [46,49], it should be noted that the doses of long-chain inulin contained in the prebiotic supplements varied across these studies [23,[49][50][51][52]. Increasing stool frequency was also recognized as an outcome of consuming native chicory inulin, as concluded by the European Food Safety Authority after reviewing 6 studies involving 86 subjects who consumed !12 g of inulin per day [53]. ...
... In support of this, a recent meta-analysis of 14 randomized controlled studies involving participants of all age groups identified an increase in stool frequency as a significant gastrointestinal effect of dietary supplementation with chicory-derived inulin-type fructan [46,49]. Although this increase was not statistically significant in the subgroup analysis of 5 studies conducted with formula-fed infants [46,49], it should be noted that the doses of long-chain inulin contained in the prebiotic supplements varied across these studies [23,[49][50][51][52]. Increasing stool frequency was also recognized as an outcome of consuming native chicory inulin, as concluded by the European Food Safety Authority after reviewing 6 studies involving 86 subjects who consumed !12 g of inulin per day [53]. ...
Background
Infant formula in the United States contains abundant iron, raising health concerns about excess iron intake in early infancy.
Objectives
Using a piglet model, we explored the impact of high iron fortification and prebiotic or synbiotic supplementation on iron homeostasis and trace mineral bioavailability.
Methods
Twenty-four piglets were stratified and randomly assigned to treatments on postnatal day 2. Piglets were individually housed and received an iron-adequate milk diet (AI), a high-iron milk diet (HI), HI supplemented with 5% inulin (HI with a prebiotic [HIP]), or HIP with an oral gavage of Ligilactobacillus agilis YZ050, an inulin-fermenting strain, every third day (HI with synbiotic [HIS]). Milk was provided in 14 meals daily, mimicking formula feeding in infants. Fecal consistency score and body weight were recorded daily or every other day. Blood and feces were sampled weekly, and tissues collected on postnatal day 29. Data were analyzed using mixed model analysis of variance with repeated measures whenever necessary.
Results
Diet did not affect growth. HI increased hemoglobin, hematocrit, and serum iron compared to AI. Despite marginal adequacy, AI upregulated iron transporter genes and maintained satisfactory iron status in most pigs. HI upregulated hepcidin gene expression in liver, caused pronounced tissue iron deposition, and markedly increased colonic and fecal iron. Inulin supplementation, regardless of L. agilis YZ050, not only attenuated hepatic iron overload but also decreased colonic and fecal iron without altering pH or the expression of iron regulatory genes. HI lowered zinc (Zn) and copper (Cu) in the duodenum and liver compared to AI, whereas HIP and HIS further decreased Zn and Cu in the liver and diminished colonic and fecal trace minerals.
Conclusions
Early-infancy excessive iron fortification causes iron overload and compromises Zn and Cu absorption. Inulin decreases trace mineral absorption likely by enhancing gut peristalsis and stool frequency.
... Inulin-type fructans (ITFs) are a type of prebiotic, and are storage carbohydrates in many plants and fruits such as onion, wheat, and Jerusalem Artichoke. ITFs belong to linear polydisperse carbohydrates linked by β-(2-1) glycosidic linkages, and their industrial production is mainly from chicory (Cichorium intybus) roots [87]. Based on the distribution of chain lengths and the mode of production, ITFs can be classified as inulin and oligofructose. ...
... Various studies have reported the functions of ITFs for infants, especially at a higher dosage, such as for the gut microbiota composition and prevention from infections [67,87,88]. In 2011-2013, ClinicalTrials (ClinicalTrials.gov) ...
Human milk contains an abundance of nutrients which benefit the development and growth of infants. However, infant formula has to be used when breastfeeding is not possible. The large differences between human milk and infant formula in prebiotics lead to the suboptimal intestinal health of infant formula-fed infants. This functional deficit of infant formula may be overcome through other dietary polysaccharides that have been characterized. The aim of this review was to summarize the potential applications of dietary polysaccharides as prebiotics, synbiotics, and postbiotics in infant formula to better mimic the functionality of human milk prebiotics for infant gut health. Previous studies have demonstrated the influences of dietary polysaccharides on gut microbiota, SCFA production, and immune system development. Compared to prebiotics, synbiotics and postbiotics showed better application potential in shaping the gut microbiota, the prevention of pathogen infections, and the development of the immune system. Moreover, the safety issues for biotics still require more clinical trials with a large-scale population and long time duration, and the generally accepted regulations are important to regulate related products. Pectin polysaccharides has similar impacts to human milk oligosaccharides on gut microbiota and the repairing of a damaged gut barrier, with similar functions also being observed for inulin and β-glucan. Prebiotics as an encapsulation material combined with probiotics and postbiotics showed better potential applications compared to traditional material in infant formula.
... 22 Conversely, inulin-type fructan consumption is associated with increased fecal abundance of bifidobacteria. 23,24 Given that commensal bifidobacteria serve as biomarkers of healthy gut microbial metabolism and immunity, 25 and the established metabolic and GI health benefits of inulin and prebiotic FOS, 24,[26][27][28] new approaches beyond FODMAP elimination diets are warranted to mitigate symptoms of FODMAP sensitivity. ...
... 22 Conversely, inulin-type fructan consumption is associated with increased fecal abundance of bifidobacteria. 23,24 Given that commensal bifidobacteria serve as biomarkers of healthy gut microbial metabolism and immunity, 25 and the established metabolic and GI health benefits of inulin and prebiotic FOS, 24,[26][27][28] new approaches beyond FODMAP elimination diets are warranted to mitigate symptoms of FODMAP sensitivity. ...
BACKGROUND AND AIMS: Dietary fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) contribute to gastrointestinal (GI) symptoms in individuals with FODMAP sensitivity and/or irritable bowel syndrome (IBS). Oral enzyme supplementation is a strategy to reduce dietary FODMAP exposure and limit FODMAP-associated GI distress. This clinical trial investigated the safety of dietary supplementation with a food-grade, microbial inulinase known to hydrolyze fructan-type or inulin-type FODMAPs and related fructo-oligosaccharides (FOS) in vitro. METHODS: A randomized, double-blind, placebo-controlled, parallel design trial was conducted in 60 healthy adult participants of both sexes. Following a 2-week run-in placebo phase, participants were randomized to consume inulinase or placebo capsules twice daily with meals for 4 weeks. The total daily dose of inulinase was 2,000 inulinase activity units (INU). Safety measures included blood clinical chemistry, hematology, lipid profile, high-sensitivity C-reactive protein (hs-CRP), insulin, lactate, and uric acid. GI symptoms were recorded weekly using the 15-item Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: Fifty-eight participants completed the study. There were no clinically meaningful between-group differences in blood biomarkers. During the 4-week intervention period, 5 (16.7%) of 30 participants reported 5 adverse events (AEs) in the inulinase group, and 8 (26.7%) of 30 participants reported 13 AEs in the placebo group. No statistically significant between-group differences were observed in the change from baseline to 1, 2, 3, or 4 weeks of supplementation with respect to GSRS overall or domain scores. CONCLUSIONS: Microbial inulinase supplementation demonstrated a favorable safety profile in healthy adults. Further investigation in a dose-ranging study in individuals with dietary FODMAP, fructan, or inulin sensitivity or IBS is warranted. ClinicalTrials.gov: NCT05744700.
... Even though, a clear maximum microbial net growth (A parameter of 3.50 log CFU ml −1 ) was obtained for L. plantarum 299v with MRS broth (Fig. 1 It is well known that inulin is a good prebiotic and enhances the probiotics' growth. [36][37][38][39] The probiotics studied adapted better to the medium supplemented with inulin than those with chia mucilage. The A values of WIn1% (Lacticaseibacillus casei Shirota and B. lactis BPL1) and WIn2% (Lactiplantibacillus plantarum 299v) were signicantly higher (p < 0.05) than the WMc1% and WMc2% medium. ...
... In previous investigations with B. lactis BPL1 have reported the stimulation of Bidobacterium species in culture media containing inulin. 37,38 However, the concentration of inulin should be evaluated since high concentrations may cause adverse effects on Bidobacterium growth. McLaughlin et al. 36 reported that several species of Bidobacterium did not grow adequately at high concentrations (>5% w/v) of inulin. ...
Postbiotics have gained attention due to their health benefits and potential bioactive metabolites. Short-chain fatty acids (SCFAs) have been identified within these metabolites, which are related to anti-inflammatory properties and antioxidant activity, among others. For the food industry, it is important to consider a suitable culture medium for postbiotic production. Whey, as a by-product from the cheese industry, is rich in nutrients and is proposed to support this purpose. This study is aimed to evaluate the microbial growth of three probiotics, Lactiplantibacillus plantarum 299v, Lacticaseibacillus casei Shirota, and Bifidobacterium animalis subsp. lactis BPL1, using a whey culture medium supplemented with soluble fibres (inulin or chia mucilage) at two concentrations (1% or 2% w/w). Also, analyse the effect of soluble fibres on the production of SCFAs and the antioxidant activity of cell-free supernatant as postbiotics. SCFA production was quantified by HPLC and antioxidant activity was determined by the DPPH⁺ assay and the KMnO4 agar method. The formulated culture media promoted the growth of probiotics, especially those added with inulin. Lactiplantibacillus plantarum 299v and Lacticaseibacillus casei Shirota produced primary lactic and acetic acid. B. lactis BPL1 had the highest SCFAs production in the culture medium with 2% w/w of inulin. The antioxidant activity from Lactiplantibacillus plantarum 299v postbiotics was significantly improved with soluble fibres (p < 0.05). This study shows postbiotics are produced with a sustainable approach. Moreover, postbiotics based on whey and soluble fibres can be a potential ingredient for the formulation of new food products as sources of SCFAs and antioxidants.
... A prebiotic is "a substrate that is selectively utilized by host microorganisms, conferring a health benefit" (Gibson et al., 2017). Inulin-type fructans (ITFs), plant-stored polysaccharides consisting of β-(2-1)linked fructose residues, are among the most studied prebiotic fibers that can promote the growth of beneficial gut bacteria (Nagy et al., 2022;Vandeputte et al., 2017). ITFs are mainly produced from chicory roots and can be separated into inulin [degree of polymerization (DP) 2-60], short-chain fructooligosaccharides , and oligofructose (DP < 10). ...
... The bifidogenic effects of ITFs have been well established, as ITFs increase the abundance of Bifidobacterium spp. Bifidobacterium are believed to have numerous health-promoting effects, including the maintenance of gut epithelial integrity and modulating immune responses (Nagy et al., 2022). Evidence exists on the key role of gut microbiota in the development of IR in PCOS (He & Li, 2020). ...
Polycystic ovary syndrome (PCOS) is associated with reproductive disorders and adverse cardiometabolic risk factors that can negatively impact the general health of women. Inulin‐type fructans (ITFs) are proposed to beneficially affect risk factors associated with metabolic disorders. Whether ITFs can help with the management of PCOS by modifying insulin resistance (IR) and androgen levels has not yet been explored. The aim of this study was to investigate the effects of ITFs with different degrees of polymerization on insulin resistance, blood lipids, anthropometric measures, and hormonal status in overweight and obese women with PCOS. In a randomized double‐blind placebo‐controlled trial, seventy‐five women with PCOS aged 18–40 years old were randomly assigned to receive 10 g/day of high‐performance inulin (HPI) or oligofructose‐enriched inulin (OEI) or maltodextrin for 12 weeks. Biochemical and clinical outcomes were measured at baseline and after the intervention. Participants in the HPI and OEI groups experienced improvements in waist circumference, total testosterone, free androgen index, sex hormone‐binding globulin, and triglycerides compared to the placebo group. Also, the number of women with irregular menses or oligomenorrhoea decreased significantly in both ITF groups. Participants in the HPI group reported lower body mass, fasting insulin, and HOMA‐IR, as well as a higher quantitative insulin sensitivity check index. ITF supplementation, especially with long‐chain ITFs, when given for 12 weeks may improve metabolic outcomes, androgen status and clinical manifestations in women with PCOS.
... On the other hand, inulin have also been reported as a bi dogenic factor as it enhances the growth of bi dobacteria in the intestine of human as well as in animals (Nagy et al. 2023). A team of scientist have evaluated the bi dogenic effect of the blend of inulin and polydextrose by in vitro fermentation of 15 inoculates of human feces which showed that the blend has shown reduced gas production and bi dogenic effect with abundance of bene cial microbes such as Faecalibacterium and Roseburia (Zhu et al. 2022). ...
Inulin, a naturally occurring storage polysaccharide, boasts a broad spectrum of applications in the realms of both food and pharmaceutical industries. Inulin is a soluble dietary fiber found widely in plants, primarily derived from various plant sources. Acknowledged as a reserve biopolysaccharide in plants, it attains status as an indigestible carbohydrate owing to its unique β-(2,1)-glycosidic bond structure. Given its ubiquitous presence in nature and its pivotal role in various industries, there has been a growing focus on the extraction, isolation, and characterization of inulin in recent years. Recent studies, both in animals and humans, have demonstrated that functional inulin exhibits a range of bioactivities, including immunomodulation, antioxidant properties, antitumor effects, hepatoprotection, hypoglycemic effects, and gastrointestinal protection. The growing popularity of inulin has led to an increased consumption of foods containing this compound. Additionally, inulin is promising as a bioactive substance for the development of various food products. The initial segment of this chapter provides a comprehensive overview of the fundamental features of inulin. This includes an exploration of its production, applications in industries such as food and cosmetics, its positive impact on human health, and its primary nutraceutical properties. Special attention is given to delving into the techniques employed for the extraction and purification of inulin. The objective is to establish a theoretical foundation for further advancements in the preparation and utilization of inulin in pharmaceutical fields. This chapter endeavors to elucidate the myriad and interconnected roles of inulin, highlighting its crucial contributions to the progress of healthcare and biomedicine. It delves into the recent advancements made in inulin-based therapeutics, culminating in a discussion that draws valuable insights into the prospects and opportunities within the realm of inulin applications.
... in vivo and in vitro studies have demonstrated that supplementation of inulin and oligofructose substantially alters the composition of gut microbiota by promoting the growth of Bifidobacteria and Lactobacilli(Nagy et al., 2023;Seesaha et al., 2020). A greater Bifidobacteria concentration in the gut has been regarded as a marker of intestinal health(Roberfroid et al., 2010). ...
