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Gut microbiota alterations are intimately linked to chronic constipation upon aging. We investigated the role of targeted changes in the gut microbiota composition in the relief of constipation symptoms after rhubarb extract (RE) supplementation in middle-aged volunteers. Subjects (95% women, average 58 years old) were randomized to three groups treated with RE at two different doses determined by its content of rhein (supplementation of 12.5 mg and 25 mg per day) vs. placebo (maltodextrin) for 30 days. We demonstrated that daily oral supplementation of RE for 30 days was safe even at the higher dose. Stool frequency and consistency, and perceived change in transit problem, transit speed and difficulty in evacuating, investigated by validated questionnaires, were improved in both groups of RE-treated volunteers compared to placebo. Higher abundance of Lachnospiraceae (mainly Roseburia and Agathobacter) only occurred after RE treatment when present at low levels at baseline, whereas an opposite shift in short-chain fatty acid (SCFA) levels was observed in both RE-treated groups (increase) and placebo (decrease). Fecal Lachnospiraceae and SCFA were positively correlated with stool consistency. This study demonstrates that RE supplementation promotes butyrate-producing bacteria and SCFA, an effect that could contribute to relieving chronic constipation in middle-aged persons.

The prevalence of overweight and obesity has reached epidemic proportions globally over the past few decades. The search for new management approaches continues and among them, targeting the gut microbiota can be envisioned. To date, numerous data showed the involvement of the gut microbes in the regulation and control of host metabolism. There are also increasing evidences highlighting the interactions between environmental factors, intrinsic factors, gut microbiota, and metabolic diseases. Diet emerges as the most relevant factor influencing the gut microbiome. Eating habits, as well as short-term consumption of specific diets, alter the gut microbiota composition. Moreover, nutritional disorders are associated with changes of the gut microbiota composition and/or function, as shown in obesity or type 2 diabetic patients versus healthy lean subjects. Targeting the gut microbiota for improving metabolic health appears as a new approach to manage obesity and cardio-metabolic risk. In this review, we have detailed the results of human interventions targeting the gut microbiome by prebiotic supplementation, prebiotics being defined as "substrates that are selectively utilized by the host microorganisms conferring a health benefit." If the potential benefit of this approach is obvious in preclinical models, the efficacy of prebiotics in humans is less reproducible. The inter-individual variability of response to dietary intervention can be dependent on the gut microbiota and we summarized the basal gut microbiota characteristics driving the metabolic response to dieting, prebiotic and dietary fiber intervention in the context of obesity and related metabolic diseases.

Numerous studies in humans and animal models describe disturbances of the gut microbial ecosystem associated with adiposity and hallmarks of the metabolic syndrome, including hepatic and cardiovascular diseases. The manipulation of the microbiome, which is largely influenced by the diet, appears as an innovative therapeutic tool to prevent or control obesity and related diseases. This review describes the impact of nutrients on the gut microbiota composition and/or function and when available, the consequences on host physiology. A special emphasis is made on the contribution of bacterial-derived metabolites in the regulation of key gut functions that may explain their systemic effect.

Objective: The gut microbiota has been proposed as an interesting therapeutic target for metabolic disorders. Inulin as a prebiotic has been shown to lessen obesity and related diseases. The aim of the current study was to investigate whether preintervention gut microbiota characteristics determine the physiological response to inulin. Design: The stools from four obese donors differing by microbial diversity and composition were sampled before the dietary intervention and inoculated to antibiotic-pretreated mice (hum-ob mice; humanised obese mice). Hum-ob mice were fed with a high-fat diet and treated with inulin. Metabolic and microbiota changes on inulin treatment in hum-ob mice were compared with those obtained in a cohort of obese individuals supplemented with inulin for 3 months. Results: We show that hum-ob mice colonised with the faecal microbiota from different obese individuals differentially respond to inulin supplementation on a high-fat diet. Among several bacterial genera, Barnesiella, Bilophila, Butyricimonas, Victivallis, Clostridium XIVa, Akkermansia, Raoultella and Blautia correlated with the observed metabolic outcomes (decrease in adiposity and hepatic steatosis) in hum-ob mice. In addition, in obese individuals, the preintervention levels of Anaerostipes, Akkermansia and Butyricicoccus drive the decrease of body mass index in response to inulin. Conclusion: These findings support that characterising the gut microbiota prior to nutritional intervention with prebiotics is important to increase the positive outcome in the context of obesity and metabolic disorders., SCOPUS: ar.j, info:eu-repo/semantics/published

The prevalence of overweight and obesity has reached epidemic proportions globally over the past few decades. The search for new management approaches continues and among them, targeting the gut microbiota can be envisioned. To date, numerous data showed the involvement of the gut microbes in the regulation and control of host metabolism. There are also increasing evidences highlighting the interactions between environmental factors, intrinsic factors, gut microbiota, and metabolic diseases. Diet emerges as the most relevant factor influencing the gut microbiome. Eating habits, as well as short-term consumption of specific diets, alter the gut microbiota composition. Moreover, nutritional disorders are associated with changes of the gut microbiota composition and/or function, as shown in obesity or type 2 diabetic patients versus healthy lean subjects. Targeting the gut microbiota for improving metabolic health appears as a new approach to manage obesity and cardio-metabolic risk. In this review, we have detailed the results of human interventions targeting the gut microbiome by prebiotic supplementation, prebiotics being defined as "substrates that are selectively utilized by the host microorganisms conferring a health benefit." If the potential benefit of this approach is obvious in preclinical models, the efficacy of prebiotics in humans is less reproducible. The inter-individual variability of response to dietary intervention can be dependent on the gut microbiota and we summarized the basal gut microbiota characteristics driving the metabolic response to dieting, prebiotic and dietary fiber intervention in the context of obesity and related metabolic diseases.

