Elucidating the role of the gut microbiota in the physiological effects of dietary fiber.

BACKGROUND: Dietary fiber is an integral part of a healthy diet, but questions remain about the mechanisms that underlie effects and the causal contributions of the gut microbiota. Here, we performed a 6-week exploratory trial in adults with excess weight (BMI: 25-35 kg/m2) to compare the effects of a high-dose (females: 25 g/day; males: 35 g/day) supplement of fermentable corn bran arabinoxylan (AX; n = 15) with that of microbiota-non-accessible microcrystalline cellulose (MCC; n = 16). Obesity-related surrogate endpoints and biomarkers of host-microbiome interactions implicated in the pathophysiology of obesity (trimethylamine N-oxide, gut hormones, cytokines, and measures of intestinal barrier integrity) were assessed. We then determined whether clinical outcomes could be predicted by fecal microbiota features or mechanistic biomarkers. RESULTS: AX enhanced satiety after a meal and decreased homeostatic model assessment of insulin resistance (HOMA-IR), while MCC reduced tumor necrosis factor-α and fecal calprotectin. Machine learning models determined that effects on satiety could be predicted by fecal bacterial taxa that utilized AX, as identified by bioorthogonal non-canonical amino acid tagging. Reductions in HOMA-IR and calprotectin were associated with shifts in fecal bile acids, but correlations were negative, suggesting that the benefits of fiber may not be mediated by their effects on bile acid pools. Biomarkers of host-microbiome interactions often linked to bacterial metabolites derived from fiber fermentation (short-chain fatty acids) were not affected by AX supplementation when compared to non-accessible MCC. CONCLUSION: This study demonstrates the efficacy of purified dietary fibers when used as supplements and suggests that satietogenic effects of AX may be linked to bacterial taxa that ferment the fiber or utilize breakdown products. Other effects are likely microbiome independent. The findings provide a basis for fiber-type specific therapeutic applications and their personalization. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02322112 , registered on July 3, 2015. Video Abstract.

Chitin-glucan supplementation improved postprandial metabolism and altered gut microbiota in subjects at cardiometabolic risk in a randomized trial.

Chitin-glucan (CG), an insoluble dietary fiber, has been shown to improve cardiometabolic disorders associated with obesity in mice. Its effects in healthy subjects has recently been studied, revealing its interaction with the gut microbiota. In this double-blind, randomized, cross-over, twice 3-week exploratory study, we investigated the impacts of CG on the cardiometabolic profile and gut microbiota composition and functions in 15 subjects at cardiometabolic risk. They consumed as a supplement 4.5 g of CG daily or maltodextrin as control. Before and after interventions, fasting and postprandial metabolic parameters and exhaled gases (hydrogen [H2] and methane [CH4]) were evaluated. Gut microbiota composition (16S rRNA gene sequencing analysis), fecal concentrations of bile acids, long- and short-chain fatty acids (LCFA, SCFA), zonulin, calprotectin and lipopolysaccharide binding protein (LBP) were analyzed. Compared to control, CG supplementation increased exhaled H2 following an enriched-fiber breakfast ingestion and decreased postprandial glycemia and triglyceridemia response to a standardized test meal challenge served at lunch. Of note, the decrease in postprandial glycemia was only observed in subjects with higher exhaled H2, assessed upon lactulose breath test performed at inclusion. CG decreased a family belonging to Actinobacteria phylum and increased 3 bacterial taxa: Erysipelotrichaceae UCG.003, Ruminococcaceae UCG.005 and Eubacterium ventriosum group. Fecal metabolites, inflammatory and intestinal permeability markers did not differ between groups. In conclusion, we showed that CG supplementation modified the gut microbiota composition and improved postprandial glycemic response, an early determinant of cardiometabolic risk. Our results also suggest breath H2 production as a non-invasive parameter of interest for predicting the effectiveness of dietary fiber intervention.

Effect of an intensified individual nutrition therapy on serum metabolites in critically ill patients - A targeted metabolomics analysis of the ONCA study.