Inulin fructans are non-digestible polysaccharides of the fructan family that are composed of monomers of fructose joined by β-(2-1) glycosidic (fructosyl-fructose) linkages with varying degrees of polymerization. Inulin fructan has numerous functional and health benefits, which have fueled market demand remarkably as a functional food ingredient during the last several years. Recent human and animal clinical trials have revealed that inulin can enhance the saccharolytic fermentation over proteolytic fermentation in the colon, thereby increasing short-chain fatty acid and lactic acid production, which in turn deliver numerous health benefits, including gut microflora modulation, enhancing mineral absorption and reducing the risk of colon cancers. With the rising popularity and use of inulin, there has been increasing research interest in determining the quality and quantity of inulin fructans. Quantification of inulin has become challenging since plants contain inulin with a varying degree of polymerization in a range of 3-60. Various techniques have been used to quantify fructans, including diverse chromatographic and enzyme-involved spectrometric techniques. Despite there are many reviews on inulin as a functional food, few compiles accepted quantification methods of inulin. This review offers a concise guide on the theoretical principles behind the accepted analytical methods of quantification of inulin, in addition to the fermentability of inulin in the human colon and its potential health benefits.
... Inulin, erythritol, and xylitol were chosen as osmotic actives as healthier alternatives to sucrose, which is one of the most commonly used components in studies on osmotic dehydration. Compared to sucrose, these ingredients have a lower energy value, do not significantly elevate blood glucose levels, do not cause dental caries, and have broad beneficial effects on health, including prebiotic properties, lowering triglycerides, anti-inflammatory properties, and reducing energy intake, among others [65][66][67][68][69]. The use of these osmotically active substances seems reasonable due to the adverse health effects of sucrose, including an increased risk of metabolic diseases [70], the prevalence of depression [71], or periodontal diseases [72]. ...
Osmotic dehydration as a process of removing water from food by immersing the raw material in a hypertonic solution is used primarily to extend the shelf life of products and as a pretreatment before further processing steps, such as drying and freezing. However, due to the bi-directional mass transfer that occurs during osmotic dehydration, the process can also be used to shape sensory properties and enrich the plant matrix with nutrients. The purpose of this study was to evaluate the effect of osmotic dehydration on the absorption of potassium by beet pulp immersed in various hypertonic solutions (sucrose, inulin, erythritol, xylitol solutions) with the addition of three chemical forms of potassium (gluconate, citrate, chloride) using variable process conditions. The study proved that osmotic dehydration is an effective way to enrich food. The highest potassium content (5779.03 mg/100 g) was found in a sample osmotically dehydrated in a 50% erythritol solution with 5.0% potassium chloride addition with a process that lasted 180 min and took place at 30 °C. The results obtained indicate the high potential of osmotic dehydration in improving the health values of food products. In addition, the antioxidant activity and proximate composition of osmotically dehydrated samples were also characterized in this study.
... Unexpectedly, lcFOS, a bifidogenic oligosaccharide commonly used for both adults and infants [44], had little effect on infant-type HRB in this study. Considering the cause of this, all subjects were under one year of age, and although some had started to consume solid foods, they generally had little feeding experience with fructans, which are often derived from vegetables and fruits. ...
Background: The gut microbiota of breast-fed infants is dominated by infant-type human-residential bifidobacteria (HRB) that contribute to infant health; thus, it is crucial to develop infant formulas that promote the establishment of a gut microbiota enriched with infant-type HRB, closely resembling that of breastfed infants. Methods: We compared various non-digestible prebiotic oligosaccharides and their combinations using a fecal culture system to explore which candidates could promote the growth of all infant-type HRB and rarely yield non-responders. The analysis included lactulose (LAC), raffinose (RAF), galactooligosaccharides (GOS), and short- and long-chain fructooligosaccharides. Fecal samples were collected from seven infants aged 1.5–10.2 months and cultured with each oligosaccharide individually or their combinations. Results: No single oligosaccharide effectively promoted the growth of all infant-type HRB, although GOS promoted the growth of HRB other than Bifidobacterium longum subsp. longum. Only the LAC/RAF/GOS group evenly and effectively promoted the growth of all infant-type HRB. Accordingly, acetate production was higher in fecal cultures supplemented with GOS or LAC/RAF/GOS than in the other cultures, suggesting that it is a superior combination for all infant-type HRB and rarely yields non-responders. Conclusions: This study can aid in developing infant formulas that help align the gut microbiota of formula-fed infants with that of breastfed infants.
... Infant breast milk and adult diets contain a high abundance of glycans and oligosaccharides with complex structures that cannot be digested by the human body and hence pass through the large intestine as substrates for the gut microbiota. Bifidobacteria metabolize monosaccharides, disaccharides, and oligosaccharides; however, different bifidobacterial species prefer dietary glycans, including inulin-type fructan (ITF) 13,14 , resistant starch (RS) 15 , galactan 16,17 , xylan 18,19 , and arabinan 20 , while others utilize host-derived glycans, such as human milk oligosaccharides (HMOs) 21,22 and mucins 23 . ...
Throughout the life span of a host, bifidobacteria have shown superior colonization and glycan abilities. Complex glycans, such as human milk oligosaccharides and plant glycans, that reach the colon are directly internalized by the transport system of bifidobacteria, cleaved into simple structures by extracellular glycosyl hydrolase, and transported to cells for fermentation. The glycan utilization of bifidobacteria introduces cross-feeding activities between bifidobacterial strains and other microbiota, which are influenced by host nutrition and regulate gut homeostasis. This review discusses bifidobacterial glycan utilization strategies, focusing on the cross-feeding involved in bifidobacteria and its potential health benefits. Furthermore, the impact of cross-feeding on the gut trophic niche of bifidobacteria and host health is also highlighted. This review provides novel insights into the interactions between microbe-microbe and host-microbe.
... (2022),Paula et al. (2015),Teferra, (2021),Nagy et al. (2022) y ref. cit). Sus propiedades de modificación reológica del agua, su capacidad de formar geles y la percepción "cremosa" que confiere a alimentos lo posicionan como un agente texturizante y funcional en la elaboración de alimentos, así como sustituto de sustancias grasas (queso, chocolate, etc) (cf.: Xuemei Zhou et al.(2023), Jackson et al. (2023), Paula et al. (2015), Nobre et al. (2015), Sudha et al. (2022), Mudannayake et al. (2022), Pérez-López et al. (2020) y ref. cit). ...
Yacon (Smallanthus sonchifollius (Poepp.) H. Rob), a little-known tubber was studied for fructan extraction (87.7%), ethanolic fermentation (5.5-6.5% (vol.)), acetic fermentation (pH=3.21-3.82), foam-mat drying (constant rate 4 times faster, final humidity 7 times lower in half the time when compared to the non-foamed product), as well as texturizing agent in dairy products. We uncovered over 3000 foreign patents that represent barriers for the industrialization of yacon. A content- based analysis of the patent is presented. 83.02% of the patents belong to China, Korea, Japan and Rusia. In almost 17% of the cases, yacon is the direct object of the patent. 59% of the patents are related to foods.
... Interestingly, the consumption of the cranberry extract successfully modulated the fecal microbiota of the participants included in this study with a strong bifidogenic effect. This effect is commonly associated with supplementation of prebiotic fibers, such as inulin and fructooligosaccharides, as first reported by Gibson & Roberfroid 37 and confirmed by many other studies [38][39][40][41][42] . In the present study, Bifidobacterium was significantly increased with the cranberry extract providing low amounts of (poly)phenols (109.3 mg/day) and oligosaccharides (125 mg/day, mainly arabinoxyloglucan). ...
Cranberry is associated with multiple health benefits, which are mostly attributed to its high content of (poly)phenols, particularly flavan-3-ols. However, clinical trials attempting to demonstrate these positive effects have yielded heterogeneous results, partly due to the high inter-individual variability associated with gut microbiota interaction with these molecules. In fact, several studies have demonstrated the ability of these molecules to modulate the gut microbiota in animal and in vitro models, but there is a scarcity of information in human subjects. In addition, it has been recently reported that cranberry also contains high concentrations of oligosaccharides, which could contribute to its bioactivity. Hence, the aim of this study was to fully characterize the (poly)phenolic and oligosaccharidic contents of a commercially available cranberry extract and evaluate its capacity to positively modulate the gut microbiota of 28 human subjects. After only four days, the (poly)phenols and oligosaccharides-rich cranberry extract, induced a strong bifidogenic effect, along with an increase in the abundance of several butyrate-producing bacteria, such as Clostridium and Anaerobutyricum. Plasmatic and fecal short-chain fatty acids profiles were also altered by the cranberry extract with a decrease in acetate ratio and an increase in butyrate ratio. Finally, to characterize the inter-individual variability, we stratified the participants according to the alterations observed in the fecal microbiota following supplementation. Interestingly, individuals having a microbiota characterized by the presence of Prevotella benefited from an increase in Faecalibacterium with the cranberry extract supplementation.
... However, these traits depend on producing the right enzymes, making them strain-specific [150]. Numerous studies have shown that inulin is bifidogenic in all age group participants [151]. A case study revealed that type 2 diabetes patients who took inulin-type fructans supplements daily noticed a slight but substantial increase in fecal Bifidobacteria levels [152]. ...
In recent years, inulin has gained much attention as a promising multifunctional natural biopolymer with numerous applications in drug delivery, prebiotics, and therapeutics. It reveals a multifaceted biopolymer with transformative implications by elucidating the intricate interplay between inulin and the host, microbiome, and therapeutic agents. Their flexible structure, exceptional targetability, biocompatibility, inherent ability to control release behavior, tunable degradation kinetics, and protective ability make them outstanding carriers in healthcare and biomedicine. USFDA has approved Inulin as a nutritional dietary supplement for infants. The possible applications of inulin in biomedicine research inspired by nature are presented. The therapeutic potential of inulin goes beyond its role in prebiotics and drug delivery. Recently, significant research efforts have been made towards inulin's anti-inflammatory, antioxidant, and immunomodulatory properties for their potential applications in treating various chronic diseases. Moreover, its ability to reduce inflammation and modulate immune responses opens new avenues for treating conditions such as autoimmune disorders and gastrointestinal ailments. This review will attempt to illustrate the inulin's numerous and interconnected roles, shedding light on its critical contributions to the advancement of healthcare and biomedicine and its recent advancement in therapeutics, and conclude by taking valuable insights into the prospects and opportunities of inulin.
... Inulin's prebiotic activity has been extensively demonstrated in numerous studies, showing selective fermentation by bifidogenic bacteria [8,9]. Several meta-analyses have confirmed the positive effects of inulin on the colonic microbiome and stool frequency in patients with functional constipation and IBS-C [10][11][12][13]. The prescription of a diet rich in dietary fibers is a typical treatment approach for patients with IBS-C and has been proven to be effective [14]. ...
Background
Constipation-predominant irritable bowel syndrome (IBS-C) mainly affects females, and dietary interventions for symptom relief often yield poor results because of low patient adherence. The development of functional food products enriched with dietary fibers may increase patients’ adherence to a healthy diet and relieve IBS-С symptoms.
Objective
This proof-of-concept, open-label, randomized controlled pilot study is aimed to evaluate the efficacy of kombucha enriched with inulin and vitamins in females with IBS-C.
Methods
Forty females with IBS-C were randomly assigned to receive either 220 mL of kombucha enriched with inulin (2.53 g/220 mL) and vitamins (B1 – 0.59 mg, B2 – 0.55 mg, B3 – 5.9 mg, B6 – 0.7 mg, and folic acid – 81.4 μg/220 mL) or water for 10 d. Stool frequency, Bristol stool scale score (BSSS), and abdominal symptoms were evaluated using a 5-point Likert scale on days 5, 9 and 14 of the study. The palatability of the drink was assessed using a visual analog scale.
Results
After 10 d, the kombucha group showed a significant increase in stool frequency (0.60 ± 0.31–0.85 ± 0.19 times/d; P = 0.004) compared with the control (0.63 ± 0.33 compared with 0.72 ± 0.28; P = 0.6). The mean values of the BSSS increased in the kombucha group (3.0 ± 1.2–4.4 ± 1.0; P = 0.001), whereas they remained unchanged in the control (2.9 ± 1.2 compared with 3.4 ± 1.2; P = 0.6). The kombucha group also experienced a significant decrease in the feeling of incomplete bowel emptying (1.88 ± 0.78 compared with 1.41 ± 0.56 points; P = 0.015), which was not observed in the control group.
Conclusions
Short-term consumption of kombucha enriched with inulin and vitamins was associated with an increase in stool frequency, an improvement in the BSSS, and a reduction in the feeling of incomplete bowel emptying in females with IBS-C. Further large-scale clinical trials investigating the efficacy of kombucha enriched with inulin and vitamins in patients with IBS-C are warranted to prove the observed effects.
Trial registration number
This trial was registered at clinicaltrials.gov as NCT05164861 (==https://clinicaltrials.gov/study/NCT05164861?term=NCT05164861&rank=1; registered on 18 December, 2021).
... 141 Chicory-derived inulin-type fructans (ITFs) significantly increased the abundance of members of the genus Bifidobacterium in the human gut. 142 Aldubayan et al. also found that ITFs selectively increased Bifidobacterium and Faecalibacterium in overweight or obese individuals. 143 Xiong et al. found that ITFs increased the Firmicutes/Bacteroidetes (F/B) ratio and improved the gut microbial composition in peritoneal dialysis patients. ...
The vital role of probiotics in the food field has been widely recognized, and at the same time, probiotics are gradually exhibiting surprising effects in the field of nutraceuticals, especially in regulating gut inflammation and the nutritional environment. As a dietary supplement in clinical nutrition, the coadministration of probiotics with antibiotics model has been applied to prevent intestinal infections caused by Clostridioides difficile. However, the mechanism behind this "bacteria-drug combination" model remains unclear. In particular, the selection of specific probiotic strains, the order of probiotics or antibiotics, and the time interval of coadminis-tration are key issues that need to be further explored and clarified. Here, we focus on the issues mentioned above and give reasonable opinions, mainly including: (1) probiotics are safer and more effective when they intervene after antibiotics have been used; (2) the choice of the time interval between coadministration should be based on the metabolism of antibiotics in the host, differences in probiotic strains, the baseline ecological environment of the host's intestine, and the host immune level; in addition, the selection of the coadministra-tion regime should also take into account factors such as the antibiotic sensitivity of probiotics and dosage of probiotics; and (3) by encapsulating probiotics, combining probiotics with prebiotics, and developing next-generation probiotics (NGPs) and postbiotic formulations, we can provide a more reasonable reference for this type of "bacteria-drug combination" model, and also provide targeted guidance for the application of probio-tic dietary supplements in the antibiotic management of C. difficile infection.