Obesity is associated with an increased risk of several neurological and psychiatric diseases, but few studies report the contribution of biological features in the occurrence of mood disorders in obese patients. The aim of the study is to evaluate the potential links between serum metabolomics and gut microbiome, and mood disturbances in a cohort of obese patients. Psychological, biological characteristics and nutritional habits were evaluated in 94 obese subjects from the Food4Gut study stratified according to their mood score assessed by the Positive and Negative Affect Schedule (PANAS). The fecal gut microbiota and plasma non-targeted metabolomics were analysed. Obese subjects with increased negative mood display elevated levels of Coprococcus as well as decreased levels of Sutterella and Lactobacillus. Serum metabolite profile analysis reveals in these subjects altered levels of several amino acid-derived metabolites, such as an increased level of L-histidine and a decreased in phenylacetylglutamine, linked to altered gut microbiota composition and function rather than to differences in dietary amino acid intake. Regarding clinical profile, we did not observe any differences between both groups. Our results reveal new microbiota-derived metabolites that characterize the alterations of mood in obese subjects, thereby allowing to propose new targets to tackle mood disturbances in this context. Food4gut, clinicaltrial.gov: NCT03852069.

International audience; With the increasing demand for alternative solutions to replace or optimize the use of synthetic fertilizers and pesticides, the inoculation of bacteria that can contribute to the growth and health of plants (PGPR) is essential. The properties classically sought in PGPR are the production of phytohormones and other growth-promoting molecules, and more rarely the production of exopolysaccharides. We compared the effect of two strains of exopolysaccharide-producing Rhizobium alamii on rapeseed grown in a calcareous silty-clay soil under water stress conditions or not. The effect of factors ‘water stress’ and ‘inoculation’ were evaluated on plant growth parameters and the diversity of microbiota associated to root and root-adhering soil compartments. Water stress resulted in a significant decrease in leaf area, shoot biomass and RAS/RT ratio (root-adhering soil/root tissues), as well as overall beta-diversity. Inoculation with R. alamii YAS34 and GBV030 under water-stress conditions produced the same shoot dry biomass compared to uninoculated treatment in absence of water stress, and both strains increased shoot biomass under water-stressed conditions (+7% and +15%, respectively). Only R. alamii GBV030 significantly increased shoot biomass under unstressed or water-stressed conditions compared to the non-inoculated control (+39% and +15%, respectively). Alpha-diversity of the root-associated microbiota after inoculation with R. alamii YAS34 was significantly reduced. Beta-diversity was significantly modified after inoculation with R. alamii GBV030 under unstressed conditions. LEfSe analysis identified characteristic bacterial families, Flavobacteriaceae and Comamonadaceae, in the RT and RAS compartments for the treatment inoculated by R. alamii GBV030 under unstressed conditions, as well as Halomonadaceae (RT) and several species belonging to Actinomycetales (RAS). We showed that R. alamii GBV030 had a PGPR effect on rapeseed growth, increasing its tolerance to water stress, probably involving its capacity to produce exopolysaccharides, and other plant growth-promoting (PGP) traits.

This review presents mechanistic studies performed in vitro and in animal models, as well as data obtained in patients that contribute to a better understanding of the impact of nutrients interacting with the gut microbiota on metabolic and behavioural alterations linked to obesity. The gut microbiota composition and function are altered in several pathological conditions including obesity and related diseases i.e. non-alcoholic fatty liver diseases (NAFLD). The gut–liver axis is clearly influenced by alterations of the gut barrier that drives inflammation. In addition, recent papers propose that specific metabolites issued from the metabolic cooperation between the gut microbes and host enzymes, modulate inflammation and gene expression in the liver. This review illustrates how dietary intervention with prebiotics or probiotics influences host energy metabolism and inflammation. Indeed, intervention studies are currently underway in obese and NAFLD patients to unravel the relevance of the changes in gut microbiota composition in the management of metabolic and behavioural disorders by nutrients interacting with the gut microbiota. In conclusion, diet is among the main triggers of NAFLD and the gut microbiota is modified accordingly, underlining the importance of the concomitant study of the nutrients and microbial impact on liver health and metabolism, in order to propose innovative, clinically relevant, therapeutic approaches.

Berberine and curcumin, used as food additives or food supplements, possess interesting anti-inflammatory and antioxidant properties. We tested the potential protective effect of both phytochemicals in genetically obese mice and we determined whether these effects can be related to the modulation of gut functions and microbiota. Ob/ob mice were fed a standard diet supplemented with or without 0.1% berberine and/or 0.3% curcumin for 4 weeks. By using targeted qPCR, we found that cecal content of Bifidobacterium spp. and Akkermansia spp. increased mainly upon berberine supplementation. Genes involved in innate immunity (Pla2g2a), mucus production (Muc2) and satietogenic peptide production (Gcg and Pyy) were upregulated in the colon of mice treated with both phytochemicals. Berberine supplementation alone reduced food intake, body weight gain, hypertriglyceridemia and hepatic inflammatory and oxidative stress markers, thus lessening hepatic injury. The increase in Bifidobacterium spp. and Akkermansia spp. was correlated with the improvement of gut barrier function and with the improvement of hepatic inflammatory and oxidative stresses in obese mice. These data support the fact that non-carbohydrate phytochemicals may modulate the gut microbiota in obesity and related gut and hepatic alterations.

