Adaptation of Human Gut Microbiota to Energetic Restriction (microbaria)

Modification of Human Gut Microbiota in Massive Obesity After Bariatric Surgery: the Role of Energetic Restriction

Gut microbiota ecology is altered in obesity and could link obesity and its complications. Bariatric surgery enables a major and sustained weight loss therefore improving obesity related disease. the investigators primary aim is to evaluate gut microbiota adaptation to weight loss and the specific role of energetic restriction. Furthermore we aim to compare gut flora of obese patients post bariatric surgery to that of lean healthy volunteers. Thus, the investigators plan to compare gut microbiota from 140 obese individuals before and after either restrictive (gastric banding) procedures or gastric bypass procedures to that of 40 lean healthy volunteers at baseline.

The prevalence of obesity is rising to an epidemic level. Yet medical and pharmacological treatments have proven their limits. Dietetic modifications contribute to adipose tissue alterations and cross talk dysfunction with other tissues linked to weight maintenance. In a previous study in a model of abrupt weight loss 6 months after Roux-en-Y Bypass, the investigators observed a rapid adaptation of the dominant gut microbiota. Conversely some species were directly linked to the improvement of low grade inflammation independently of calory intake. Therefore the investigators hypothesized that gut microbiota in obese patients could link food consumption with obesity alterations such as metabolic impairments, energetic storage dysfunction and increased systemic and adipose tissue inflammation. The investigators want to address the specific role of energetic restriction in gut microbiota modification after weight loss. To answer that question the investigators will evaluate gut microbiota composition before and during the first year after either gastric banding or gastric bypass surgery. they also aim to evaluate whether gut flora post surgery evolves toward that of lean healthy subjects Our study has several objectives. The investigators also aim to assess whether gut microbiota modification is associated with systemic and tissue inflammation reduction and metabolic improvement during the follow up. This project is based on a clinical protocol performed in massively obese subjects (BMI>40 kg/m²). The investigators plan to recruit 70 obese patients addressed for gastric banding and 70 candidates for gastric bypass. Clinical phenotype, biochemical analysis, body composition, systemic and adipose tissue inflammation, endotoxemia and gut microbiota will be assessed at baseline and 1, 3 and 12 months after surgery. Specific food consumption will be recorded at every time point. A group of 40 lean healthy volunteers will undergo the same phenotyping. Associations between all these clinical and biological parameters will be assessed at the different point of the follow up. More generally, this project might lead us to elucidate a new function of gut microbiota and eventually consider novels anti obesity therapeutic strategies

Obesity, adipose tissue inflammation, Low grade systemic inflammation, gut microbiota, Bariatric surgery

Analyse changes early, medium and long term changes in gut microbiota composition in a kinetic manner

Establish early, medium and long term changes in insulin sensitivity and GLP1 secretion profile after oral glucose load and look for potential associations between these changes and gut microbiota composition

Establish early, medium and long term changes in systemic and adipose tissue inflammation and look for potential associations between gut microbiota composition and inflammation modification

Establish early, medium and long term changes in body composition and look for potential associations between these changes and gut microbiota modifications

Establish early, medium and long term changes in nutritional blood sample concentrations and look for a potential association between gut microbiota modifications.

Establish early, medium and long term improvement in obesity related disease (reducing the number of treatments and the need for PPC use) and look for potential association with gut microbiota modification

Obese group Inclusion criteria : Obesity with BMI> 40 kg/m² or obesity with BMI between 35 and 40 kg/M² with comorbidities (OSA, type 2 diabetes, hypertension etc…) Age: 18-65 women weight stable for three months preceding surgery Exclusion criteria : Inflammatory disease Pregnancy Lactose intolerance Antibiotherapy in the three months preceding surgery cancer Drugs (AINS) Healthy group Inclusion criteria : 19<BMI<25kg/m² Age: 18-65 women non diabetic Exclusion criteria : Inflammatory disease Pregnancy Antibiotherapy in the two months preceding the visit pregnancy Drugs (AINS) in the 48h preceding the visit

Aron-Wisnewsky J, Prifti E, Belda E, Ichou F, Kayser BD, Dao MC, Verger EO, Hedjazi L, Bouillot JL, Chevallier JM, Pons N, Le Chatelier E, Levenez F, Ehrlich SD, Dore J, Zucker JD, Clement K. Major microbiota dysbiosis in severe obesity: fate after bariatric surgery. Gut. 2019 Jan;68(1):70-82. doi: 10.1136/gutjnl-2018-316103. Epub 2018 Jun 13.