... Several clinical trials of inulin supplementation have demonstrated its utility as a prebiotic (4). Systematic review and meta-analyses of qualifying clinical trials have convincingly showed that oral supplementation of inulin or inulin-type fructans promotes prebiotic effects, such as increased fecal abundance of Bifidobacterium and Lactobacillus spp., improve blood lipid profiles, and improved mineral absorption (4,9). ...
Fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) have emerged as key contributors to digestive discomfort and intolerance to certain vegetables, fruits, and plant-based foods. Although strategies exist to minimize FODMAP consumption and exposure, exogenous enzyme supplementation targeting the fructan-type FODMAPs has been underexploited. The objective of this study was to test the hydrolytic efficacy of a food-grade, non-genetically engineered microbial inulinase preparation toward inulin-type fructans in the INFOGEST in vitro static simulation of gastrointestinal (GI) digestion. Purified inulin was shown to undergo acid-mediated hydrolysis at high gastric acidity as well as predominantly inulinase-mediated hydrolysis at lower gastric acidity. Inulinase dose-response simulations of inulin, garlic, and high-fructan meal digestion in the gastric phase suggest that as little as 50 inulinase units (INU) and up to 800 INU per serving promote fructan hydrolysis better than the control simulations without inulinase. Liquid chromatography-mass spectrometry (LC-MS) profiling of fructo-oligosaccharides (FOS) in the gastric digestas following inulinase treatment confirms the fructolytic activity of inulinase under simulated digestive conditions. Altogether, these in vitro digestion data support the use of microbial inulinase as an exogenous enzyme supplement for reducing dietary fructan-type FODMAP exposure.
... With the development of the concept of precision nutrition, researchers have begun to explore the possibility of microbiota-targeted foods. A meta-analysis involving 2225 subjects showed that inulin fructans could increase Bifidobacterium abundance in healthy people, increase the frequency of defecation in healthy adults, and reduce stool hardness in healthy children (Nagy et al., 2022). A study based on a mouse model of graft-versus-host disease demonstrated that galacto-oligosaccharides could improve the survival rate and relieve disease symptoms of the model mice to a certain extent by affecting the intestinal microbiota (Holmes et al., 2022). ...
The gut microbiome (GM) influences the availability of micronutrients in the gastrointestinal tract; however, our insights into how colonic fermentation of prebiotic fibers and lactose is modulated by the presence...
The systemic effects of gastrointestinal (GI) microbiota in health and during chronic diseases is increasingly recognised. Dietary strategies to modulate the GI microbiota during chronic diseases have demonstrated promise. While changes in dietary intake can rapidly change the GI microbiota, the impact of dietary changes during acute critical illness on the microbiota remain uncertain. Dietary fibre is metabolised by carbohydrate-active enzymes and, in health, can alter GI microbiota. The aim of this scoping review was to describe the effects of dietary fibre supplementation in health and disease states, specifically during critical illness. Randomised controlled trials and prospective cohort studies that include adults (> 18 years age) and reported changes to GI microbiota as one of the study outcomes using non-culture methods, were identified. Studies show dietary fibres have an impact on faecal microbiota in health and disease. The fibre, inulin, has a marked and specific effect on increasing the abundance of faecal Bifidobacteria. Short chain fatty acids produced by Bifidobacteria have been shown to be beneficial in other patient populations. Very few trials have evaluated the effect of dietary fibre on the GI microbiota during critical illness. More research is necessary to establish optimal fibre type, doses, duration of intervention in critical illness.
Inulin is a polysaccharide of fructose produced from various plant sources and has wide applications in food industries. The present work aims to perform multiple regression analysis for optimization of inulin yield generated from the roots of chicory. Chicory roots were used to extract the main compound inulin using water as the extractant. Multiple regression analysis was carried out by investigating 3 independent variables, Volume of solvent (15-75 mL), time of extraction (10-30 min), and temperature of extraction (30-90 C). From the analysis, a maximum inulin yield of 1.91% at optimum volume of solvent, extraction time and temperature of 50 mL, 20.5 min and 90 C, respectively. Hence, multiple regression analysis could be effectively used to maximize inulin yield from chicory roots.
Inulin, a naturally occurring polysaccharide and dietary fiber, has garnered growing interest due to its potential in enhancing gastrointestinal health. This book offers an in-depth study of the present status of research on inulin and its influence on gastrointestinal diseases. The book consolidates research findings to examine the possible therapeutic benefits of inulin on various gastrointestinal disorders, such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and constipation. The book discusses the mechanisms that explain the positive benefits of inulin on gastrointestinal health. It emphasizes inulin’s capacity to regulate the composition of gut microbiota, stimulate the growth of beneficial bacteria (such as Bifidobacteria), and increase the production of short-chain fatty acids. These physiological changes help to preserve the integrity of the gut barrier, regulate the immune system, and decrease inflammation in the gastrointestinal tract. Furthermore, the book discusses the various obstacles and issues related with inulin supplementation, such as individual variations in tolerance and the need for individualized treatments. The book additionally looks at current research endeavors focused on determining the ideal dosage, duration, and target demographics that may derive the greatest advantages from inulin supplementation. In summary, this book is a helpful resource for healthcare professionals, researchers, and consumers seeking to understand the current scientific evidence on the use of inulin as a viable treatment approach for different gastrointestinal conditions. It highlights the necessity for additional study to provide definitive guidelines for inulin supplementation and its incorporation into dietary recommendations for enhanced gastrointestinal health.
Obesity, a global epidemic, leads to metabolic dysregulation and systemic inflammation. Recently, therapies targeting the gut microbiome have garnered attention for metabolic health regulation. This study evaluates the potential of inulin‐coated medium‐chain triglyceride (InuMCT) microcapsules in rats with diet‐induced obesity (DIO). Inulin prebiotic fibers have been shown to promote the gut microbiome, while the digestion products of medium chain triglycerides (MCTs), free fatty acids, and mono‐/diglycerides, can attenuate pro‐inflammatory outcomes. It is hypothesized that encapsulating MCTs within inulin via spray drying creates a solid dosage form that can exert multifunctional effects in ameliorating inflammation in DIO. Inulin and InuMCT treatments not only reduce DIO weight gain but also improve metabolic markers in high‐fat diet (HFD) fed rats. Specifically, inulin attenuates the reduction of high‐density lipoprotein (HDL) by 55% and lowers glucose levels by 21%. Meanwhile, InuMCT increases HDL by 23% and reduces glucose levels by 15%. Furthermore, inulin decreases serum proinflammatory tumor necrosis factor‐alpha (TNF‐α) by 35%, while InuMCT further reduces TNF‐α to normal diet levels within 21 days. These results highlight InuMCT's superior efficacy, offering a promising strategy for combating obesity and related metabolic diseases.
Recently there is much debate in the scientific community over the impact of the food matrix on prebiotic efficacy of inulin-type fructans. Previous studies suggest that prebiotic selectivity of inulin-type fructans towards bifidobacteria is unaffected by the food matrix. Due to differences in study design, definitive conclusions cannot be drawn from these findings with any degree of certainty. In this randomised trial, we aimed to determine the effects that different food matrices had on the prebiotic efficacy of inulin-type fructans following a standardised 10-day, 4-arm, parallel, randomised protocol with inulin either in pure form or incorporated into shortbread biscuits, milk chocolate or a rice drink. Similar increases in Bifidobacterium counts were documented across all four interventions using both fluorescence in situ hybridisation (pure inulin: 0.63; shortbread: 0.59; milk chocolate: 0.65 and rice drink: 0.71 (log 10 cells/g wet faeces) and 16S rRNA sequencing quantitative microbiome profiling data (pure inulin: 1.21 × 10 ⁹ ; shortbread: 1.47 × 10 ⁹ ; milk chocolate: 8.59 × 10 ⁸ and rice drink: 1.04 × 10 ⁹ (cells/g wet faeces) (all ). From these results, we can confirm that irrespective of the food matrix, the selectivity of inulin-type fructans towards Bifidobacterium is unaffected, yet the compositional make-up of the food matrix may have implications regarding wider changes in the microbiota.
Background:
There is increasing interest in the bi-directional relationship existing between the gut and brain and the effects of both oligofructose and 2'fucosyllactose to alter microbial composition and mood state. Yet, much remains unknown about the ability of oligofructose and 2'fucosyllactose to improve mood state via targeted manipulation of the gut microbiota.
Objectives:
We aimed to compare the effects of oligofructose and 2'fucosyllactose alone and in combination against maltodextrin (comparator) on microbial composition and mood state in a working population.
Methods:
We conducted a 5-week, 4-arm, parallel, double-blind, randomised, placebo-controlled trial in 92 healthy adults with mild-to-moderate levels of anxiety and depression. Subjects were randomised to oligofructose 8 g/day (plus 2 g/day maltodextrin); maltodextrin 10 g/day; oligofructose 8 g/day plus 2'fucosyllactose (2 g/day) or 2'fucosyllactose 2 g/day plus (8 g/day maltodextrin). Changes in microbial load (FISH-FLOW) and composition (16s rRNA sequencing) were the primary outcomes. Secondary outcomes included gastrointestinal sensations, bowel habits and mood state parameters.
Results:
There were significant increases in several bacterial taxa including Bifidobacterium, Bacteroides, Roseburia and Faecalibacterium prausnitzii in both the oligofructose and oligofructose/2'fucosyllactose interventions (all P ≤ 0.05). Changes in bacterial taxa were highly heterogenous upon 2'fuscoyllactose supplementation. Significant improvements in Beck Depression Inventory, State Trait Anxiety Inventory Y1 and Y2, and Positive and Negative Affect Schedule scores and cortisol awakening response were detected across oligofructose, and 2'fucosyllactose and oligofructose/2'fucosyllactose combination interventions (all P ≤ 0.05). Both sole oligofructose and oligofructose/2'fuscosyllactose combination interventions outperformed both sole 2'fucosyllactose and maltodextrin in improvements in several mood state parameters (all P ≤ 0.05).
Conclusion:
The results of this study indicate that oligofructose and combination of oligofructose/2'fucosyllactose, can beneficially alter microbial composition along with improving mood state parameters. Future work is needed to understand key microbial differences separating individual responses to 2'fucosyllactose supplementation.
Trial registration:
ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT05212545): NCT05212545.
Inulin-type fructans (ITF), including short-chain fructooligosaccharides (scFOS), oligofructose, and inulin, are commonly used fibers that are widely regarded as prebiotic for their ability to be selectively utilized by the intestinal microbiota to confer a health benefit. However, the literature thus far lacks a thorough discussion of the evidence from human clinical trials for the prebiotic effect of ITF, including both effects on the intestinal microbiota composition as well as the intestinal and extraintestinal (e.g., glucose homeostasis, lipids, mineral absorption and bone health, appetite and satiety, inflammation and immune function, and body composition) benefits. Additionally, there is a lack of discussion regarding aspects such as the effect of ITF chain length on its intestinal and extraintestinal effects. The overall objective of this systematic review was to summarize the prebiotic potential of ITF based on the results of human clinical trials in healthy adult populations. Evidence from studies included in the current review suggest that ITF have a prebiotic effect on the intestinal microbiota, promoting the abundances of Bifidobacterium, Lactobacillus, and Faecalibacterium prausnitzii. Beneficial health effects reported following ITF intake include improved intestinal barrier function, improved laxation, increased insulin sensitivity, decreased triglycerides and an improved lipid profile, increased absorption of calcium and magnesium, and increased satiety. While there is some evidence for differing effects of ITF based on chain length, lack of direct comparisons and detailed descriptions of physicochemical properties limit the ability to draw conclusions from human clinical studies. Future research should focus on elucidating the mechanisms by which the intestinal microbiota mediates or modifies the effects of ITF on human health and the contribution of individual factors such as age and metabolic health to move towards personalization of prebiotic application.
Scope
During ageing, dysbiosis in the intestinal microbiota might occur and impact health. There is a paucity of studies on the effect of fiber on the elderly microbiota and the flexibility of the aged microbiota upon prebiotic intake. We hypothesized that chicory long‐chain inulin consumption can change microbiota composition, microbial fermentation products and immunity in the elderly.
Methods and results
A double‐blind, placebo‐controlled trial was performed in healthy individuals (55‐80 years), in which microbiota composition was studied before, during and after two months of chicory long‐chain inulin consumption. Fecal SCFA concentrations, T cell subsets and antibody responses against a Hepatitis B (HB) vaccine were measured as well. Inulin consumption modified the microbiota composition, as measured by 16S rRNA sequencing. Participants consuming inulin had a higher microbial diversity and a relative higher abundance of the Bifidobacterium genus, as well as Alistipes shahii, Anaerostipes hadrus, and Parabacteroides distasonis. While the immune responses remained unchanged, the isobutyric acid levels, an undesired fermentation product, tended to be lower in the inulin group.
Conclusions
Overall, we show for the first time that the gut microbiota composition is still sensitive to chicory long‐chain inulin induced changes in an ageing population, although this did not translate into an improved immune response to a HB vaccine.
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Gamma aminobutyric acid (GABA) is the principal inhibitory neurotransmitter playing a key role in anxiety and depression disorders in mammals. Recent studies revealed that members of the gut microbiota are able to produce GABA modulating the gut–brain axis response. Among members of the human gut microbiota, bifidobacteria are well known to establish many metabolic and physiologic interactions with the host. In this study, we performed genome analyses of more than 1,000 bifidobacterial strains publicly available revealing that Bifidobacterium adolescentis taxon might represent a model GABA producer in human gastrointestinal tract. Moreover, the in silico screening of human/animal metagenomic datasets showed an intriguing association/correlation between B. adolescentis load and mental disorders such as depression and anxiety. Interestingly, in vitro screening of 82 B. adolescentis strains allowed identifying two high GABA producers, i.e. B. adolescentis PRL2019 and B. adolescentis HD17T2H, which were employed in an in vivo trial in rats. Feeding Groningen rats with a supplementation of B. adolescentis strains, confirmed the ability of these microorganisms to stimulate the in vivo production of GABA highlighting their potential implication in gut–brain axis interactions.