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International audience; Background : The gut microbiota plays a role in the occurrence of nonalcoholic fatty liver disease (NAFLD), notably through the production of bioactive metabolites. Indole, a bacterial metabolite of tryptophan, has been proposed as a pivotal metabolite modulating inflammation, metabolism, and behavior.Objectives : The aim of our study was to mimic an upregulation of intestinal bacterial indole production and to evaluate its potential effect in vivo in 2 models of NAFLD.Methods : Eight-week-old leptin-deficient male ob/ob compared with control ob/+ mice (experiment 1), and 4–5-wk-old C57BL/6JRj male mice fed a low-fat (LF, 10 kJ%) compared with a high-fat (HF, 60 kJ%) diet (experiment 2), were given plain water or water supplemented with a physiological dose of indole (0.5 mM, n ≥6/group) for 3 wk and 3 d, respectively. The effect of the treatments on the liver, intestine, adipose tissue, brain, and behavior was assessed.Results : Indole reduced hepatic expression of genes involved in inflammation [C-C motif chemokine ligand 2 (Ccl2), C-X-C motif chemokine ligand 2 (Cxcl2); 3.3- compared with 5.0-fold, and 2.4- compared with 3.3-fold of control ob/+ mice, respectively, P < 0.05], and in macrophage activation [Cd68, integrin subunit α X (Itgax); 2.1- compared with 2.5-fold, and 5.0- compared with 6.4-fold of control ob/+ mice, respectively, P < 0.01] as well as markers of hepatic damage (alaninine aminotransferase; −32%, P < 0.001) regardless of genotype in experiment 1. Indole had no effect on hepatic inflammation in mice fed the LF or HF diet in experiment 2. Indole did not change hepatic lipid content, anxiety-like behavior, or inflammation in the ileum, adipose tissue, and brain in experiment 1.Conclusions : Our results support the efficacy of indole to reduce hepatic damage and associated inflammatory response and macrophage activation in ob/ob mice. These modifications appear to be attributable to direct effects of indole on the liver, rather than through effects on the adipose tissue or intestinal barrier.

Obesity could lead to metabolic dysfunction-associated fatty liver disease (MAFLD), which severity could be linked to muscle and gut microbiota disturbances. Our prospective study enrolled 52 obese patients whose MAFLD severity was estimated by transient elastography. Patients with severe steatosis (n = 36) had higher ALAT values, fasting blood glucose levels as well as higher visceral adipose tissue area and skeletal muscle index evaluated by computed tomography. Patients with fibrosis (n = 13) had higher ASAT values, increased whole muscle area and lower skeletal muscle density index. In a multivariate logistic regression analysis, myosteatosis was the strongest factor associated with fibrosis. Illumina sequencing of 16S rRNA gene amplicon was performed on fecal samples. The relative abundance of fecal Clostridium sensu stricto was significantly decreased with the presence of liver fibrosis and was negatively associated with liver stiffness measurement and myosteatosis. In addition, 19 amplicon sequence variants were regulated according to the severity of the disease. Linear discriminant analysis effect size (LEfSe) also highlighted discriminant microbes in patients with fibrosis, such as an enrichment of Enterobacteriaceae and Escherichia/Shigella compared to patients with severe steatosis without fibrosis. All those data suggest a gut-liver-muscle axis in the pathogenesis of MAFLD complications.

Several studies suggest that microbial alterations (dysbiosis) are intimately linked to chronic inflammation occurring upon aging. The aim of this study was to investigate the potential interest of a synbiotic approach (co-administration of a probiotic bacteria and a prebiotic dietary fibre) to improve gastrointestinal wellness and inflammatory markers in middle-aged people. Middle-aged subjects were randomized to take synbiotic (Bifidobacterium animalis lactis and fructo-oligosaccharides (FOS)) or placebo for 30 days. Stool frequency and consistency were improved in both placebo and synbiotic-treated volunteers while the synbiotic treatment significantly decreased the number of days with abdominal discomfort. Synbiotic treatment had no impact on mood dimensions, quality of life scores or the overall composition of the gut microbiota (16S rRNA gene sequencing of DNA extracted from stool). Importantly, plasma proinflammatory cytokines (interleukin (IL)-6, IL-8, IL-17a and interferon-gamma (IFNγ)) were significantly lower after 30 days of synbiotic supplementation. This effect appears to be independent of the gut barrier function. This study demonstrates that a combination of B. animalis lactis and the well-known prebiotic FOS could be a promising synbiotic strategy to decrease inflammatory status with improvement of gut disorders in middle-aged people.

International audience; BACKGROUND: Current data suggest that dietary fibre (DF) interaction with the gut microbiota largely contributes to their physiological effects. The bacterial fermentation of DF leads to the production of metabolites, most of them are volatile. This study analyzed the breath volatile metabolites (BVM) profile in healthy individuals (n=15) prior and after a 3-week intervention with chitin-glucan (CG, 4.5 g/day), an insoluble fermentable DF. METHODS: The present exploratory study presents the original data related to the secondary outcomes, notably the analysis of BVM. BVM were analyzed throughout the test days -in fasting state and after standardized meals - using selected ion flow tube mass spectrometry (SIFT-MS). BVM production was correlated to the gut microbiota composition (Illumina sequencing, primary outcome), analyzed before and after the intervention. FINDINGS: The data reveal that the post-prandial state versus fasting state is a key determinant of BVM fingerprint. Correlation analyses with fecal microbiota spotlighted butyrate-producing bacteria, notably Faecalibacterium, as dominant bacteria involved in butyrate and other BVM expiration. CG intervention promotes interindividual variations of fasting BVM, and decreases or delays the expiration of most exhaled BVM in favor of H(2) expiration, without any consequence on gastrointestinal tolerance. INTERPRETATION: Assessing BVM is a non-invasive methodology allowing to analyze the influence of DF intervention on the gut microbiota. FUNDING: FiberTAG project was initiated from a European Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL) and was supported by the Service Public de Wallonie (SPW-EER, convention 1610365, Belgium).

