Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology

Objective: Individuals with obesity and type 2 diabetes differ from lean and healthy individuals in their abundance of certain gut microbial species and microbial gene richness. Abundance of Akkermansia muciniphila, a mucin-degrading bacterium, has been inversely associated with bodyfat mass and glucose intolerance in mice, but more evidence is needed in humans. The impact of diet and weight loss on this bacterial species is unknown. Our objective was to evaluate the association between fecal A. muciniphila abundance, fecal microbiome gene richness, diet, host characteristics, and their changes after calorie restriction (CR). Design: The intervention consisted of a 6-week CR period followed by a 6-week weight stabilization (WS) diet in overweight and obese adults (N=49, including 41 women). Fecal A. muciniphila abundance, fecal microbial gene richness, diet and bioclinical parameters were measured at baseline and after CR and WS. Results: At baseline A. muciniphila was inversely related to fasting glucose, waist-to-hip ratio, and subcutaneous adipocyte diameter. Subjects with higher gene richness and A. muciniphila abundance exhibited the healthiest metabolic status, particularly in fasting plasma glucose, plasma triglycerides and body fat distribution. Individuals with higher baseline A. muciniphila displayed greater improvement in insulin sensitivity markers and other clinical parameters after CR. A. muciniphila was associated with microbial species known to be related to health. Conclusion: A. muciniphila is associated with a healthier metabolic status and better clinicaloutcomes after CR in overweight/obese adults, however the interaction between gut microbiota ecology and A. muciniphila has to be taken into account

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\u27s 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

Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk

Facteurs prédictifs de plaies podologiques et d'amputations chez les diabétiques de type 1 après la greffe rein-pancréas

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Fecal Microbiota Transplantation: a Future Therapeutic Option for Obesity/Diabetes?

Purpose of Review: The aim of this review is to summarize the current data available on the metabolic effects of fecal microbiota transplantation (FMT) including obesity and glucose metabolism in humans. Recent Findings: Gut microbiota dysbiosis is a frequent characteristic observed in obesity and related metabolic diseases. Pieces of evidence mostly generated in mouse models suggest that rescuing this dysbiosis associates with improved metabolism. In humans, dietary or bariatric surgery interventions are often accompanied by complete or partial restoration of this dysbiosis together with weight reduction and metabolic amelioration. FMT is an interesting option to modify gut microbiota and has been associated with improved clinical outcomes, albeit only used in routine care for Clostridium difficile infection. However, there are only limited data on using FMT in the metabolic context. Summary: FMT from lean donors significantly improves insulin sensitivity in obese subjects with metabolic syndrome. However, there is a wide range of clinical responses. Interestingly in subjects with high microbial gene richness at baseline and when FMT donors that are metabolically compromised are used, no metabolic improvement is seen. Moreover, more studies evaluating the effect of FMT in patients with overt type 2 diabetes are warranted. Furthermore, interventions (in the receiver prior to FMT) aiming to enhance FMT response also need evaluation

Fecal Microbiota Transplantation: a Future Therapeutic Option for Obesity/Diabetes?

Purpose of Review: The aim of this review is to summarize the current data available on the metabolic effects of fecal microbiota transplantation (FMT) including obesity and glucose metabolism in humans. Recent Findings: Gut microbiota dysbiosis is a frequent characteristic observed in obesity and related metabolic diseases. Pieces of evidence mostly generated in mouse models suggest that rescuing this dysbiosis associates with improved metabolism. In humans, dietary or bariatric surgery interventions are often accompanied by complete or partial restoration of this dysbiosis together with weight reduction and metabolic amelioration. FMT is an interesting option to modify gut microbiota and has been associated with improved clinical outcomes, albeit only used in routine care for Clostridium difficile infection. However, there are only limited data on using FMT in the metabolic context. Summary: FMT from lean donors significantly improves insulin sensitivity in obese subjects with metabolic syndrome. However, there is a wide range of clinical responses. Interestingly in subjects with high microbial gene richness at baseline and when FMT donors that are metabolically compromised are used, no metabolic improvement is seen. Moreover, more studies evaluating the effect of FMT in patients with overt type 2 diabetes are warranted. Furthermore, interventions (in the receiver prior to FMT) aiming to enhance FMT response also need evaluation

Le transfert de microbiote fécal : quel potentiel thérapeutique dans le traitement des maladies métaboliques ?