PurposeCompared to a healthy population, the gut microbiota in type 2 diabetes presents with several unfavourable features that may impair glucose regulation. The aim of this study was to evaluate the prebiotic effect of inulin-type fructans on the faecal microbiota and short-chain fatty acids (SCFA) in patients with type 2 diabetes.Methods
The study was a placebo controlled crossover study, where 25 patients (15 men) aged 41–71 years consumed 16 g of inulin-type fructans (a mixture of oligofructose and inulin) and 16-g placebo (maltodextrin) for 6 weeks in randomised order. A 4-week washout separated the 6 weeks treatments. The faecal microbiota was analysed by high-throughput 16S rRNA amplicon sequencing and SCFA in faeces were analysed using vacuum distillation followed by gas chromatography.ResultsTreatment with inulin-type fructans induced moderate changes in the faecal microbiota composition (1.5%, p = 0.045). A bifidogenic effect was most prominent, with highest positive effect on operational taxonomic units (OTUs) of Bifidobacterium adolescentis, followed by OTUs of Bacteroides. Significantly higher faecal concentrations of total SCFA, acetic acid and propionic acid were detected after prebiotic consumption compared to placebo. The prebiotic fibre had no effects on the concentration of butyric acid or on the overall microbial diversity.Conclusion
Six weeks supplementation with inulin-type fructans had a significant bifidogenic effect and induced increased concentrations of faecal SCFA, without changing faecal microbial diversity. Our findings suggest a moderate potential of inulin-type fructans to improve gut microbiota composition and to increase microbial fermentation in type 2 diabetes.Trial registrationThe trial is registered at clinicaltrials.gov (NCT02569684).
Background
Higher protein intakes may help reduce sarcopenia and facilitate recovery from illness and injury in older adults. However, high-protein diets (HPDs) including animal-sourced foods may negatively perturb the microbiota, and provision of probiotics and prebiotics may mitigate these effects.
Objective
The aim of this study was to examine the effects of HPD, with and without a probiotic and/or prebiotic, on gut microbiota and wellness in older women.
Design
We conducted an 18-week, double-blind, placebo-controlled, crossover study.
Participants/setting
Participants were healthy, older women (mean age±standard deviation=73.7±5.6 years; n=26) recruited from Florida.
Intervention
Participants received a weight-maintenance HPD for 2-week periods and the following, in random order: HPD alone (1.5 to 2.2 g/kg/day protein); HPD plus multistrain probiotic formulation (1.54×10⁹Bifidobacterium bifidum HA-132, 4.62×10⁹Bifidobacterium breve HA-129, 4.62×10⁹Bifidobacterium longum HA-135, 4.62×10⁹Lactobacillus acidophilus HA-122, and 4.62×10⁹Lactobacillus plantarum HA-119), HPD plus prebiotic (5.6 g inulin), and HPD plus synbiotic (probiotic plus inulin), separated by 2-week washouts. Stools were collected per period for quantitative polymerase chain reaction (strain recovery) and 16S ribosomal RNA gene amplicon sequencing analyses (microbiota profile). Measures of gastrointestinal and general wellness were assessed.
Main outcome measures
Microbiota composition and probiotic strain recovery were measured.
Statistical analyses
Microbiota composition was analyzed by Wilcoxon signed-rank test and t test. Secondary outcomes were analyzing using generalized linear mixed models.
Results
The microbiota profile demonstrated relative stability with the HPD; representation of Lactobacillus, Lactococcus, and Streptococcus were enhanced, whereas butyrate producers, Roseburia and Anaerostipes, were suppressed. Lactococcus was suppressed with synbiotic vs other HPD periods. Recovery was confirmed for all probiotic strains. Indicators of wellness were unchanged, with the exception of a minimal increase in gastrointestinal distress with inulin. Fat-free mass increased from baseline to study end.
Conclusions
An HPD adhering to the recommended acceptable macronutrient distribution ranges maintains wellness in healthy older women and exerts minor perturbations to the microbiome profile, a group that may benefit from a higher protein intake. ClinicalTrials.gov ID: NCT #02445560.
The human gut is inhabited by trillions of microorganisms composing a dynamic ecosystem implicated in health and disease. The composition of the gut microbiota is unique to each individual and tends to remain relatively stable throughout life, yet daily transient fluctuations are observed. Diet is a key modifiable factor influencing the composition of the gut microbiota, indicating the potential for therapeutic dietary strategies to manipulate microbial diversity, composition, and stability. While diet can induce a shift in the gut microbiota, these changes appear to be temporary. Whether prolonged dietary changes can induce permanent alterations in the gut microbiota is unknown, mainly due to a lack of long-term human dietary interventions, or long-term follow-ups of short-term dietary interventions. It is possible that habitual diets have a greater influence on the gut microbiota than acute dietary strategies. This review presents the current knowledge around the response of the gut microbiota to short-term and long-term dietary interventions and identifies major factors that contribute to microbiota response to diet. Overall, further research on long-term diets that include health and microbiome measures is required before clinical recommendations can be made for dietary modulation of the gut microbiota for health.
Background
Inulin, consisting of repetitive fructosyl units linked by β(2,1) bonds, is a readily fermentable fiber by intestinal bacteria that generates large quantities of short-chain fatty acids (SCFA). In individuals with constipation, it was reported that inulin ingestion was associated with a significant increase in stool frequency, suggesting a potential impact of inulin on human gut microbiota composition. Progress in high-throughput technologies allow assessment of human-associated microbiomes in terms of diversity and taxonomic or functional composition, and can identify changes in response to a specific supplementation. Hence, to understand the effects of inulin on the human gut microbiome is pivotal to gain insight into their mechanisms of action.
Methods
Here, we conducted a systematic review of human studies in adult individuals showing the effects of inulin on the gut microbiome. We searched in MEDLINE, EMBASE, Web of Science, and Scopus databases for articles in English published in peer-reviewed journals and indexed up until March 2019. We used multiple search terms capturing gut microbiome, gut microflora, intestinal microbiota, intestinal flora, gut microbiota, gut flora, microbial gut community, gut microbial composition, and inulin.
Results
Overall, nine original articles reported the effects of inulin on microbiome composition in adult humans, most of them being randomized, double-blind, placebo-controlled trials (n = 7). Studies varied significantly in design (3 studies associated inulin and oligofructose), supplementation protocols (from 5 to 20 gr per day of inulin consumed) and in microbiome assessment methods (16S sequencing, n = 7). The most consistent change was an increase in Bifidobacterium. Other concordant results included an increase in relative abundance of Anaerostipes, Faecalibacterium, and Lactobacillus, and a decrease in relative abundance of Bacteroides after inulin supplementation.
Conclusions
Our systematic review assessed the evidence for the effects of inulin supplementation on the human gut microbiome. However, these in vivo studies did not confirm in vitro experiments as the taxonomic alterations were not associated with increase in short-chain fatty acids levels.
The revised edition of the Handbook offers the only guide on how to conduct, report and maintain a Cochrane Review.
The second edition of The Cochrane Handbook for Systematic Reviews of Interventions contains essential guidance for preparing and maintaining Cochrane Reviews of the effects of health interventions. Designed to be an accessible resource, the Handbook will also be of interest to anyone undertaking systematic reviews of interventions outside Cochrane, and many of the principles and methods presented are appropriate for systematic reviews addressing research questions other than effects of interventions.
This fully updated edition contains extensive new material on systematic review methods addressing a wide-range of topics including network meta-analysis, equity, complex interventions, narrative synthesis, and automation. Also new to this edition, integrated throughout the Handbook, is the set of standards Cochrane expects its reviews to meet.
Written for review authors, editors, trainers and others with an interest in Cochrane Reviews, the second edition of The Cochrane Handbook for Systematic Reviews of Interventions continues to offer an invaluable resource for understanding the role of systematic reviews, critically appraising health research studies and conducting reviews.
Background:
Insulin resistance (IR) is a physiological condition related to type 2 diabetes mellitus (T2DM) and obesity, which is associated with high blood insulin and glucose. Inulin-type carbohydrate (ITC) is a kind of fermentable fructan that can reduce glucose and ameliorate IR in an animal model, but the effect in clinical trials is controversial.
Objective:
The authors conducted a systematic literature review to evaluate the effect of ITC supplementation in ameliorating IR in T2DM and obese patients.
Methods:
Multiple databases were queried for studies before December 25, 2018, which involved supplementation with ITC in ameliorating IR in T2DM and obese patients. Studies that involved meta-analysis of the body mass index (BMI), fasting plasma glucose (FPG), fasting insulin (FI), HbA1c, homeostatic model assessment IR (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) of T2DM subjects were included. HOMA-IR and QUICKI were identified as the primary outcomes. A systematic review was performed to evaluate the effect of ITC on IR in obese patients.
Results:
The database search yielded 25 studies, which met the inclusion criteria; 11 articles were meta-analyzed, and 5 other articles on T2DM and 9 articles on simple obesity were systematically reviewed. Our results did not find ITC supplementation decrease postintervention and reduction data of BMI (P = 0.08). However, it can significantly decrease postintervention and reduction data of FPG, FI, HbA1c, and HOMA-IR. Heterogeneity was eliminated by subgroup analysis according to baseline BMI. There was no significant difference in the amelioration of QUICKI between the ITC and control groups. However, the difference was statistically significant and the heterogeneity was eliminated after subgroup analysis according to intakes of ITC. 14 articles for a systematic review found that the results of blood glucose, insulin, and HbA1c were controversial. Only one of the seven studies on simple obesity concluded that ITC intervention significantly ameliorated HOMA-IR, while the other six did not.
Conclusion:
Supplementation of ITC can ameliorate IR in T2DM, especially in obese T2DM patients, but the effects are controversial in obese patients.
Background:
Soluble fibre modulates airway inflammation in animal models. The aim of this study was to investigate the effects of soluble fibre supplementation, with and without a probiotic, on plasma short chain fatty acids (SCFA), airway inflammation, asthma control and gut microbiome in adults with asthma.
Methods:
A randomised, double-blinded, placebo controlled 3-way cross-over trial in 17 subjects with stable asthma at the Hunter Medical Research Institute, Newcastle, Australia. Subjects received 3 × 7 day oral interventions in random order; soluble fibre (inulin 12 g/day), soluble fibre + probiotic (inulin 12 g/day + multi-strain probiotic >25 billion CFU) and placebo. Plasma SCFA, sputum cell counts and inflammatory gene expression, asthma control gut microbiota, adverse events including gastrointestinal symptoms were measured.
Findings:
There was no difference in change in total plasma SCFA levels (μmol/L) in the placebo versus soluble fibre (Δmedian [95% CI] 16·3 [-16·9, 49·5], p = 0·335) or soluble fibre+probiotic (18·7 [-14·5, 51·9], p = 0·325) group. Following the soluble fibre intervention there was an improvement in the asthma control questionnaire (ACQ6) (∆median (IQR) -0·35 (-0·5, -0·13), p = 0·006), sputum %eosinophils decreased (-1.0 (-2·5, 0), p = 0·006) and sputum histone deacetylase 9 (HDAC9) gene expression decreased (-0.49 (-0.83, -0.27) 2-ΔCt, p = .008). Individual bacterial operational taxonomic units changed following both inulin and inulin+probiotic arms.
Interpretation:
Soluble fibre supplementation for 7 days in adults with asthma did not change SCFA levels. Within group analysis showed improvements in airway inflammation, asthma control and gut microbiome composition following inulin supplementation and these changes warrant further investigation, in order to evaluate the potential of soluble fibre as a non-pharmacological addition to asthma management. FUND: John Hunter Hospital Charitable Trust.
Objective
To investigate the underlying mechanisms behind changes in glucose homeostasis with delivery of propionate to the human colon by comprehensive and coordinated analysis of gut bacterial composition, plasma metabolome and immune responses.
Design
Twelve non-diabetic adults with overweight and obesity received 20 g/day of inulin-propionate ester (IPE), designed to selectively deliver propionate to the colon, a high-fermentable fibre control (inulin) and a low-fermentable fibre control (cellulose) in a randomised, double-blind, placebo-controlled, cross-over design. Outcome measurements of metabolic responses, inflammatory markers and gut bacterial composition were analysed at the end of each 42-day supplementation period.
Results
Both IPE and inulin supplementation improved insulin resistance compared with cellulose supplementation, measured by homeostatic model assessment 2 (mean±SEM 1.23±0.17 IPE vs 1.59±0.17 cellulose, p=0.001; 1.17±0.15 inulin vs 1.59±0.17 cellulose, p=0.009), with no differences between IPE and inulin (p=0.272). Fasting insulin was only associated positively with plasma tyrosine and negatively with plasma glycine following inulin supplementation. IPE supplementation decreased proinflammatory interleukin-8 levels compared with cellulose, while inulin had no impact on the systemic inflammatory markers studied. Inulin promoted changes in gut bacterial populations at the class level (increased Actinobacteria and decreased Clostridia) and order level (decreased Clostridiales) compared with cellulose, with small differences at the species level observed between IPE and cellulose.
Conclusion
These data demonstrate a distinctive physiological impact of raising colonic propionate delivery in humans, as improvements in insulin sensitivity promoted by IPE and inulin were accompanied with different effects on the plasma metabolome, gut bacterial populations and markers of systemic inflammation.
Background and Objective
Current studies give us inconsistent results regarding the inulin consumption in cancer patients. The results of to-date studies are summarized in this systematic review.
Methods
Web of Science (Science citation index expanded), PubMed (Medline), Embase and CENTRAL Science direct, Google scholar, Scopus and Cochrane were searched. Cochrane Collaboration’s ‘Risk of Bias’ tool was used to assess the quality of included articles.
Results
Our search yielded 2652 studies after the elimination of duplicates. Three randomized controlled trials (RCTs), reporting results from 197 patients, were eligible for inclusion in the present systematic review. Risk of bias in these studies was assessed as high and moderate.
Conclusion
The available evidence is inconclusive regarding the effect of inulin and oligofructose on cancer outcomes. Nonetheless, possible inulin positive effects including improved stool consistency after abdomen radiotherapy and increased stool butyrate content which is involved in controlling tumor cells proliferation and apoptosis should not be denied. Further research is needed in this area before strong conclusions can be drawn.
