Link between gut microbiota and health outcomes in inulin -treated obese patients: Lessons from the Food4Gut multicenter randomized placebo-controlled trial
Sophie Hiel, Marco A. Gianfrancesco, Julie Rodriguez, Daphnée Portheault, Quentin Leyrolle, Laure B. Bindels, Carolina Gomes da Silveira Cauduro, Maria D.G.H. Mulders, Giorgia Zamariola, Anne‐Sophie Azzi, Gaétan Kalala, Barbara D. Pachikian, Camille Amadieu, Audrey M. Neyrinck, Audrey Loumaye, Patrice D. Cani, Nicolas Lanthier, Pierre Tréfois, Olivier Klein, Olivier Luminet, Jérôme Bindelle, Nicolas Paquot, Miriam Cnop, Jean‐Paul Thissen, Nathalie M. Delzenne
Abstract
BACKGROUND: The gut microbiota is altered in obesity and is strongly influenced by nutrients and xenobiotics. We have tested the impact of native inulin as prebiotic present in vegetables and added as a supplement on gut microbiota-related outcomes in obese patients. Metformin treatment was analyzed as a potential modulator of the response. METHODS: A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in 150 obese patients who received 16 g/d native inulin versus maltodextrin, coupled to dietary advice to consume inulin-rich versus -poor vegetables for 3 months, respectively, in addition to dietary caloric restriction. Anthropometry, diagnostic imaging (abdominal CT-scan, fibroscan), food-behavior questionnaires, serum biology and fecal microbiome (primary outcome; 16S rDNA sequencing) were analyzed before and after the intervention. RESULTS: Both placebo and prebiotic interventions lowered energy intake, BMI, systolic blood pressure, and serum γ-GT. The prebiotic induced greater weight loss and additionally decreased diastolic blood pressure, AST and insulinemia. Metformin treatment compromised most of the gut microbiota changes and metabolic improvements linked to prebiotic intervention. The prebiotic modulated specific bacteria, associated with the improvement of anthropometry (i.e. a decrease in Desulfovibrio and Clostridium sensu stricto). A large increase in Bifidobacterium appears as a signature of inulin intake rather than a driver of prebiotic-linked biological outcomes. CONCLUSIONS: Inulin-enriched diet is able to promote weight loss in obese patients, the treatment efficiency being related to gut microbiota characteristics. This treatment is more efficacious in patients who did not receive metformin as anti-diabetic drugs prior the intervention, supporting that both drug treatment and microbiota might be taken into account in personalized nutrition interventions. Registered under ClinicalTrials.gov Identifier no NCT03852069.