Human Intestinal Microbiota in Obesity and Nutritional Transition

Obesity

obesity, low calorie diet, intestinal microbiota, inflammation (systemic and in adipose tissue), fat mass, Impact of nutritional transition on intestinal microbiota, relation between food intake, clinical parameters and intestinal microbiota

The objectives of this study are: 1-To qualify the relationship between the gut microbiota and the host nutritional and metabolic status during dietary transition.2-To define the impact of nutritional transition on the intestinal microbiota and identify metagenomics signatures of nutritional transition.

French overweight (BMI \> 27) and obese people (BMI \> 30 kg/m2, N=50) will be submitted to a low calorie diet (1200 Kcal) for 8 weeks. This type of intervention is know to modify the metabolic phenotype and expected to change the gut microbiota. Nutritional interventions are planned for 6 months, each subject being studied before (base line), after the intervention (8 weeks) and 2 months after the low calorie diet has stopped and a diet of weight maintenance will be provided. This protocol will be implemented in the nutrition department of the Pitié Salpétrière Hospital in Paris, within the Centre de Recherche en Nutrition Humaine d'Ile-de-France, where patients will be followed on the clinical, biological and histological levels. Evaluation will include medical history, physical, and nutritional evaluations. They will be excluded of the protocol if they had evidence of acute or chronic inflammatory disease, infectious diseases, cancer and/or known alcohol consumption (\> 20g per day), as well as other causes of liver, kidney or heart diseases. Physical evaluation will include weight, height, measures of waist/hip ratio, measure of blood pressure. At each time point, body composition will be measured by dual-energy X-ray absorptiometry performed with a total body scanner (Hologic QDR 2500 densitometer). Resting metabolic rate will be evaluated after a one-hour resting period in supine position. Oxygen consumption (VO2) and carbon dioxide production (VCO2), monitored over 30 min by using an open-circuit ventilated-canopy system (Deltatrac II monitor, Datex Instrumentarium Corp., Helsinki, Finland) calibrated with a reference gas. Blood samples will be obtained systematically for biological parameters including lipids (cholesterol, HDL-Chol, TG), insulin and glucose values and OGTT (enabling the determination of insulin sensitivity parameters, adipokines and inflammatory parameters such as leptin, adiponectin, IL-6, TNF alpha, SAA, hsCRP. Serum will be kept for all supplementary measures. The histopathological evaluation of subcutaneous adipose tissue will be performed to evaluate the adipocyte size and the degree of tissue inflammation. Stools samples will be collected for metagenomic studies. In addition, blood, urine and fecal water samples will be collected and frozen for subsequent metabonomic analysis, and fecal samples for metaproteomic assessment of the microbiota.

France