Supplementing kindergarten children during a cold season with a prebiotic inulin-type fructans product with shorter and longer fructan chains has been shown to reduce febrile episodes requiring medical attention and to lower the incidence of sinusitis. These beneficial effects may be connected to the specific modulation of children’s gut microbiota. By applying quantitative and qualitative microbiota analysis this study aimed at characterising the gut microbiota composition and at exploring effects of prebiotic intervention on the gut microbiota during a 24-weeks intervention and during antibiotic treatment in healthy children. The study was a randomised, placebo-controlled trial with 258 healthy children aged 3 to 6 years consuming 6 g/day prebiotic inulin-type fructans or maltodextrin. During the course of the study, faecal samples were collected and subject to targeted qPCR analysis and phylogenetic profiling by multiplexed high throughput sequencing of the prokaryotic 16S rRNA gene PCR amplicons. The microbiota composition of the cohort could be clustered into three distinct constellations (enterotypes). Prebiotic intake resulted in a selective modulation of the gut microbiota composition. Relative abundance of Bifidobacterium was significantly higher in the prebiotic group (n=104) compared to control group (n=105) and this effect was found for all three enterotypes. Antibiotic administration decreased the relative abundance of Bifidobacterium in both groups. Nonetheless, children of the prebiotic group receiving antibiotic treatment displayed significantly higher levels of Bifidobacterium than children receiving the placebo control. Prebiotic supplementation induced specific changes in the gut microbiota composition of children aged 3 to 6 years. Moreover, it attenuated antibiotic-induced disturbances in the gut microbiota composition as shown by higher relative abundance of bifidobacteria at the end of the antibiotic treatment in the prebiotic group. With the previously reported benefits on immune function, the study contributes to the evidence on the immune-modulating effects of prebiotics through gut microbiota modifications. The study was registered as NCT03241355 (https://clinicaltrials.gov/show/NCT03241355).
Constipation often begins in the first year of life. The aim of this study was to assess the effect of fructooligosaccharides (FOS) in the treatment of infants with constipation. This randomized, double-blind, placebo-controlled clinical trial included infants with constipation who were randomly assigned to one of two parallel groups: FOS or placebo. Either the FOS supplement or the placebo was added to the infant formula. Thirty-six infants completed the 4-week intervention. Therapeutic success occurred in 83.3% of the FOS group infants and in 55.6% of the control group infants (p = 0.073; one-tailed test). Compared with the control group, the FOS group exhibited a higher frequency of softer stools (p = 0.035) and fewer episodes of straining and/or difficulty passing stools (p = 0.041). At the end of the intervention, the mouth-to-anus transit time was shorter (22.4 and 24.5 h, p = 0.035), and the Bifidobacterium sp. count was higher (p = 0.006) in the FOS group. In conclusion, the use of FOS in infants with constipation was associated with significant improvement in symptoms, but the results showed no statistical significance regarding the success of the therapy compared with the control group. FOS was associated with reduced bowel transit time and higher counts of the genus Bifidobacterium in the stool.
Studies of probiotics, fructan-type prebiotics, and synbiotics in patients with ulcerative colitis (UC) show significant heterogeneity in methodology and results. Here, we study the efficacy of such interventions and the reasons for the heterogeneity of their results. Eligible random controlled trials were collected from the PUBMED and SCOPUS databases. A total of 18 placebo-controlled and active treatment-controlled (i.e., mesalazine) studies were selected with a Jadad score ≥ 3, including 1491 patients with UC. Data for prebiotics and synbiotics were sparse and consequently these studies were excluded from the meta-analysis. The UC remission efficacy of probiotics was measured in terms of relative risk (RR) and odds ratio (OR). Significant effects were observed in patients with active UC whenever probiotics containing bifidobacteria were used, or when adopting the US Food and Drug Administration (FDA)-recommended scales (UC Disease Activity Index and Disease Activity Index). By the FDA recommended scales, the RR was 1.55 (CI95%: 1.13–2.15, p-value = 0.007, I2 = 29%); for bifidobacteria-containing probiotics, the RR was 1.73 (CI95%: 1.23–2.43, p-value = 0.002, I2 = 35%). No significant effects were observed on the maintenance of remission for placebo-controlled or mesalazine-controlled studies. We conclude that a validated scale is necessary to determine the state of patients with UC. However, probiotics containing bifidobacteria are promising for the treatment of active UC.
Production of short-chain fatty acids (SCFAs), especially butyrate, in the gut microbiome is required for optimal health but is frequently limited by the lack of fermentable fiber in the diet. We attempted to increase butyrate production by supplementing the diets of 174 healthy young adults for 2 weeks with resistant starch from potatoes (RPS), resistant starch from maize (RMS), inulin from chicory root, or an accessible corn starch control. RPS resulted in the greatest increase in total SCFAs, including butyrate. Although the majority of microbiomes responded to RPS with increases in the relative abundance of bifidobacteria, those that responded with an increase in Ruminococcus bromii or Clostridium chartatabidum were more likely to yield higher butyrate concentrations, especially when their microbiota were replete with populations of the butyrate-producing species Eubacterium rectale . RMS and inulin induced different changes in fecal communities, but they did not generate significant increases in fecal butyrate levels.
IMPORTANCE These results reveal that not all fermentable fibers are equally capable of stimulating SCFA production, and they highlight the importance of the composition of an individual’s microbiota in determining whether or not they respond to a specific dietary supplement. In particular, R. bromii or C. chartatabidum may be required for enhanced butyrate production in response to RS. Bifidobacteria, though proficient at degrading RS and inulin, may not contribute to the butyrogenic effect of those fermentable fibers in the short term.
Purpose
The aim of this study was to identify the minimally meaningful dosage of inulin leading to a prebiotic effect in Indonesian infants.
Methods
In a randomized controlled double-blinded, parallel, 3-arm intervention study, 164 healthy formula-fed infants aged 3 to 5 months first obtained formula-A (without inulin) during a 4-week adaptation period. Subsequently, 142 subjects were subjected to a 4-week feeding period by administering either formula-A (no inulin), formula-B (0.2 g/100 mL inulin) or formula-C (0.4 g/100 mL inulin). The primary outcome parameter was %-bifidobacteria in faecal samples determined using quantitative polymerase chain reaction analyses. Secondary outcome parameters were faecal %-lactobacilli, pH and stool frequency, and consistency. Growth and tolerance/adverse effects were recorded as safety parameters.
Results
Typical %-bifidobacteria and %-lactobacilli at the end of the adaptation period in the study population were 14% and 2%, respectively. For faecal pH, significant differences between formula groups A vs. C and A vs. B were found at the end of the intervention period. Testing for differences in faecal %-bifidobacteria and %-lactobacilli between groups was hampered by non-normal data set distributions; no statistically significant differences were obtained. Comparisons within groups revealed that only in formula group C, all the three relevant parameters exhibited a significant effect with an increase in faecal %-bifidobacteria and %-lactobacilli and a decrease in pH.
Conclusion
A consistent prebiotic effect along with a decrease in pH and increase in %-bifidobacteria and %-lactobacilli was found only in the group administered 0.4 g inulin/100 mL.
The aim of this systematic review and meta-analysis was to assess the effects of β-fructan supplementation on bowel function in healthy volunteers and patients. The search process was based on the selection of publications listed in the Pubmed and EUPMC database until December 2017, plus two unpublished studies, to identify studies evaluating the impact of β-fructans on bowel movement and stool parameters. Forty-seven publications were selected for inclusion. Primary parameter was frequency of bowel movements, evaluated by the number of defecations per day during the study period. Secondary outcomes were stool consistency, stool dry and wet weights, and transit time. Short-chain (DP < 10) β-fructans contributed to increased stool frequency (0.36 defecation +/− 0.06 per day; p < 0.001), while no significant effect was reported with long-chain (DP ≥ 10) β-fructans (−0.03 +/− 0.11, p = 0.82). A minimal increase in stool wet weight was also statistically demonstrated with short-chain β-fructans. Moreover, the meta-analysis highlighted significant differences in stool consistency in contrast to fecal dry weight after β-fructan supplementation. This systematic review and meta-analysis indicates that short-chain β-fructan supplementation has a positive effect on bowel function by significantly increasing the frequency of bowel movements.
Background & aims
Ingestion of poorly digested, fermentable carbohydrates (fermentable oligo-, di-, mono-saccharides and polyols; FODMAPs) have been implicated in exacerbating intestinal symptoms and the reduction of intake with symptom alleviation. Restricting FODMAP intake is believed to relieve colonic distension by reducing colonic fermentation but this has not been previously directly assessed. We performed a randomised controlled trial comparing the effect of a low FODMAP diet combined with either maltodextrin or oligofructose on colonic contents, metabolites and microbiota.
Methods
A parallel randomised controlled trial in healthy adults (n = 37). All subjects followed a low FODMAP diet for a week and supplemented their diet with either maltodextrin (MD) or oligofructose (OF) 7g twice daily. Fasted assessments performed pre- and post-diet included MRI to assess colonic volume, breath testing for hydrogen and methane, and stool collection for microbiota analysis.
Results
The low FODMAP diet was associated with a reduction in Bifidobacterium and breath hydrogen, which was reversed by oligofructose supplementation. The difference in breath hydrogen between groups post-intervention was 27ppm (95% CI 7 to 50, P<0.01). Colonic volume increased significantly from baseline in both groups (OF increased 110ml (19.6%), 95% CI 30ml to 190ml, P = 0.01; MD increased 90ml (15.5%), 95% CI 6ml to 175ml, P = 0.04) with no significant difference between them. Colonic volumes correlated with total breath hydrogen + methane. A divergence in Clostridiales abundance was observed with increased abundance of Ruminococcaceae in the maltodextrin group, while in the oligofructose group, Lachnospiraceae decreased. Subjects in either group with high methane production also tended to have high microbial diversity, high colonic volume and greater abundance of methanogens.
Conclusion
A low FODMAP diet reduces total bacterial count and gas production with little effect on colonic volume.
Background:
Inulin-type fructans used in formula have been shown to promote microbiota composition and stool consistency closer to those of breastfed infants and to have beneficial effects on fever occurrence, diarrhea, and incidence of infections requiring antibiotic treatment in infants.
Objectives:
The primary study aim was to explore whether prophylactic supplementation with prebiotic fructans is able to influence the frequency of infectious diseases in kindergarten children during a winter period. A secondary objective was to ascertain the effect on the intestinal microbiota.
Methods:
142 boys and 128 girls aged 3-6 y were randomly allocated to consume 6 g/d fructans or maltodextrin for 24 wk. At baseline, stool samples were collected for microbiota analysis and anthropometric measurements were made. During the intervention period diagnoses were recorded by physicians, whereas disease symptoms, kindergarten absenteeism, dietary habits, and stool consistency were recorded by parents. Baseline measurements were repeated at wk 24.
Results:
In total 219 children finished the study. Both the relative abundance of Bifidobacterium (P < 0.001) and that of Lactobacillus (P = 0.014) were 19.9% and 7.8% higher, respectively, post data normalization, in stool samples of children receiving fructans as compared with those of controls at wk 24. This was accompanied by significantly softer stools within the normal range in the prebiotic group from wk 12 onwards. The incidence of febrile episodes requiring medical attention [0.65 ± 1.09 compared with 0.9 ± 1.11 infections/(24 wk × child), P = 0.04] and that of sinusitis (0.01 ± 0.1 compared with 0.06 ± 0.25, P = 0.03) were significantly lower in the prebiotic group. The number of infectious episodes and their duration reported by parents did not differ significantly between the 2 intervention groups.
Conclusions:
Prebiotic supplementation modified the composition of the intestinal microbiota and resulted in softer stools in kindergarten-aged children. The reduction in febrile episodes requiring medical attention supports the concept of further studies on prebiotics in young children. This trial was registered at clinicaltrials.gov as NCT03241355.
Purpose:
In obesity and diabetes the liver is highly susceptible to abnormal uptake and storage of fat. In certain individuals hepatic steatosis predisposes to the development of non-alcoholic steatohepatitis (NASH), a disease marked by hepatic inflammation and fibrosis. Although the precise pathophysiology of NASH is unknown, it is believed that the gut microbiota-liver axis influences the development of this disease. With few treatment strategies available for NASH, exploration of gut microbiota-targeted interventions is warranted. We investigated the therapeutic potential of a prebiotic supplement to improve histological parameters of NASH.
Methods:
In a placebo-controlled, randomized pilot trial, 14 individuals with liver-biopsy-confirmed NASH [non-alcoholic fatty liver activity score (NAS) ≥ 5] were randomized to receive oligofructose (8 g/day for 12 weeks followed by 16 g/day for 24 weeks) or isocaloric placebo for 9 months. The primary outcome measure was the change in liver biopsy NAS score and the secondary outcomes included changes in body weight, body composition, glucose tolerance, inflammatory markers, and gut microbiota.
Results:
Independent of weight loss, oligofructose improved liver steatosis relative to placebo and improved overall NAS score (P = 0.016). Bifidobacterium was enhanced by oligofructose, whereas bacteria within Clostridium cluster XI and I were reduced with oligofructose (P < 0.05). There were no adverse side effects that deterred individuals from consuming oligofructose for treatment of this disease.
Conclusions:
Independent of other lifestyle changes, prebiotic supplementation reduced histologically-confirmed steatosis in patients with NASH. Larger follow-up studies are warranted.
Clinical trial:
This trial was registered at Clinicaltrials.com as NCT03184376.
Background:
Dysfunction of the gut microbiota is frequently reported as a manifestation of chronic diseases, and therefore presents as a modifiable risk factor in their development. Diet is a major regulator of the gut microbiota and certain types of dietary fiber may modify bacterial numbers and metabolism, including short-chain fatty acid (SCFA) generation.
Objective:
A systematic review and meta-analysis were undertaken to assess the effect of dietary fiber interventions on gut microbiota composition in healthy adults.
Design:
A systematic search was conducted across MEDLINE, EMBASE, CENTRAL, and CINAHL for randomized controlled trials using culture and/or molecular microbiological techniques evaluating the effect of fiber intervention on gut microbiota composition in healthy adults. Meta-analyses via a random-effects model were performed on alpha diversity, prespecified bacterial abundances including Bifidobacterium and Lactobacillus spp., and fecal SCFA concentrations comparing dietary fiber interventions with placebo/low-fiber comparators.
Results:
A total of 64 studies involving 2099 participants were included. Dietary fiber intervention resulted in higher abundance of Bifidobacterium spp. [standardized mean difference (SMD) 0.64 (95% CI: 0.42, 0.86); P < 0.00001)] and Lactobacillus spp. [SMD: 0.22 (0.03, 0.41), P = 0.02] as well as fecal butyrate concentration [SMD: 0.24 (0.00, 0.47), P = 0.05] compared with placebo/low-fiber comparators. Subgroup analysis revealed that fructans and galacto-oligosaccharides led to significantly greater abundance of both Bifidobacterium spp. and Lactobacillus spp. compared with comparators (P < 0.00001 and P = 0.002, respectively). No differences in effect were found between fiber intervention and comparators for α-diversity, abundances of other prespecified bacteria, or other SCFA concentrations.