PURPOSE: The effect of medical nutrition on serum metabolomics has been poorly explored. The aim of the study was to investigate the relation between energy supply and metabolic profiles in critically ill patients. MATERIALS AND METHODS: Twenty mechanically ventilated patients on enteral nutrition (EN) or enteral/parenteral nutrition (EN/PN) were randomized into two groups. One group received an individual energy supply based on indirect calorimetry (IC group, n = 9), the other group received a standard energy supply based on a formula, the standard care group (SC group, n = 11). Targeted metabolomics was performed in early-, late- and post-acute metabolic phase. RESULTS: Individual versus standard care energy supply resulted in a metabolite class separation between the IC and the SC group (P < 0.001). In the SC group concentrations of four glucogenic amino acids and three biogenic amines increased between the early- and late-acute metabolic phase (P < 0.05). The metabolomics pattern differed between the routes of nutrition administration (P < 0.01). CONCLUSIONS: The amount of energy supply by EN or PN, besides other factors, seems to modulate serum metabolites. Nutrition therapy based on individualized energy supply is associated with a reduction of metabolites reflecting catabolism. Therefore, metabolomics could be a new tool to determine metabolic phases in critically ill patients.

Metabolite profiling reveals the interaction of chitin-glucan with the gut microbiota.

Dietary fibers are considered beneficial nutrients for health. Current data suggest that their interaction with the gut microbiota largely contributes to their physiological effects. In this context, chitin-glucan (CG) improves metabolic disorders associated with obesity in mice, but its effect on gut microbiota has never been evaluated in humans. This study explores the effect of a 3-week intervention with CG supplementation in healthy individuals on gut microbiota composition and bacterial metabolites. CG was given to healthy volunteers (n = 15) for three weeks as a supplement (4.5 g/day). Food diary, visual analog and Bristol stool form scales and a "quality of life" survey were analyzed. Among gut microbiota-derived metabolites, bile acids (BA), long- and short-chain fatty acids (LCFA, SCFA) profiling were assessed in stool samples. The gut microbiota (primary outcome) was analyzed by Illumina sequencing. A 3-week supplementation with CG is well tolerated in healthy humans. CG induces specific changes in the gut microbiota composition, with Eubacterium, Dorea and Roseburia genera showing the strongest regulation. In addition, CG increased bacterial metabolites in feces including butyric, iso-valeric, caproic and vaccenic acids. No major changes were observed for the fecal BA profile following CG intervention. In summary, our work reveals new potential bacterial genera and gut microbiota-derived metabolites characterizing the interaction between an insoluble dietary fiber -CG- and the gut microbiota.

Fatty acid profiles in erythrocyte membranes following the Mediterranean diet - data from a multicenter lifestyle intervention study in women with hereditary breast cancer (LIBRE).

BACKGROUND & AIMS: Evidence-based concepts to prevent breast cancer in women with BRCA1/2 mutations are limited. Adherence to a Mediterranean diet (MedD) has been associated with a lower risk for breast cancer, possibly due to a favorable fatty acid (FA) intake. Here, we studied in an at-risk population the effect of a lifestyle intervention that included the MedD on FA composition in red blood cell membranes (RBCM). METHODS: Data derived from the German multicenter trial LIBRE, from which 68 women were randomized into an intervention group (IG) trained for MedD and increased physical activity for 12 months, and a usual care control group (CG). Adherence to the diet was assessed after 3 and 12 months using the validated Mediterranean Diet Adherence Screener (MEDAS) and a food frequency questionnaire. RBCM FA were analyzed by gas chromatography with mass spectrometry. RESULTS: The MEDAS was increased in both groups after 3 months (IG: P < 0.001; CG: P = 0.004), and remained increased only in the IG after 12 months (P < 0.001). The food frequency questionnaire revealed an increased intake of omega-3 (n-3) FA at month 3 and month 12 in the IG (both P < 0.01), but not in the CG, in which intake of energy, protein and saturated FA decreased. In both groups n-6 FA in the RBCM decreased (P < 0.001), while n-9 FA increased (P < 0.001) and n-3 FA were unchanged. Women with higher consumption of fish had higher amounts of n-3 fatty acids in the RBCM. The MEDAS was inversely correlated with n-6 fatty acids. CONCLUSIONS: The RBCM FA composition was associated with dietetic parameters related to the MedD. Adherence to the MedD resulted in an altered, likely favorable FA composition. Our data suggest selected FA as biomarkers to monitor compliance to a dietetic intervention such as the MedD. CLINICAL TRIAL REGISTRY: The trial is registered at ClinicalTrials.gov (reference: NCT02087592).