Purpose Inulin-type fructans (ITF) are prebiotic dietary fibre (DF) that may confer beneficial health effects, by interacting with the gut microbiota. We have tested the hypothesis that a dietary intervention promoting inulin intake versus placebo influences fecal microbial-derived metabolites and markers related to gut integrity and inflammation in obese patients. Methods Microbiota (16S rRNA sequencing), long- and short-chain fatty acids (LCFA, SCFA), bile acids, zonulin, and calprotectin were analyzed in fecal samples obtained from obese patients included in a randomized, placebo-controlled trial. Participants received either 16 g/d native inulin (prebiotic n = 12) versus maltodextrin (placebo n = 12), coupled to dietary advice to consume inulin-rich versus inulin-poor vegetables for 3 months, in addition to dietary caloric restriction. Results Both placebo and prebiotic interventions lowered energy and protein intake. A substantial increase in Bifidobacterium was detected after ITF treatment ( q = 0.049) supporting our recent data obtained in a larger cohort. Interestingly, fecal calprotectin, a marker of gut inflammation, was reduced upon ITF treatment. Both prebiotic and placebo interventions increased the ratio of tauro-conjugated/free bile acids in feces. Prebiotic treatment did not significantly modify fecal SCFA content but it increased fecal rumenic acid, a conjugated linoleic acid ( cis -9, trans -11 CLA) with immunomodulatory properties, that correlated notably to the expansion of Bifidobacterium ( p = 0.031; r = 0.052). Conclusions Our study demonstrates that ITF-prebiotic intake during 3 months decreases a fecal marker of intestinal inflammation in obese patients. Our data point to a potential contribution of microbial lipid-derived metabolites in gastro-intestinal dysfunction related to obesity. ClinicalTrials.gov Identifier NCT03852069 (February 22, 2019 retrospectively, registered)., SCOPUS: ar.j, info:eu-repo/semantics/published

International audience; The fermentation of dietary fibre (DF) leads to the production of bioactive metabolites, the most volatile ones being excreted in the breath. The aim of this study was to analyze the profile of exhaled breath volatile metabolites (BVM) and gastrointestinal symptoms in healthy volunteers after a single ingestion of maltodextrin (placebo) versus chitin-glucan (CG), an insoluble DF previously shown to be fermented into short-chain fatty acids (SCFA) by the human microbiota in vitro. Maltodextrin (4.5 g at day 0) or CG (4.5 g at day 2) were added to a standardized breakfast in fasting healthy volunteers (n = 15). BVM were measured using selected ion flow tube mass spectrometry (SIFT-MS) throughout the day. A single ingestion of 4.5 g CG did not induce significant gastrointestinal discomfort. Untargeted metabolomics analysis of breath highlighted that 13 MS-fragments (among 408 obtained from ionizations of breath) discriminated CG versus maltodextrin acute intake in the posprandial state. The targeted analysis revealed that CG increased exhaled butyrate and 5 other BVM - including the microbial metabolites 2,3-butanedione and 3-hydroxybutanone - with a peak observed 6 h after CG intake. Correlation analyses with fecal microbiota (Illumina 16S rRNA sequencing) spotlighted Mitsuokella as a potential genus responsible for the presence of butyric acid, triethylamine and 3-hydroxybutanone in the breath. In conclusion, measuring BMV in the breath reveals the microbial signature of the fermentation of DF after a single ingestion. This protocol allows to analyze the time-course of released bioactive metabolites that could be proposed as new biomarkers of DF fermentation, potentially linked to their biological properties. Trial registration: Clinical Trials NCT03494491. Registered 11 April 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03494491.

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 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 efficiency 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., info:eu-repo/semantics/published

Background: The fermentation of dietary fibers (DF) leads to the production of bioactive metabolites, the most volatile ones being excreted in the breath. The aim of this study was to analyze the profile of exhaled breath volatile metabolites (BVM) and gastro-intestinal symptoms in healthy volunteers after a single ingestion of maltodextrin (placebo) versus chitin-glucan (CG), an insoluble DF previously shown to be fermented into short-chain fatty acids (SCFA) by the human microbiota in vitro.Methods: 4.5 g maltodextrin (day 0) or 4.5 g CG (day 2) were added to a standardized breakfast in fasting healthy volunteers (n=15). BVM were measured using selected ion flow tube mass spectrometry (SIFT-MS) throughout the day, as well as gastrointestinal tolerance by using validated visual analogue scale. Faecal gut microbiota (Illumina 16S rRNA sequencing) and SCFA (gas chromatography with flame-ionization detection) were analyzed prior to intervention. Results: A single ingestion of 4.5 g CG did not induce significant gastrointestinal discomfort. Untargeted metabolomics analysis of breath highlighted that 13 MS-fragments (among 408 obtained from ionizations of breath) discriminate CG versus maltodextrin acute intake in the postprandial state. Targeted analysis revealed that CG increased exhaled butyrate, but also 5 other BVM – including the microbial metabolites 2,3-butanedione and 3-hydroxybutanone – with a peak observed 6h after CG intake. Correlation analyses spotlighted Mitsuokella as a potential genus responsible for the presence of butyric acid, triethylamine and 3-hydroxybutanone in the breath.Conclusion: Measuring BMV in the breath reveals the microbial signature of the fermentation of DF after a single ingestion. This standardized protocol allows to analyze the time-course of released bioactive metabolites that could be proposed as new biomarkers of DF fermentation, potentially linked to their biological properties.