Conclusions:
Dietary fiber intervention, particularly involving fructans and galacto-oligosaccharides, leads to higher fecal abundance of Bifidobacterium and Lactobacillus spp. but does not affect α-diversity. Further research is required to better understand the role of individual fiber types on the growth of microbes and the overall gut microbial community. This review was registered at PROSPERO as CRD42016053101.
Celiac disease (CD) is associated with intestinal microbiota alterations. The administration of prebiotics could be a promising method of restoring gut homeostasis in CD. The aim of this study was to evaluate the effect of prolonged oligofructose-enriched inulin (Synergy 1) administration on the characteristics and metabolism of intestinal microbiota in CD children following a gluten-free diet (GFD). Thirty-four paediatric CD patients (mean age 10 years; 62% females) on a GFD were randomized into two experimental groups receiving Synergy 1 (10 g/day) or placebo (maltodextrin; 7 g/day) for 3 months. The quantitative gut microbiota characteristics and short-chain fatty acids (SCFAs) concentration were analysed. In addition, side effects were monitored. Generally, the administration of Synergy 1 in a GFD did not cause any side effects. After the intervention period, Bifidobacterium count increased significantly (p < 0.05) in the Synergy 1 group. Moreover, an increase in faecal acetate and butyrate levels was observed in the prebiotic group. Consequently, total SCFA levels were 31% higher than at the baseline. The presented trial shows that Synergy 1 applied as a supplement of a GFD had a moderate effect on the qualitative characteristics of faecal microbiota, whereas it stimulated the bacterial metabolite production in CD children.
Background
A lifelong gluten-free diet (GFD) is regarded as the only proven and accepted therapy for coeliac disease (CD). However, even patients who strictly follow a GFD often suffer from intestinal symptoms and malabsorption. Selective modulation of intestinal microbiota with prebiotics could remedy various symptoms associated with CD. The use of prebiotics in the treatment of intestinal diseases remains insufficiently investigated. To our knowledge, this study makes the first attempt to evaluate the effect of prebiotic supplementation on gastrointestinal symptoms and nutritional status of children with CD. We hypothesized that adherence to a GFD supplemented with oligofructose-enriched inulin (Synergy 1) would deliver health benefits to children suffering from CD without any side effects, and that it would alleviate intestinal inflammation, restore and stabilize gut microbial balance and reverse nutritional deficiencies through enhanced absorption of vitamins and minerals.
Methods
A randomized, placebo-controlled clinical trial was designed to assess the impact of the Synergy 1 on paediatric CD patients following a GFD. We randomized 34 children diagnosed with CD into an intervention group receiving 10 g of the Synergy 1 supplement daily and a placebo group (receiving maltodextrin) during a 12-week nutritional intervention. Selected biochemical parameters, nutritional status and the characteristics of faecal bacteria will be determined in samples collected before and after the intervention. Analysis of vitamins and amino acids concentration in biological fluids will allow to assess the dietary intake of crucial nutrients. The compliance to a GFD will be confirmed by a Food Frequency Questionnaire (FFQ-6) and the analysis of serum anti-tissue transglutaminase and faecal gluten immunogenic peptides (GIP).
Conclusion
The identification of the beneficial effects of the Synergy 1 supplement on children with CD could have important implications for nutritional recommendations for CD patients and for alleviating the harmful effects of the disease.
Trial registration
ClinicalTrials.gov Registration Number: NCT03064997.
Electronic supplementary material
The online version of this article (doi:10.1186/s12937-017-0268-z) contains supplementary material, which is available to authorized users.
Bifidobacteria and Their Health-Promoting Effects, Page 1 of 2
Abstract
Bifidobacteria are members of the intestinal microbiota of mammals and other animals, and some strains are able to exert health-promoting effects. The genus Bifidobacterium belongs to the Actinobacteria phylum. Firmicutes, Bacteroidetes, and Actinobacteria constitute the most abundant phyla in the human intestinal microbiota, Firmicutes and Bacteroidetes being predominant in adults, and Actinobacteria in breast-fed infants, where bifidobacteria can reach levels higher than 90% of the total bacterial population. They are among the first microbial colonizers of the intestines of newborns, and play key roles in the development of their physiology, including maturation of the immune system and use of dietary components. Indeed, some nutrients, such as human milk oligosaccharides, are important drivers of bifidobacterial development. Some Bifidobacterium strains are considered probiotic microorganisms because of their beneficial effects, and they have been included as bioactive ingredients in functional foods, mainly dairy products, as well as in food supplements and pharma products, alone, or together with, other microbes or microbial substrates. Well-documented scientific evidence of their activities is currently available for bifidobacteria-containing preparations in some intestinal and extraintestinal pathologies. In this review, we focus on the role of bifidobacteria as members of the human intestinal microbiota and their use as probiotics in the prevention and treatment of disease.
Background & aims:
It might be possible to manipulate the intestinal microbiota with prebiotics or other agents to prevent or treat obesity. However, little is known about the ability of prebiotics to specifically modify gut microbiota in children with overweight/obesity or reduce body weight. We performed a randomized controlled trial to study the effects of prebiotics on body composition, markers of inflammation, bile acids in fecal samples, and composition of the intestinal microbiota in children with overweight or obesity.
Methods:
We performed a single-center, double-blind, placebo-controlled trial of 2 separate cohorts (March 2014 and August 2014) at the University of Calgary in Canada. Participants included children, 7-12 years old, with overweight or obesity (>85th percentile of body mass index) but otherwise healthy. Participants were randomly assigned to groups given either oligofructose-enriched inulin (OI; 8 g/day; n=22) or maltodextrin placebo (isocaloric dose, controls; n=20) once daily for 16 weeks. Fat mass and lean mass were measured using dual-energy-x-ray absorptiometry. Height, weight, and waist circumference were measured at baseline and every 4 weeks thereafter. Blood samples were collected at baseline and 16 weeks, and analyzed for lipids, cytokines, lipopolysaccharide, and insulin. Fecal samples were collected at baseline and 16 weeks; bile acids were profiled using high-performance liquid chromatography and the composition of the microbiota was analyzed by 16S rRNA sequencing and quantitative polymerase chain reaction. The primary outcome was change in percent body fat from baseline to 16 weeks.
Results:
After 16 weeks, children who consumed OI had significant decreases in body weight z-score (decrease of 3.1%), percent body fat (decrease of 2.4%), and percent trunk fat (decrease of 3.8%) compared with children given placebo (increase of 0.5%, increase of 0.05%, and decrease of 0.3%, respectively). Children who consumed OI also had a significant reduction in level of interleukin 6 from baseline (decrease of 15%) compared with the placebo group (increase of 25%). There was a significant decrease in serum triglycerides (decrease of 19%) in the OI group. Quantitative polymerase chain reaction showed a significant increase in Bifidobacterium spp. in the OI group compared with controls. 16S rRNA sequencing revealed significant increases in species of the genus Bifidobacterium and decreases in Bacteroides vulgatus within the group who consumed OI. In fecal samples, levels of primary bile acids increased in the placebo group but not in the OI group over the 16-week study period.
Conclusions:
In a placebo-controlled, randomized trial, we found a prebiotic (OI) to selectively alter the intestinal microbiota and significantly reduce body weight z-score, percent body fat, percent trunk fat, and serum level of interleukin 6 in children with overweight or obesity (Clinicaltrials.gov no: NCT02125955).
Almost half the cells and 1% of the unique genes found in our bodies are human, the rest are from microbes; predominantly bacteria, archaea, fungi, and viruses. These microorganisms collectively form the human microbiota, with most colonizing the gut. Recent technological advances, open access data-libraries, and application of high throughput sequencing have allowed these microbes to be identified and their contribution to neurological health examined. Emerging evidence links perturbations in the gut microbiota to neurological disease, including disease risk, activity, and progression. This review provides an overview of the recent advances in microbiome research in relation to neuro(auto)immune and neurodegenerative conditions affecting humans such as multiple sclerosis, neuromyelitis optica spectrum disorders, Parkinson's, Alzheimer's, Huntington's, and amyotrophic lateral sclerosis. Study design and terminology used in this rapidly evolving, highly multi-disciplinary field are summarized to empower and engage the neurology community in this 'newly discovered organ.' This article is protected by copyright. All rights reserved.
Objective
Contrary to the long-standing prerequisite of inducing selective (ie, bifidogenic) effects, recent findings suggest that prebiotic interventions lead to ecosystem-wide microbiota shifts. Yet, a comprehensive characterisation of this process is still lacking. Here, we apply 16S rDNA microbiota profiling and matching (gas chromatography mass spectrometry) metabolomics to assess the consequences of inulin fermentation both on the composition of the colon bacterial ecosystem and faecal metabolites profiles.
Design
Faecal samples collected during a double-blind, randomised, cross-over intervention study set up to assess the effect of inulin consumption on stool frequency in healthy adults with mild constipation were analysed. Faecal microbiota composition and metabolite profiles were linked to the study's clinical outcome as well as to quality-of-life measurements recorded.
Results
While faecal metabolite profiles were not significantly altered by inulin consumption, our analyses did detect a modest effect on global microbiota composition and specific inulin-induced changes in relative abundances of Anaerostipes, Bilophila and Bifidobacterium were identified. The observed decrease in Bilophila abundances following inulin consumption was associated with both softer stools and a favourable change in constipation-specific quality-of-life measures.
Conclusions
Ecosystem-wide analysis of the effect of a dietary intervention with prebiotic inulin-type fructans on the colon microbiota revealed that this effect is specifically associated with three genera, one of which (Bilophila) representing a promising novel target for mechanistic research.
Trial registration number
NCT02548247.
Angiopoietin-like protein 4 (ANGPTL4) is a lipoprotein lipase inhibitor that is involved in lipid metabolism and angiogenesis. Animal studies have suggested that the ANGPTL4 protein is modulated by the gut microbiota, possibly through increased concentrations of SCFA, such as C4, found in whole-fat milk or as a result of fermentation of inulin. This study investigated whether a standardised diet either high in fat content or supplemented with inulin powder would increase plasma ANGPTL4 in overweight men and whether this increase was mediated through a compositional change of the gut microbiota. The study had a crossover design with three arms, where participants were given a standardised isoenergetic diet supplemented with inulin powder, whole-fat milk or water (control). Plasma and urine samples were collected before and after each intervention period. Faecal samples and adipose tissue biopsies were collected after each intervention period. The study included twenty-one participants of whom eighteen completed the study. The dietary interventions did not change ANGPTL4 plasma concentration, nor was plasma ANGPTL4 associated with plasma lipids, TAG or NEFA concentration. The relative abundance of bifidobacteria following the inulin diet was higher, compared with the control diet. However, the changes in microbiota were not associated with plasma ANGPTL4 and the overall composition of the microbiota did not change between the dietary periods. Although weight was maintained throughout the dietary periods, weight was negatively associated with plasma ANGPTL4 concentration. In the adipose tissue, ANGPTL4 expression was correlated with leptin expression, but not with hypoxia-inducible factor 1α ( HIF-1α ) expression.
Introduction
Ingestion of poorly digested carbohydrates can induce functional gastrointestinal symptoms, which may be relieved by a diet low in fermentable oligo-, di-, mono-saccharides and polyols (FODMAPs). How dietary changes alter intestinal microbiota and gut function remains unclear. This abstract reports changes in microbiota seen in a randomised controlled trial presented at DDW 2014¹ and associations with colonic volume (CV), transit and dietary oligofructose.
Methods
All subjects (healthy adults) followed a low FODMAP diet for 7 days, supervised by a registered dietitian. They supplemented their diet with oligofructose (OF) or maltodextrin (MD) 7 g twice daily. CV and transit were assessed by magnetic resonance imaging pre- and post-intervention, as were fasting breath hydrogen(H2) and methane(CH4). Stool samples were collected before and after intervention for exploratory analysis of microbiota by 16 S Miseq sequencing.
Results
37 subjects (19 OF: 18 MD) completed the trial. All reported results were significant at corrected level p = 0.05 unless stated. At baseline the combined abundance of 3 bacterial genera - Bifidobacteria, Ruminococcus and Oscillospira - correlated positively with CV (r = 0.49) and transit time (r = 0.29, p < 0.1) while the levels of Faecalibacteria and Lachnospiraceae correlated negatively with CV (r = 0.57) and transit (r = 0.35). CV increased in both groups but changes in microbial composition were different. Relative abundance of Actinobacteria, predominantly Bifidobacterium, decreased in the MD + low FODMAP diet group while the relative abundance of Coprococcus, Oscillospira and uncultured Clostridia increased. Abundance of the latter two correlated with fasting breath CH4. In contrast Bifidobacteria and breath H2 both increased in the OF + low FODMAP diet group while abundance of Lachnospiraceae decreased.
Conclusion
Increase in Bifidobacteria and H2 confirm previous reports after OF or the low FODMAP diet. The increase in certain bacterial taxa after MD may result from polysaccharides included in the low FODMAP diet. Larger volumes were associated with specific bacteria but the mechanism is unclear. Future research should include assessment of volumes, transit and microbiota to provide new insights into the complex relationship between microbiology, physiology and therapy. View larger version:
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Abstract OC-088 Figure 1
Reference
1 Major, et al. OC-114, DDF 2014.
Disclosure of Interest
None Declared
Background & Aims: Studies in humans with overweight or obesity have reported that some prebiotics and synbiotics have beneficial effects on metabolic endotoxaemia and immune function. However, to date, no systematic review of controlled clinical trials assessed this topic. The aim of this study was to evaluate the effects of inulin-type fructans, galacto-oligosaccharides and related synbiotics on inflammatory markers in adults with overweight or obesity.
Methods: A systematic review of the literature was performed until November 6, 2015 in four electronic databases and reference lists of all included articles and relevant reviews in the field, without using any filter.
Results: Ten trials (six prebiotic and four synbiotic trials) representing 534 overweight/obese adults were included. All trials evaluated C-reactive protein or high-sensitivity C-reactive protein, four trials evaluated cytokines (two prebiotic and two synbiotic trials) and five trials evaluated endotoxin (four prebiotic and one synbiotic trials). Six trials (two with galacto-oligosaccharide, one with inulin and three with different synbiotics) showed a reduction on high-sensitivity C-reactive protein. Four trials (one with oligofructose-enriched inulin, one with inulin and two with different synbiotics) showed a reduction on interleukin-6 and/or tumor necrosis factor. Four trials (one with galacto-oligosaccharide, one with oligofructose-enriched inulin, one with inulin and one with synbiotic) showed a reduction on endotoxin.