International audienceAn imbalance of the gut microbiota composition or functions is frequently observed during obesity and metabolic diseases. Studies on rodents showed that the modulation of microbiota dysbiosis by various methods is associated with an improvement in metabolic parameters. In humans, dietary interventions or bariatric surgery are accompanied by changes in the composition of the microbiota. Fecal microbiota transfer is a promising therapeutic approach to change the composition of the gut microbiota, however, it is currently only officially indicated in the treatment of recurrent Clostridioides difficile colitis. Literature documenting the effect of faecal microbiota transplantation in metabolic diseases is much less abundant. Nevertheless, FMT from healthy donors to obese patients with metabolic syndrome significantly improves the insulin sensitivity of the recipients despite the large response variability. This variability seems to be mainly related to the difference in richness between the donor's microbiota and the recipient's microbiota. To date, the impact of the donor's choice, the protocol of preparation, storage and administration of the inoculum, as well as the possible preparation of the recipient are to be explored.Un déséquilibre de la composition du microbiote intestinal ou de ses fonctions est fréquemment observé en cas d’obésité et de maladie métabolique. De nombreuses études sur modèle murin montrent que la modification de la dysbiose du microbiote par diverses méthodes est associée à une amélioration des paramètres métaboliques. Chez l’homme, des interventions diététiques ou la chirurgie bariatrique sont accompagnées de modifications plus ou moins importantes de la composition du microbiote. La transplantation de microbiote fécal (TMF) est une option pleine de potentiel pour modifier la composition de ce microbiote intestinal, néanmoins, elle n’est pour le moment officiellement indiquée que dans le traitement des colites récurrentes à Clostridioides difficile. La littérature documentant l’effet du transfert de microbiote fécal dans les maladies métaboliques est en effet beaucoup moins abondante et réalisée sur des petits effectifs. Il a toutefois été montré que la TMF de donneurs sains à des patients obèses souffrant de syndrome métabolique améliorait leur sensibilité à l’insuline de manière significative en dépit de la grande variabilité de réponse. Cette variabilité semble en grande partie dépendante de la différence de richesse entre le microbiote du donneur et celui du receveur. À ce jour, l’impact du choix du donneur, du protocole de préparation, de conservation et d’administration de l’inoculum, ainsi que de l’éventuelle préparation du receveur sont à explorer

Gut Microbiota Dysbiosis in Human Obesity: Impact of Bariatric Surgery

International audiencePURPOSE OF REVIEW: In this review, we summarize what is currently described in terms of gut microbiota (GM) dysbiosis modification post-bariatric surgery (BS) and their link with BS-induced clinical improvement. We also discuss how the major inter-individual variability in terms of GM changes could impact the clinical improvements seen in patients.RECENT FINDINGS: The persisting increase in severe obesity prevalence has led to the subsequent burst in BS number. Indeed, it is to date the best treatment option to induce major and sustainable weight loss and metabolic improvement in these patients. During obesity, the gut microbiota displays distinctive features such as low microbial gene richness and compositional and functional alterations (termed dysbiosis) which have been associated with low-grade inflammation, increased body weight and fat mass, as well as type-2 diabetes. Interestingly, GM changes post-BS is currently being proposed as one the many mechanism explaining BS beneficial clinical outcomes.Summary: BS enables partial rescue of GM dysbiosis observed during obesity. Some of the GM characteristics modified post-BS (composition in terms of bacteria and functions) are linked to BS beneficial outcomes such as weight loss or metabolic improvements. Nevertheless, the changes in GM post-BS display major variability from one patient to the other. As such, further large sample size studies associated with GM transfer studies in animals are still needed to completely decipher the role of GM in the clinical improvements observed post-surgery