Background and aims Metabolic and behavioural diseases, which are often related to obesity, have been associated to alterations of the gut microbiota considered as an interesting therapeutic target. We have analyzed in a cohort of obese patients treated with prebiotic inulin versus placebo the potential link between gut microbiota changes occurring upon intervention and their effect on psychological parameters (mood and cognition). Methods A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in 106 obese patients assigned to two groups: prebiotic versus placebo, who received respectively 16 g/d of native inulin or maltodextrin combined with dietary advice to consume inulin-rich or -poor vegetables for 3 months as well as to restrict caloric intake. Anthropometric measurements, food intake, psychological questionnaires, serum measures, and fecal microbiome sequencing were performed before and after the intervention. Results Inulin supplementation in obese subjects had moderate beneficial effect on emotional competence and cognitive flexibility. However, an exploratory analysis revealed that some patients exhibiting specific microbial signature -elevated Coprococcus levels at baseline- were more prone to benefit from prebiotic supplementation in terms of mood. Positive responders toward inulin intervention in term of mood also displayed worse metabolic and inflammatory profiles at baseline (increased levels of IL-8, insulin resistance and adiposity). Conclusion This study shows that inulin intake can be helpful to improve mood in obese subjects exhibiting a specific microbial profile. The present work highlights some microbial, metabolic and inflammatory features (IL-8, insulin resistance) which can predict or mediate the beneficial effects of inulin on behaviour in obesity. Food4gut, clinicaltrial.gov: NCT03852069, https://clinicaltrials.gov/ct2/show/NCT03852069 .

RationaleThe scientific rationale for the recommendation in dietary fiber (DF) intake comes from the recognition of their health benefits. European Food Safety Authority (EFSA) recommend 25 g/d, based on the amount needed for intestinal laxation. Gut microbiota related health benefits are not yet included in the current dietary recommendations. Appropriate (and consensual) quantitative and qualitative analysis of DF are missing in food composition tables. One of the aim of the FiberTAG(1) project was to develop a dedicated database and a food frequency questionnaire (FFQ) allowing DF intake estimation including prebiotic (oligo)saccharides.MethodsA repertoire of DF detailing total, soluble and insoluble DF in food products consumed in Europe has been established based on the Souci-Fachmann-Kraut database, completed for soluble versus insoluble DF () and for prebiotic (oligo)saccharide levels using published data. The FiberTAG FFQ was submitted to healthy volunteers (7 men, 8 women; mean age: 21 yrs; mean BMI: 22kg/m2) and DF intakes were calculated using the new FiberTAG repertoire.ResultsThe FiberTAG repertoire detailed DF in 400 food items allocated into 4 categories (fruits, vegetables, cereal products and others) and 15 subcategories. The fiberTAG FFQ consists in 280 items regrouped in 4 high DF-containing food groups (vegetables including legumes, fruits including nuts and seed, cereal products and others) using frequency scale (6 categories), photographs for portion size and taking into account the seasonal occurrence for some vegetables or fruits. Data obtained from FiberTAG FFQ indicate a total DF intake of 36.44 g/d. This reveals a higher DF intake compared to previously reported intake for adults in Europe ranging from 16 to 24 g/d based on 24 h-recall or 3–7 days records(2). This difference might be explained by a more adequate inclusion of fruits and vegetables intake in FFQ than with other methods, as previously reported(3). Our data also showed that fructan, inulin and fructo-oligosaccharides intakes were 4.18, 2.95 and 1.00 g/day, respectively whereas galacto-oligosaccharides intake was 0.28 g/d.ConclusionThe new FiberTAG DF repertoire and FFQ are tools to evaluate the total amount of DF including prebiotic (oligo)saccharides ingested by healthy volunteers. The FiberTAG project generates scientific knowledge that helps to take into account microbiota-nutrient interactions to establish DF intake recommendations as part of healthy lifestyles.

The scientific rationale for dietary fibre intake recommendations comes from the recognition of their benefits for health based on studies first published many years ago. It remains unclear which are the key physiological effects generated by dietary fibre in view of the diversity of the food components considered as dietary fibre, of the relevance of their classification (soluble and insoluble) and from the recent discoveries putting forward their interactions with the gut microbiota. The project FiberTAG (Joint Programming Initiative ‘A Healthy Diet for a Healthy Life’ 2017–2020 https://www.fibertag.eu/) aims to establish a set of biomarkers (markers of gut barrier function and bacterial co‐metabolites including volatile compounds and lipid derivatives), measured in different biological compartments (faeces, blood or breath) linking dietary fibre intake and gut microbiota‐related health effects. The FiberTAG consortium brings together academic and industrial partners from Belgium, France, Germany and Canada to share data and samples obtained from existing as well as new intervention studies in order to evaluate the relevance of such biomarkers. The FiberTAG consortium is currently working on five existing cohorts (prospective observational or nutritional interventions in healthy or obese patients), and a number of new intervention studies to analyse the effect of insoluble dietary fibre (wheat bran and chitin‐glucan, provided by the industrial partners) in healthy individuals or in obese patients at high cardiometabolic risk.

Alterations of the gut microbiome have been associated with obesity and metabolic disorders. The gut microbiota can be influenced by the intake of dietary fibres with prebiotic properties, such as inulin-type fructans. The present study tested the hypothesis that obese individuals subjected for 12 weeks to an inulin-enriched v. inulin-poor diet have differential faecal fermentation patterns. The fermentation of cellulose and inulin hydrolysates of six different inulin-rich and inulin-poor vegetables of both groups was analysed in vitro on faecal inocula. The results showed that the microbiota from obese patients who received a fructan-rich diet for 3 weeks produces more gas and total SCFA compared with the microbiota taken from the same individuals before the treatment. Obese individuals fed with a low-fructan diet produce less gas and less SCFA compared with the treated group. The present study highlighted profound changes in microbiota fermentation capacity obtained by prebiotic intervention in obese individuals, which favours the production of specific bioactive metabolites.