Conclusions: Some prebiotics and synbiotics may have immunomodulatory action, however, more randomized controlled trials are needed to support the clinical use of inulin-type fructans, galacto-oligosaccharides or related synbiotics for the treatment of metabolic endotoxaemia or low grade inflammation in overweight/obese people.
Background:
It has been suggested that probiotics may improve gastrointestinal discomfort. Not all probiotics exhibit the same effects and consequently meta-analyses on probiotics should be confined to well-defined strains or strain combinations. The aim of this study was to evaluate the effectiveness of a probiotic fermented milk (PFM) that includes Bifidobacterium lactis (B. lactis) CNCM I-2494 and lactic acid bacteria on gastrointestinal discomfort in the general adult population.
Methods:
Double-blind randomized controlled trials in the general adult population comparing PFM with a control dairy product for at least 4 weeks were searched from multiple literature databases (up to February 2015). Meta-analyses using random-effects models, with individual participant data were undertaken to calculate an odds ratio (OR) or standard mean difference (SMD), with a 95% confidence interval (CI).
Results:
The search strategy identified 12,439 documents. Overall, three trials with a total of 598 adults (female = 96.5%) met the inclusion criteria. Consumption of the PFM product was associated with a significant improvement in overall gastrointestinal discomfort compared with the control product (OR = 1.48; 95% CI 1.07-2.05), with a number needed to treat (NNT) of 10.24 (95% CI 5.64-55.93). PFM was also superior to the control in reducing digestive symptoms, as measured using a composite score (SMD = -0.21; 95% CI -0.37 to -0.05). Sensitivity analyses produced similar results, and the heterogeneity between studies was minimal.
Conclusions:
This meta-analysis shows that the consumption of PFM with B. lactis CNCM I-2494 and lactic acid bacteria is associated with a modest but consistent and significant improvement of outcomes related to gastrointestinal discomfort in healthy adults.
Goal:
To determine the effect of a prebiotic chicory-derived inulin-type fructan on the tolerance of intestinal gas.
Background:
Subjects with gas-related complaints exhibit impaired handling of intestinal gas loads and we hypothesized that inulin would have a beneficial effect.
Study:
Placebo-controlled, parallel, randomized, double-blind trial. Subjects with abdominal symptoms and reduced tolerance of intestinal gas (selected by a pretest) received either inulin (8 g/d, n=18) or maltodextrin as a placebo (8 g/d, n=18) for 4 weeks. A gas challenge test (4 h jejunal gas infusion at 12 mL/min while measuring abdominal symptoms and gas retention for 3 h) was performed before and at the end of the intervention phase. Gastrointestinal symptoms and bowel habits (using daily questionnaires for 1 wk) and fecal bifidobacteria counts were measured before and at the end of the intervention.
Results:
Inulin decreased gas retention during the gas challenge test (by 22%; P=0.035 vs. baseline), while the placebo did not, but the intergroup difference was not statistically significant (P=0.343). Inulin and placebo reduced the perception of abdominal sensations in the gas challenge test to a similar extent (by 52% and 43%, respectively). Participants reported moderate gastrointestinal symptoms and normal bowel habits during baseline examination, and these findings remained unchanged in both groups during the intervention. Inulin led to a higher relative abundance of bifidobacteria counts (P=0.01 vs. placebo).
Conclusions:
A daily dose of inulin that promotes bifidobacteria growth and may improve gut function, is well tolerated by subjects with gastrointestinal complaints.
Little data exists on physiological outcomes associated with bacterial changes that occur after fructan feeding in healthy adults. To this end, we studied potential relationships between changes in gut bacteria composition and host physiological parameters after feeding 3 × 5 g/d of β2‐1 fructan (BF) or maltodextrin to a group of 13 male and 17 female healthy adults in a placebo‐controlled, double‐blinded, randomised crossover‐study consisting of two 28‐d exposures separated by a 14‐d washout. Fasting blood and 1‐d faecal collections were obtained on d0 and d28 of each phase. Well‐being and general health, as well as gastrointestinal symptoms, were determined by questionnaire. Serum lipopolysaccharides (LPS), faecal SCFA, faecal bifidobacteria and indigestion were higher during the BF‐supplemented phase. Numbers of circulating lymphocytes and macrophages were unchanged but BF supplementation decreased serum IL‐10 and increased serum IL‐4. In addition, circulating percentages of CD282 ⁺ /TLR2 ⁺ myeloid dendritic cells increased as did ex vivo responses to a TLR2 agonist. Culture‐based analysis of feces showed that 87 bacterial species encompassing 30 genera and four phyla were able to use BF as the sole carbon source. Fecal 16S rRNA analysis (26 subjects) showed BF reduced community richness. Two response patterns were observed: in 17/26 subjects, the relative abundance of Bacteroides was reduced and phylotypes within the Bifidobacterium , Faecalibacterium and the family Lachnospiraceae increased during the BF phase. In the remaining subjects, phylotypes aligning within the genera Bacteroides, Prevotella and to a lesser extent Bifidobacterium increased in abundance while abundance of phylotypes within the Faecalibacterium and the family Lachnospiraceae decreased during the BF phase. Few relationships between the faecal community composition and measured parameters were noted: (a) increases in Bacteroidetes relative abundance correlated with increased faecal propionate; (b) subjects in whom Bacteroidetes increased during the BF phase excreted more caproic acid (during both phases); and (c) subjects in whom Bacteroidetes decreased during the BF phase had higher LPS and LPS binding protein (during both phases). The most likely explanation for the observed patterns of faecal community change associated with the BF phase is a distal gut fermentation driven by differences in peptidyl nitrogen. We found no links between bacterial community changes and physiological changes nor was there evidence of physiological changes that would indicate a health benefit in these healthy subjects.
Support or Funding Information
This trial was undertaken with financial support from Agriculture and Agri‐Food Canada (RPBI# 1501, MK, GDI, LJY), Health Canada (SB), General Mills (MK), Alberta Innovates Bio Solutions (GDI), the Advanced Food and Materials Network (MK), and the National Science and Engineering Research Council (JMJG).
Protein intake exceeding requirements may benefit physiological processes and reduce the risk of sarcopenia in older adults. However, high protein, animal‐based diets may produce undesirable perturbations in microbiota resulting in inflammatory conditions. With declining diversity of colonic microbiota among older adults, prebiotics and probiotics may confer benefits in this cohort. The aim of this research was to examine the effects of a high protein (animal and plant protein) diet on microbiota profile and digestive health in healthy older adults, and the potential mitigating role of a prebiotic, multi‐strain probiotic or synbiotic. A double‐blind, crossover, placebo‐controlled feeding trial was conducted. Healthy older women (n=26; 73.7±5.6 y) were randomized to an 18‐week crossover study design consisting of 4 interventions: i) high protein diet (2.0–2.5 g/kg/d), ii) high protein diet with a multi‐strain probiotic (2×10 ¹⁰ CFU/d), iii.) high protein diet with inulin, and iv) high protein diet with symbiotic (inulin + probiotic). Each 14‐d intervention period consisted of the same eucaloric, high‐protein diet separated by 14‐day washout periods. Gastrointestinal health, including stool frequency and weekly gastrointestinal symptoms measured by Gastrointestinal Symptom Rating Scale (GSRS) were evaluated. Stools were collected during baseline, intervention and washout periods, and qPCR (polymerase chain reaction) and 16S rRNA gene sequencing was conducted. The results showed no phyla level changes, whereas high intra‐individual variations in genera and significant changes in operational taxonomic units (OTUs) were observed with treatments. Stool frequency was not different among periods. The high protein diet with interventions significantly increased GSRS scores of abdominal pain and indigestion syndromes, but not reflux, constipation and diarrhea syndrome, compared to baseline. The results of this study provide evidence that, contrary to the possible negative effects of a high protein, animal‐based diet, a high mixed protein diet did not have profound changes on microbiota in older women, a group that may benefit from the physiological benefits of higher protein intake.
Support or Funding Information
Lallemand Health Solutions; University of Florida
Childhood obesity has dramatically increased. Unfortunately, excess weight tends to persist into adulthood therefore therapies which target childhood obesity are essential in halting the obesity epidemic. Our objective was to determine if prebiotic fiber intake reduces body fat, pro‐inflammatory cytokines and insulin levels in overweight and obese children and to examine if this is due to a shift in gut microbiota composition. Overweight and obese children (蠅85 th BMI percentile) aged 7‐12y (n=39) were randomized to consume 8g/day of prebiotic fiber (1:1 inulin:oligofructose) or equicaloric placebo for 16 weeks. Body fat (measured by dual‐energy X‐ray absorptiometry), pro‐inflammatory cytokines and insulin (quantified from fasted blood serum), and gut microbiota (quantified from stool) were measured at baseline and week 16. Statistical significance was determined using non‐parametric Mann‐Whitney U‐Test at p蠄0.05. The first cohort (n=13) have completed the study with the final n=26 to finish December 2014. There was a trend for prebiotic fiber to reduce trunk body fat compared to placebo (‐1.42% vs +0.37%; p=0.15). Waist circumference (‐2.22 vs +0.03 cm), interferon gamma (‐1.4 vs +2.1 pg/mL) and fasted insulin levels (‐53.6 vs +155.3 pg/mL) were reduced with prebiotic and increased with placebo but not significantly. Bifidobacteria abundance significantly increased with prebiotic (p=0.03). Prebiotic fiber is a potential non‐invasive treatment option to reduce body fat in obese and overweight children by gut microbiota modulation.
Funded by BMO Financial Group/Alberta Children's Hospital Research Institute and Canadian Institutes of Health Research.
Background:
The low intake of dietary fiber compared to recommended amounts has been referred to as the dietary fiber gap. The addition of fiber to snack foods could favorably alter gut microbiota and help individuals meet intake recommendations.
Objectives:
Our objective was to examine the effect of low- and moderate-dose fiber-containing snack bars, comprising mainly chicory root inulin-type fructans (ITF), on gut microbiota in healthy adults with habitual low dietary fiber intake using 16S ribosomal RNA-based approaches.
Methods:
In 2 separate 4-wk, placebo-controlled, double-blind, crossover trials, 50 healthy adults with low dietary fiber intake were randomly assigned to receive isocaloric snack bars of either moderate-dose fiber (7 g/d) or control in Trial 1 (n = 25) or low-dose fiber (3 g/d) or control in Trial 2 (n = 25), with 4-wk washout periods. Fecal microbiota composition and inferred function, fecal SCFA concentration, gastrointestinal (GI) symptoms, dietary intake, and quality of life were measured.
Results:
Compared with the control group, the moderate-dose group showed significant differences across multiple microbial taxa, most notably an increased relative abundance of the Bifidobacterium genus from (mean ± SEM) 5.3% ± 5.9% to 18.7% ± 15.0%. With low-dose ITF, significant increases in Bifidobacterium were no longer present after correction for multiple comparisons but targeted analysis with qPCR showed a significant increase in Bifidobacterium. Predictive functional profiling identified changes in predicted function after intake of the moderate- but not the low-dose bar. Fecal SCFAs were affected by time but not treatment. There were no between-group differences in GI symptoms. Importantly, fiber intake increased significantly with the moderate- and low-dose bars.
Conclusions:
In healthy adults, adding 3 or 7 g ITF to snack bars increased Bifidobacterium, a beneficial member of the gut microbial community. The addition of ITF to food products could help reduce the dietary fiber gap prevalent in modern life.This trial was registered at clinicaltrials.gov as NCT03042494.
Background
The gut microbiota is altered in obesity and is strongly influenced by nutrients and xenobiotics. We have tested the impact of native inulin as prebiotic present in vegetables and added as a supplement on gut microbiota-related outcomes in obese patients. Metformin treatment was analyzed as a potential modulator of the response.
Methods
A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in 150 obese patients who received either 16 g/d native inulin versus maltodextrin, coupled to dietary advice to consume inulin-rich versus -poor vegetables for 3 months, respectively, in addition to dietary caloric restriction. Anthropometry, diagnostic imaging (abdominal CT-scan, fibroscan), food-behavior questionnaires, serum biology and fecal microbiome (primary outcome; 16S rDNA sequencing) were analyzed before and after the intervention.
Results
Both placebo and prebiotic interventions lowered energy intake, BMI, systolic blood pressure, and serum γ-GT. The prebiotic induced greater weight loss and additionally decreased diastolic blood pressure, AST and insulinemia. Metformin treatment compromised most of the gut microbiota changes and metabolic improvements linked to prebiotic intervention. The prebiotic modulated specific bacteria, associated with the improvement of anthropometry (i.e. a decrease in Desulfovibrio and Clostridium sensu stricto). A large increase in Bifidobacterium appears as a signature of inulin intake rather than a driver of prebiotic-linked biological outcomes.
Conclusions
Inulin-enriched diet is able to promote weight loss in obese patients, the treatment being related to gut microbiota characteristics. This treatment is more efficacious in patients who did not receive metformin as anti-diabetic drugs prior the intervention, supporting that both drug treatment and microbiota might be taken into account in personalized nutrition interventions.
Registered under ClinicalTrials.gov Identifier no NCT03852069.
Background:
Indoxyl sulfate (IS) and p-cresyl sulfate (pCS), 2 important protein-bound uremic toxins, are independent risk factors for cardiovascular disease in patients with end-stage renal disease. Indole and p-cresol are gut microbiome-generated precursors of IS and pCS.
Objective:
The aim of the present study was to determine whether inulin-type fructans (ITFs) reduce the production of indole and p-cresol by altering their producing bacteria in patients with peritoneal dialysis.
Methods:
Patients receiving peritoneal dialysis for >3 mo without diabetes and not using antibiotics were recruited to a randomized, double-blind, placebo-controlled, crossover trial of ITF intervention over 36 wk (12-wk washout). The primary outcomes were gut microbiome, fecal indole and p-cresol, indole-producing bacteria, p-cresol-producing bacteria, and serum IS and pCS. The secondary outcomes were fecal pH, 24-h urine, and dialysis removal of IS and pCS.
Results:
Of 21 individuals randomly assigned, 15 completed the study. The daily nutrient intakes, including protein, tryptophan, and tyrosine, were isostatic during the prebiotic, washout, and placebo intervention. There were no baseline differences in the outcomes of interest between treatments. For fecal indole, its concentrations did not change significantly in either treatment. However, there was a trend toward the treatment-by-time effect (P = 0.052), with a quantitative reduction in the ITF treatment and an increase in the control. The difference in the changes between the 2 treatments was significant (-10.07 ± 7.48 μg/g vs +13.35 ± 7.66 μg/g; P = 0.040). Similar to Bacteroides thetaiotaomicron, there was a difference over time between the 2 treatments, with a significant treatment and time interaction effect (P = 0.047). There were no treatment, time, or interaction effects for fecal p-cresol, serum IS and pCS, 24-h urine, and dialysis removal of IS and pCS.
