Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism.

OBJECTIVES: Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome's functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation. DESIGN: We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice. RESULTS: Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration. CONCLUSION: Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity. TRIAL REGISTRATION NUMBER: NCT02059538.

Nonalcoholic Fatty Liver Disease: Modulating Gut Microbiota to Improve Severity?

Gut microbiota plays a role in the pathophysiology of metabolic diseases, which include nonalcoholic fatty liver diseases, through the gut-liver axis. To date, clinical guidelines recommend a weight loss goal of 7%-10% to improve features of nonalcoholic fatty liver diseases. Because this target is not easily achieved by all patients, alternative therapeutic options are currently being evaluated. This review focuses on therapeutics that aim to modulate the gut microbiota and the gut-liver axis. We discuss how probiotics, prebiotics, synbiotic, fecal microbiota transfer, polyphenols, specific diets, and exercise interventions have been found to modify gut microbiota signatures; improve nonalcoholic fatty liver disease outcomes; and detail, when available, the different mechanisms by which these beneficial outcomes might occur. Apart from probiotics that have already been tested in human randomized controlled trials, most of these potential therapeutics have been studied in animals. Their efficacy still warrants confirmation in humans using appropriate design.

A place for vitamin supplementation and functional food in bariatric surgery?

PURPOSE OF REVIEW: This article summarizes recent literature concerning vitamin deficiency and required supplementation post-bariatric surgery, focusing on vitamin D (and associated clinical adverse effect on bone loss) and on the potential implication of the gut microbiota. RECENT FINDINGS: Bariatric surgery induces weight loss and metabolic improvements yet with major inter-individual variability. If it is efficient in most patients, some display poor response (i.e. patients with the lowest weight loss at 1 year or weight regain afterwards, or patients without metabolic disease remission). Despite systematic vitamin supplementation, some patients develop vitamin deficiencies leading to poor clinical outcomes, among which vitamin D deficiency associated with observed bone mass loss and fractures. Recent mechanistic studies led to understand better the involved physiopathology. Furthermore, different intervention studies tested on top of bariatric surgery (using vitamin, diet, or nutrients acting as functional food) have evaluated whether nutritional adverse outcomes could be improved. Importantly, gut microbiota involved in food digestion and metabolization and vitamin synthesis is largely perturbed during severe obesity and is partially restored post-surgery, yet again with large interindividual variability. Whether differential gut microbiota modification could be associated with vitamin deficiencies is an open question. SUMMARY: Future clinical research studies will need to evaluate whether add-on intervention to bariatric surgery using vitamin, diet, or specific food items could help prevent nutritional deficiencies and improve clinical response observed post-surgery. Importantly, personalizing the add-on intervention post-surgery upon gut microbiota composition should be tested in predicted poor-responders to surgery as already performed during diet intervention to further improve metabolic health.

Dietary Assessment in the MetaCardis Study: Development and Relative Validity of an Online Food Frequency Questionnaire.

BACKGROUND: The European study MetaCardis aims to investigate the role of the gut microbiota in health and cardiometabolic diseases in France, Germany, and Denmark. To evaluate long-term diet-disease relationships, a food frequency questionnaire (FFQ) was found to be the most relevant dietary assessment method for the MetaCardis study. OBJECTIVE: The objectives of this study were to describe the development of three semiquantitative online FFQs used in the MetaCardis study-one FFQ per country-and to assess the relative validity of the French MetaCardis FFQ. DESIGN: The layout and format of the MetaCardis FFQ was based on the European Prospective Investigation of Cancer (EPIC)-Norfolk FFQ and the content was based on relevant European FFQs. Portion size and nutrient composition were derived from national food consumption surveys and food composition databases. To assess the validity of the French MetaCardis FFQ, a cross-sectional study design was utilized. PARTICIPANTS/SETTING: The validation study included 324 adults recruited between September 2013 and June 2015 from different hospitals in Paris, France. MAIN OUTCOME MEASURES: Food intakes were measured with both the French MetaCardis FFQ and 3 consecutive self-administered web-based 24-hour dietary recalls (DRs). STATISTICAL ANALYSES PERFORMED: Several measures of validity of the French MetaCardis FFQ were evaluated: estimations of food groups, energy, and nutrient intakes from the DRs and the FFQ, Spearman and Pearson correlations, cross-classification, and Bland-Altman analyses. RESULTS: The French MetaCardis FFQ tended to report higher food, energy, and nutrient intakes compared with the DRs. Mean correlation coefficient was 0.429 for food, 0.460 for energy, 0.544 for macronutrients, 0.640 for alcohol, and 0.503 for micronutrient intakes. Almost half of participants (44.4%) were correctly classified within tertiles of consumption, whereas 12.9% were misclassified in the opposite tertile. Performance of the FFQ was relatively similar after stratification by sex. CONCLUSIONS: The French MetaCardis FFQ was found to have an acceptable level of validity and may be a useful instrument to rank individuals based on their food and nutrient intakes.