IntroductionDietary fibers (DF) are considered as beneficial nutrients for health. Current data suggest that their interaction with the gut microbiota largely contributes to their physiological effects. The FiberTAG project(1) innovates in searching for new biomarkers reflecting the health effect of dietary fibers, including chitin-glucan (CG, extracted from the fungal exoskeleton Aspergillus niger). CG improves metabolic disorders associated with obesity in mice, but its effect on gut microbiota composition and function has never been evaluated in vivo in humans.Materials and MethodsCG (KitoZyme, Belgium) was given to healthy volunteers (n = 15), during three weeks (4.5g/day). Volatile Organic Compound (VOC) metabolites released in breath were analyzed using SYFT methodology. Fatty acid (FA) profiling was assessed in stool samples, by gas-liquid chromatography(2). The gut microbiome was analyzed by Illumina sequencing (V5-V6 region of 16S rRNA).ResultsThree weeks of CG supplementation was well tolerated and lead to changes in the kinetics of breath VOC, especially the short-chain fatty acid, alcohols and alkanes. Fecal vaccenic acid, produced upon the bacterial metabolism of fatty acids, was significantly increased by CG. Several bacterial genera were correlated with breath VOC (i.e. 2 methylbutyric acid and RuminococcaceaeUCG005). Moreover, Roseburia, often presented as a butyrate producer, was positively correlated with the production of a rumenic acid isomer “cis-9,cis-11-18:2”.DiscussionWe show that breath VOC analysis, a non-invasive methodology, reveals characteristics of microbiota-CG interactions. We also show that CG selectively changes the profile of FA metabolites, in favor of vaccenic acid, another bioactive metabolite produced by Roseburia, prone to act on host physiology. This study will help to establish a set of new biomarkers linking insoluble DF and gut microbiota, with focus on their interest in human health.

Objectives:We describe the methodology of a trial designed to highlight the interest of vegetables rich in ITF-prebiotics in obese adults. DESIGN:150 obese subjects (BMI> 30 kg.m-2; 18–65 years) recruited in three different university hospitals in Belgium will be selected with at least one of the following criteria: (pre-)diabetes, hypertension, dyslipidemia, liver steatosis. They will be randomly assigned to receive either 16 g/day of inulin (Fibruline, Cosucra) with dietary advice to promote the consumption of vegetables rich in ITF or 16 g/day placebo (maltodextrin, Cargill) with dietary advice provided nutrients to promote the consumption of vegetables poor in ITF for 3 months. Review of literature, analysis of ITF content in vegetables and satisfaction and digestive tolerance tests (on healthy volunteers) will be performed to propose adequate receipts. Results: The primary outcome is to evaluate the impact of a higher consumption of ITF-prebiotics on the gut microbiota composition. The secondary outcome of this trial was the effect of the prebiotic intervention on the BMI. Other secondary endpoints were anthropometric and clinical parameters. Conclusions:The goal of this intervention study is to establish the proof of concept that nutrients which selectively stimulate the growth of beneficial bacteria in the human colon might offer protection against metabolic disorders associated to obesity on an adequate target population.

Background The control of muscle size is an essential feature of health. Indeed, skeletal muscle atrophy leads to reduced strength, poor quality of life, and metabolic disturbances. Consequently, strategies aiming to attenuate muscle wasting and to promote muscle growth during various (pathological) physiological states like sarcopenia, immobilization, malnutrition, or cachexia are needed to address this extensive health issue. In this study, we tested the effects of urolithin B, an ellagitannin-derived metabolite, on skeletal muscle growth. Methods C2C12 myotubes were treated with 15 μM of urolithin B for 24 h. For in vivo experiments, mice were implanted with mini-osmotic pumps delivering continuously 10 μg/day of urolithin B during 28 days. Muscle atrophy was studied in mice with a sciatic nerve denervation receiving urolithin B by the same way. Results Our experiments reveal that urolithin B enhances the growth and differentiation of C2C12 myotubes by increasing protein synthesis and repressing the ubiquitin–proteasome pathway. Genetic and pharmacological arguments support an implication of the androgen receptor. Signalling analyses suggest a crosstalk between the androgen receptor and the mTORC1 pathway, possibly via AMPK. In vivo experiments confirm that urolithin B induces muscle hypertrophy in mice and reduces muscle atrophy after the sciatic nerve section. Conclusions This study highlights the potential usefulness of urolithin B for the treatment of muscle mass loss associated with various (pathological) physiological states.

Resume Ce rapport de cas aborde l’interet de l’echographie pulmonaire en kinesitherapie respiratoire chez une patiente presentant une pneumopathie. L’utilisation de l’echographie pulmonaire dans le processus de decision clinique pourrait aider le kinesitherapeute a choisir avec plus de precision la strategie therapeutique. De plus, elle permet d’evaluer le traitement en temps reel et de controler la reponse du patient. Niveau de preuve 5.