Conclusions:
Our results suggested that ITFs restricted the increase in gut microbiome-generated indole in patients with peritoneal dialysis. This trial was registered at http://www.chictr.org.cn/showproj.aspx?proj=21228 as ChiCTR-INR-17013739.
Objective
Meta-analysis is of fundamental importance to obtain an unbiased assessment of the available evidence. In general, the use of meta-analysis has been increasing over the last three decades with mental health as a major research topic. It is then essential to well understand its methodology and interpret its results. In this publication, we describe how to perform a meta-analysis with the freely available statistical software environment R, using a working example taken from the field of mental health.
Methods
R package meta is used to conduct standard meta-analysis. Sensitivity analyses for missing binary outcome data and potential selection bias are conducted with R package metasens. All essential R commands are provided and clearly described to conduct and report analyses.
Results
The working example considers a binary outcome: we show how to conduct a fixed effect and random effects meta-analysis and subgroup analysis, produce a forest and funnel plot and to test and adjust for funnel plot asymmetry. All these steps work similar for other outcome types.
Conclusions
R represents a powerful and flexible tool to conduct meta-analyses. This publication gives a brief glimpse into the topic and provides directions to more advanced meta-analysis methods available in R.
The revised edition of the Handbook offers the only guide on how to conduct, report and maintain a Cochrane Review ? The second edition of The Cochrane Handbook for Systematic Reviews of Interventions contains essential guidance for preparing and maintaining Cochrane Reviews of the effects of health interventions. Designed to be an accessible resource, the Handbook will also be of interest to anyone undertaking systematic reviews of interventions outside Cochrane, and many of the principles and methods presented are appropriate for systematic reviews addressing research questions other than effects of interventions. This fully updated edition contains extensive new material on systematic review methods addressing a wide-range of topics including network meta-analysis, equity, complex interventions, narrative synthesis, and automation. Also new to this edition, integrated throughout the Handbook, is the set of standards Cochrane expects its reviews to meet. Written for review authors, editors, trainers and others with an interest in Cochrane Reviews, the second edition of The Cochrane Handbook for Systematic Reviews of Interventions continues to offer an invaluable resource for understanding the role of systematic reviews, critically appraising health research studies and conducting reviews.
Probiotics and prebiotics are microbiota-management tools for improving host health. They target gastrointestinal effects via the gut, although direct application to other sites such as the oral cavity, vaginal tract and skin is being explored. Here, we describe gut-derived effects in humans. In the past decade, research on the gut microbiome has rapidly accumulated and has been accompanied by increased interest in probiotics and prebiotics as a means to modulate the gut microbiota. Given the importance of these approaches for public health, it is timely to reiterate factual and supporting information on their clinical application and use. In this Review, we discuss scientific evidence on probiotics and prebiotics, including mechanistic insights into health effects. Strains of Lactobacillus, Bifidobacterium and Saccharomyces have a long history of safe and effective use as probiotics, but Roseburia spp., Akkermansia spp., Propionibacterium spp. and Faecalibacterium spp. show promise for the future. For prebiotics, glucans and fructans are well proven, and evidence is building on the prebiotic effects of other substances (for example, oligomers of mannose, glucose, xylose, pectin, starches, human milk and polyphenols).
Inulin is a soluble dietary fibre, also classified as a prebiotic, extracted from chicory roots. The present study aimed to determine the effect of consumption of native chicory inulin on the stool frequency of middle-aged to older adults (40-75 years old) with uncomfortably but not clinically relevant low stool frequency, specified as two to four days without bowel movements per week. Two randomised, double blind, placebo-controlled crossover trials were conducted using similar protocols in differing populations. Trial A was conducted in Amsterdam, The Netherlands and subsequently Trial B was conducted in Newcastle, United Kingdom. Both trials involved supplementation for 5 weeks with 10 g per day of inulin or placebo, a washout period of 2 weeks, and then crossed over to receive the other treatment. In Trial B, faecal gut microbiota composition was assessed using 16S rRNA gene sequencing. In Trial A, which 10 volunteers completed, the stool frequency was significantly increased to an average 4.9 ± 0.23 (SEM) times per week during inulin periods versus 3.6 ± 0.25 in the periods with placebo (p = 0.01). In contrast, in Trial B which 20 volunteers completed, there was no significant effect of the inulin on stool frequency (7.5 ± 2.1 times per week with inulin, 8.1 ± 3.0 with placebo, p = 0.35). However, many subjects in Trial B had a stool frequency >5 per week also for the placebo period, in breach of the inclusion criteria. Combining the data of 16 low stool frequency subjects from Trials A and B showed a significant effect of inulin to increase stool frequency from 4.1 to 5.0 per week (p = 0.032). Regarding secondary outcomes, stool consistency was significantly softer with inulin treatment compared to placebo periods, it increased 0.29 on the Bristol stool scale (p = 0.008) when data from all subjects of Trials A and B were combined. No other differences in bowel habit parameters due to inulin consumption were significant. None of the differences in specific bacterial abundance, alpha or beta diversity were significant, however the trends were in directions consistent with published studies on other types of inulin. We conclude that 10 g per day of native chicory inulin can increase stool frequency in subjects with low stool frequency.
Background:
Patients with type 1 diabetes (T1D) have lower microbiota diversity and distinct gut microbial profiles that have been linked to changes in intestinal permeability (IP). Prebiotics are non-digestible carbohydrates that alter gut microbiota and could potentially improve glycemic control, reduce IP and thereby insulin sensitivity.
Purpose:
To determine the effect of prebiotic on glycemic control, gut microbiota, and IP in children with T1D.
Methods:
A randomized, placebo controlled trial in children 8-17 years with T1D using placebo or prebiotic oligofructose-enriched inulin for 12 weeks. Baseline, 3-months, and 6-months assessments included: A1C, C-peptide, gut microbiota, IP, frequency of diabetic ketoacidosis (DKA), and severe hypoglycemia.
Results:
43 subjects were randomized and 38 completed the study. The groups were similar at baseline: prebiotic (N=17), age 12.5 years (SD 2.8), A1C 8.02% (SD 0.82); placebo (N=21), age 12.0 years (SD 2.6), A1C 8.08% (SD 0.91). No significant differences were found in frequency of DKA or severe hypoglycemia. At 3-months, c-peptide was significantly higher (p=0.029) in the group that received prebiotics, which was accompanied by a modest improvement in IP (p=0.076). There was a significant increase in the relative abundance of Bifidobacterium within the prebiotic group at 3-months which was no longer present after the 3 month wash out. The placebo group had significantly higher relative abundance of Streptococcus, Roseburia inulinovorans, Terrisporobacter and Faecalitalea compared to the prebiotic group at 3 months.
Conclusion:
Prebiotics are a potentially novel, inexpensive, low-risk treatment addition for T1D that may improve glycemic control. Further larger scale trials are needed.
Diet is a key determinant of human gut microbiome variation. However, the fine-scale relationships between daily food choices and human gut microbiome composition remain unexplored. Here, we used multivariate methods to integrate 24-h food records and fecal shotgun metagenomes from 34 healthy human subjects collected daily over 17 days. Microbiome composition depended on multiple days of dietary history and was more strongly associated with food choices than with conventional nutrient profiles, and daily microbial responses to diet were highly personalized. Data from two subjects consuming only meal replacement beverages suggest that a monotonous diet does not induce microbiome stability in humans, and instead, overall dietary diversity associates with microbiome stability. Our work provides key methodological insights for future diet-microbiome studies and suggests that food-based interventions seeking to modulate the gut microbiota may need to be tailored to the individual microbiome. Trial Registration: ClinicalTrials.gov: NCT03610477.
Background:
Irritable bowel syndrome (IBS) and other functional bowel disorders (FBDs) are prevalent disorders with altered microbiota. Prebiotics positively augment gut microbiota and may offer therapeutic potential.
Objectives:
The aim of this study was to investigate the effect of prebiotics compared with placebo on global response, gastrointestinal symptoms, quality of life (QoL), and gut microbiota, via systematic review and meta-analysis of randomized controlled trials (RCTs) in adults with IBS and other FBDs.
Methods:
Studies were identified using electronic databases, back-searching reference lists, and hand-searching abstracts. RCTs that compared prebiotics to placebo in adults with IBS or other FBDs were included. Two reviewers independently performed screening, data extraction, and bias assessment. Outcome data were synthesized as ORs, weighted mean differences (WMDs) or standardized mean differences (SMDs) with the use of a random-effects model. Subanalyses were performed for type of FBD and dose, type, and duration of prebiotic.
Results:
Searches identified 2332 records, and 11 RCTs were eligible (729 patients). The numbers responding were 52/97 (54%) for prebiotic and 59/94 (63%) for placebo, with no difference between groups (OR: 0.62; 95% CI: 0.07, 5.69; P = 0.67). Similarly, no differences were found for severity of abdominal pain, bloating and flatulence, and QoL score between prebiotics and placebo. However, flatulence severity was improved by prebiotics at doses ≤6 g/d (SMD: -0.35; 95% CI: -0.71, 0.00; P = 0.05) and by non-inulin-type fructan prebiotics (SMD: -0.34; 95% CI: -0.66, -0.01; P = 0.04), while inulin-type fructans worsened flatulence (SMD: 0.85; 95% CI: 0.23, 1.47; P = 0.007). Prebiotics increased absolute abundance of bifidobacteria (WMD: 1.16 log10 copies of the 16S ribosomal RNA gene; 95% CI: 0.06, 2.26; P = 0.04). No studies were at low risk of bias across all bias categories.
Conclusions:
Prebiotics do not improve gastrointestinal symptoms or QoL in patients with IBS or other FBDs, but they do increase bifidobacteria. Variations in prebiotic type and dose impacted symptom improvement or exacerbation. This review was registered at PROSPERO as CRD42017074072.
Dysbiotic gut microbiota have been implicated in human disease. Diet-based therapeutic strategies have been used to manipulate the gut microbiota towards a more favourable profile. However, it has been demonstrated that large inter-individual variability exists in gut microbiota response to a dietary intervention. The primary objective of this study was to investigate whether habitually low dietary fibre (LDF) v . high dietary fibre (HDF) intakes influence gut microbiota response to an inulin-type fructan prebiotic. In this randomised, double-blind, placebo-controlled, cross-over study, thirty-four healthy participants were classified as LDF or HDF consumers. Gut microbiota composition (16S rRNA bacterial gene sequencing) and SCFA concentrations were assessed following 3 weeks of daily prebiotic supplementation (Orafti ® Synergy 1; 16 g/d) or placebo (Glucidex ® 29 Premium; 16 g/d), as well as after 3 weeks of the alternative intervention, following a 3-week washout period. In the LDF group, the prebiotic intervention led to an increase in Bifidobacterium ( P =0·001). In the HDF group, the prebiotic intervention led to an increase in Bifidobacterium ( P <0·001) and Faecalibacterium ( P =0·010) and decreases in Coprococcus ( P =0·010) , Dorea ( P =0·043) and Ruminococcus (Lachnospiraceae family) ( P =0·032). This study demonstrates that those with HDF intakes have a greater gut microbiota response and are therefore more likely to benefit from an inulin-type fructan prebiotic than those with LDF intakes. Future studies aiming to modulate the gut microbiota and improve host health, using an inulin-type fructan prebiotic, should take habitual dietary fibre intake into account.
Healthy adults ( n 30) participated in a placebo-controlled, randomised, double-blinded, cross-over study consisting of two 28 d treatments ( β 2-1 fructan or maltodextrin; 3×5 g/d) separated by a 14-d washout. Subjects provided 1 d faecal collections at days 0 and 28 of each treatment. The ability of faecal bacteria to metabolise β 2-1 fructan was common; eighty-seven species (thirty genera, and four phyla) were isolated using anaerobic medium containing β 2-1 fructan as the sole carbohydrate source. β 2-1 fructan altered the faecal community as determined through analysis of terminal restriction fragment length polymorphisms and 16S rRNA genes. Supplementation with β 2-1 fructan reduced faecal community richness, and two patterns of community change were observed. In most subjects, β 2-1 fructan reduced the content of phylotypes aligning within the Bacteroides , whereas increasing those aligning within bifidobacteria, Faecalibacterium and the family Lachnospiraceae. In the remaining subjects, supplementation increased the abundance of Bacteroidetes and to a lesser extent bifidobacteria, accompanied by decreases within the Faecalibacterium and family Lachnospiraceae. β 2-1 Fructan had no impact on the metagenome or glycoside hydrolase profiles in faeces from four subjects. Few relationships were found between the faecal bacterial community and various host parameters; Bacteroidetes content correlated with faecal propionate, subjects whose faecal community contained higher Bacteroidetes produced more caproic acid independent of treatment, and subjects having lower faecal Bacteroidetes exhibited increased concentrations of serum lipopolysaccharide and lipopolysaccharide binding protein independent of treatment. We found no evidence to support a defined health benefit for the use of β 2-1 fructans in healthy subjects.
Scope:
Independently, prebiotics and dietary protein have been shown to improve weight loss and/or alter appetite. Our objective was to determine the effect of combined prebiotic and whey protein on appetite, body composition and gut microbiota in adults with overweight/obesity.
Methods and results:
In a 12 week, placebo-controlled, double-blind study, 125 adults with overweight/obesity were randomly assigned to receive isocaloric snack bars of: 1) Control; 2) Inulin-type fructans (ITF); 3) Whey protein; 4) ITF + Whey protein. Appetite, body composition and gut microbiota composition/genetic potential were assessed. Compared to Control, body fat was significantly reduced in the Whey protein group at 12wks. Hunger, desire to eat and prospective food consumption were all lower with ITF, Whey protein and ITF + Whey protein compared to Control at 12 wks. Microbial community structure differed from 0 to 12 wks in the ITF and ITF +Whey Protein groups (i.e. increased Bifidobacterium) but not Whey Protein or Control. Changes in microbial genetic potential were seen between Control and ITF-containing treatments.
Conclusions:
Adding ITF, whey protein or both to snack bars improved several aspects of appetite control. Changes in gut microbiota may explain in part the effects of ITF but likely not whey protein. This article is protected by copyright. All rights reserved.