Nutritional and Protein Deficiencies in the Short Term following Both Gastric Bypass and Gastric Banding.

BACKGROUND: The number of morbidly obese patients undergoing bariatric surgery (BS) has increased dramatically in recent years. Therefore, monitoring food intake and its consequences in terms of nutritional status is necessary to prevent nutritional deficiencies. The aim of this study was to analyze the effect of food restriction on nutritional parameters in the short-term (≤3 months) period after BS in morbid obesity. METHOD: In a prospective study, we followed 22 obese women who underwent Roux-en-Y gastric bypass (GBP) or adjustable gastric banding (AGB) at baseline (T0) and 1 (T1) and 3 (T3) months after surgery. We evaluated food intake, nutrient adequacy and serum concentrations of vitamins and minerals known to be at risk for deficiency following BS. RESULTS: Before surgery, we observed suboptimal food intakes, leading to a risk of micronutrient deficiencies. Serum analysis confirmed nutritional deficiencies for iron and thiamine for 27 and 23% of the patients, respectively. The drastic energy and food reduction seen in the short term led to very low probabilities of adequacy for nutrients equivalent across both surgeries. Serum analysis demonstrated a continuous decrease in prealbumin during the follow-up, indicating mild protein depletion in 21 and 57% of GBP patients and 50 and 63% of AGB patients, respectively, at T1 and T3. Regarding vitamins and minerals, systematic supplementation after GBP prevented most nutritional deficiencies. By contrast, AGB patients, for whom there is no systematic supplementation, developed such deficiencies. CONCLUSIONS: Our results suggest that cautious monitoring of protein intake after BS is mandatory. Furthermore, AGB patients might also benefit from systematic multivitamin and mineral supplementation at least in the short term.

Micronutrient and Protein Deficiencies After Gastric Bypass and Sleeve Gastrectomy: a 1-year Follow-up.

BACKGROUND: Roux-en-Y gastric bypass (GBP) and sleeve gastrectomy (SG) have increased dramatically, potentially increasing the prevalence of nutritional deficiencies. The aim of this study was to analyze the effects of food restriction during the first year after bariatric surgery (BS) on nutritional parameters. METHODS: Twenty-two and 30 obese patients undergoing GBP and SG were prospectively followed at baseline and 3, 6, and 12 months after BS (N = 14 and N = 19 at T12). We evaluated food intake and nutrient adequacy (T0, T3, T12), as well as serum vitamin and mineral concentration (T0, T3, T6, T12). RESULTS: At baseline, GBP and SG patients had similar clinical characteristics, food intake, nutrient adequacy, and serum concentration. The drastic energy and food reduction led to very low probabilities of adequacy for nutrients similar in both models (T3, T12). Serum analysis demonstrated a continuous decrease in prealbumin during the follow-up, indicating mild protein depletion in 37 and 38% of GBP patients and 57 and 52% of SG patients, respectively, at T3 and T12. Conversely, despite the low probabilities of adequacy observed at T3 and T12, systematic multivitamin and mineral supplementation after GBP and SG prevented most nutritional deficiencies. CONCLUSIONS: GBP and SG have comparable effects in terms of energy and food restriction and subsequent risk of micronutrient and protein deficiencies in the first year post BS. Such results advocate for a cautious monitoring of protein intake after GPB and SG and a systematic multivitamin and mineral supplementation in the first year after SG.