Objetivo: Identificar el uso de fuentes y tecnologías de la información y comunicación según el tipo de universidad en siete países de América Latina. Métodos: Estudio transversal analítico, en estudiantes de medicina de siete países de América Latina. Se midió el uso de fuentes y tecnologías de información y comunicación con el autoreporte sobre el uso de buscadores científicos (SciELO, PubMed, Google Scholar) y TIC (laptop, smarphone, wifi). Las variables secundarias fueron el país y el tipo de universidad de procedencia (pública/privada) de los estudiantes de medicina. Se reportó valores p menores de 0,05 como estadísticamente significativos. Resultados: De 4463 encuestados, SciELO fue usado por el 83,3% y el 55,0% en una universidad pública y privada, respectivamente. Mientras que PubMed fue reportado por el 79,9% y 59,2% de estudiantes de universidad pública y privada, respectivamente. Las universidades privadas tuvieron mayor uso de TIC en Panamá y Bolivia, en contraste con aquellas de tipo públicas fueron Paraguay, México, Colombia y Argentina. La mayoría de los estudiantes usaban smartphone en más del 60%. Conclusión: El smartphone fue utilizado por la mayoría de los estudiantes. El uso de Internet fue mayor en estudiantes de universidades privadas. No se encontraron grandes porcentajes del uso de PubMed y SciELO en universidades públicas y privadas. Se deben reforzar las estrategias educativas en el campo de la educación médica, debido a pobre cultura de manejo de información basada en evidencias.

AB Purpose: To determine whether endurance training attenuates the negative effects induced by an acute injection of tumor necrosis factor-[alpha] (TNF-[alpha]) in skeletal muscle of mice. Methods: Trained (6 wk of endurance training at 60% of maximal velocity) and untrained mice were injected with TNF-[alpha] or vehicle and killed 6 h after. Tibialis anterior muscles were analyzed using Western blot and qRT-PCR for markers of inflammation and protein synthesis/degradation. Results: Independently of training, TNF-[alpha] increased the mRNA of cytokines and downregulated signals linked to protein synthesis. The phosphorylation of IKK[alpha]/[beta] and I[kappa]B[alpha] induced by TNF-[alpha] was blunted in trained mice, suggesting altered NF-[kappa]B activation. This was associated with lower induction of several markers of protein degradation (FoxO1, MURF1, MAFbx, myostatin, Gabarapl1, and LC3BII/LC3BI ratio). Conclusions: Endurance training protects skeletal muscle against the activation of protein degradation signaling pathways induced by TNF-[alpha]

Scope More than a decade ago, the concept of "metabolic endotoxemia" is elaborated on the fact that some bacterial components, classified as microbial associated membrane pathogens (MAMPs) can pass through the gut barrier and create a systemic low tone inflammation. Methods and results The translocation of lipopolysaccharides and its contribution to systemic inflammation are largely studied in murine models of obesity, allowing to unravel the molecular pathways involved in the process. Many different pathological contexts evoke the loss of gut barrier as an event contributing to inflammation and thereby driving metabolic and behavioral alterations. Conclusion This review describes the role of nutrition as a modulator of metabolic regulation and focuses on the contribution of the gut microbiota in the process of the production of a large diversity of bioactive metabolites. The two first sections of the review will be dedicated to the impact of nutritional disorders on both the gut microbiota composition and on metabolic inflammation. The last and more prominent section will describe the role of different nutrient-derived gut metabolites on the gut barrier integrity, metabolic inflammation, and peripheral tissue alterations during obesity or associated complications.

Most official food composition tables and food questionnaires do not provide enough data to assess fermentable dietary fibers (DF) that can exert a health effect through their interaction with the gut microbiota. The aim of this study was to develop a database and a food frequency questionnaire (FFQ) allowing detailed DF intake estimation including prebiotic (oligo)saccharides. A repertoire of DF detailing total, soluble DF, insoluble DF and prebiotic (oligo)saccharides (inulin-type fructans, fructo-oligosaccharides and galacto-oligosaccharides) in food products consumed in Europe has been established. A 12 month FFQ was developed and submitted to 15 healthy volunteers from the FiberTAG study. Our data report a total DF intake of 38 g/day in the tested population. Fructan and fructo-oligosaccharides intake, linked notably to condiments (garlic and onions) ingestion, reached 5 and 2 g/day, respectively, galacto-oligosaccharides intake level being lower (1 g/day). We conclude that the FiberTAG repertoire and FFQ are major tools for the evaluation of the total amount of DF including prebiotics. Their use can be helpful in intervention or observational studies devoted to analyze microbiota&ndash, nutrient interactions in different pathological contexts, as well as to revisit DF intake recommendations as part of healthy lifestyles considering specific DF.

A scanning densitometry-based method was used to determine absolute surface concentrations and homogeneity of a spray-coating treatment with a model dye, 5,8-dihydroxy-[1,4]-naphthoquinone (DHNQ), on hardwood veneers (Beech, Fagus sylvatica; Birch, Betula pendula; Oak, Quercus alba). An automatic TLC sampler sprayed accurately known amounts of several concentrations of DHNQ as rectangles on the surface. Scanning was then used to acquire the color intensities of each rectangle. After an adequate data treatment, three models – Michaelis-Menten and two logarithmic – were selected to fit the obtained intensities to the deposited surface concentrations. Based on the quality of fit and the residuals, the logarithmic model is examined in detail in this work. The method was validated by comparing expected concentrations to back-calculated ones, and produced correct results with acceptable error within ±20%. The applicability of the method was shown by a sprayed specimen. By comparing our method to two widely applied techniques, CIELAB color system and x-ray fluorescence, we demonstrated that densitometry is advantageous as it measures an absolute surface concentration, also of coatings containing atoms lighter than silicon. In production, densitometry can be adapted from current technologies and would quickly control the quality of the coated wood, or any other surface, with good sensitivity.

Background: Inulin-Type fructans (ITFs) are a type of fermentable dietary fiber that can confer beneficial health effects through changes in the gut microbiota. However, their effect on gut sensitivity and nutritional behavior is a matter of debate. Objective: We evaluated the impact of consuming ITF-rich vegetables daily on gut microbiota, gastro-intestinal symptoms, and foodrelated behavior in healthy individuals. Methods: A single group-design trial was conducted in 26 healthy individuals. During 2 wk, the participants were instructed to adhere to a controlled diet based on ITF-rich vegetables (providing a mean intake of 15 g ITF/d). Three test days were organized: before and after the nutritional intervention and 3 wk after returning to their usual diet. We assessed nutrient intake, food-related behavior, fecal microbiota composition, microbial fermentation, and gastrointestinal symptoms. Results: The major microbial modifications during the intervention were an increased proportion of the Bifidobacterium genus, a decreased level of unclassified Clostridiales, and a tendency to decrease Oxalobacteraceae. These changes were reversed 3 wk after the intervention. The volunteers showed greater satiety, a reduced desire to eat sweet, salty, and fatty food, and a trend to increase hedonic attitudes towards some inulin-rich vegetables. Only flatulence episodes were reported during the dietary intervention, whereas intestinal discomfort, inversely associated with Clostridium cluster IV and Ruminococcus callidus, was improved at the end of the intervention. Conclusions: A higher consumption of ITF-rich vegetables allows a substantial increase in well-Tolerated dietary fiber, which may in turn improve food-related behavior. Moreover, it leads to beneficial modifications of the gut microbiota composition and function. This trial is registered at clinicaltrial.gov as NCT03540550., SCOPUS: ar.j, info:eu-repo/semantics/published

The gut microbiota regulates key hepatic functions, notably through the production of bacterial metabolites that are transported via the portal circulation. We evaluated the effects of metabolites produced by the gut microbiota from aromatic amino acids (phenylacetate, benzoate, p-cresol, and indole) on liver inflammation induced by bacterial endotoxin. Precision-cut liver slices prepared from control mice, Kupffer cell (KC)-depleted mice, and obese mice ( ob/ ob) were treated with or without LPS and bacterial metabolites. We observed beneficial effects of indole that dose-dependently reduced the LPS-induced up-regulation of proinflammatory mediators at both mRNA and protein levels in precision-cut liver slices prepared from control or ob/ ob mice. KC depletion partly prevented the antiinflammatory effects of indole, notably through a reduction of nucleotide-binding domain and leucine-rich repeat containing (NLR) family pyrin domain-containing 3 (NLRP3) pathway activation. In vivo, the oral administration of indole before an LPS injection reduced the expression of key proteins of the NF-κB pathway and downstream proinflammatory gene up-regulation. Indole also prevented LPS-induced alterations of cholesterol metabolism through a transcriptional regulation associated with increased 4β-hydroxycholesterol hepatic levels. In summary, indole appears as a bacterial metabolite produced from tryptophan that is able to counteract the detrimental effects of LPS in the liver. Indole could be a new target to develop innovative strategies to decrease hepatic inflammation.-Beaumont, M., Neyrinck, A. M., Olivares, M., Rodriguez, J., de Rocca Serra, A., Roumain, M., Bindels, L. B., Cani, P. D., Evenepoel, P., Muccioli, G. G., Demoulin, J.-B., Delzenne, N. M. The gut microbiota metabolite indole alleviates liver inflammation in mice. ispartof: FASEB JOURNAL vol:32 issue:12 pages:6681-6693 ispartof: location:United States status: published

Gut dysbiosis was recently associated with the occurrence of type 2 diabetes (T2D). In addition to this finding, an increasing number of studies performed upon the last 5 years have also shown that metformin treatment leads to changes in gut bacterial composition in diabetic patients. This review focuses on the articles describing the effects of metformin on gut homeostasis (including the gut microbiota) and proposes potential mechanisms involved in those effects.Several human and animal studies emphasized that metformin alters the gut microbiota composition by enhancing the growth of some bacteria, such as Akkermansia muciniphila, Escherichia spp. or Lactobacillus and by decreasing the levels of some other ones like Intestinibacter. In-vitro studies also demonstrated a direct action of metformin on the growth of A. muciniphila and Bifidobacterium adolescentis. Moreover, in the intestines, metformin does not only improve the glucose uptake, but it also promotes the short-chain fatty acid (SCFA) production, protects the intestinal barrier and regulates the secretion of gut peptides SUMMARY: It is now clear that gut microbiota participates to the glucose-lowering effects of metformin in the context of diabetes. Further work is now needed to determine the exact mechanisms of action of the drug and to understand by which processes metformin is able to enhance the growth of some bacteria exhibiting beneficial effects for the host.

Postprandial hyperlipidemia is an important risk factor for cardiovascular diseases in the context of obesity. Inulin is a non-digestible carbohydrate, known for its beneficial properties in metabolic disorders. We investigated the impact of inulin on postprandial hypertriglyceridemia and on lipid metabolism in a mouse model of diet-induced obesity. Mice received a control or a western diet for 4 weeks and were further supplemented or not with inulin for 2 weeks (0.2 g/day per mouse). We performed a lipid tolerance test, measured mRNA expression of genes involved in postprandial lipid metabolism, assessed post-heparin plasma and muscle lipoprotein lipase activity and measured lipid accumulation in the enterocytes and fecal lipid excretion. Inulin supplementation in western diet-fed mice decreases postprandial serum triglycerides concentration, decreases the mRNA expression levels of Cd36 (fatty acid receptor involved in lipid uptake and sensing) and apolipoprotein C3 (Apoc3, inhibitor of lipoprotein lipase) in the jejunum and increases fecal lipid excretion. In conclusion, inulin improves postprandial hypertriglyceridemia by targeting intestinal lipid metabolism. This work confirms the interest of using inulin supplementation in the management of dyslipidemia linked to obesity and cardiometabolic risk.