Colonic nutritional and physicochemical parameters drive gut microbiota dysbiosis in obesity: what we learned from...

Obesity has reached epidemic proportions worldwide with a substantial burden on both individual health and society. Alterations in gut microbiota are increasingly recognized as a key contributor in disease pathogenesis. However, mechanistic understanding at the ecosystem level remains limited. In line with EU and US regulations, in vitro gut systems can be useful to address these questions, but up to now, there is no validated in vitro model of the obese human colon.

To address this gap, we performed dietary surveys and conducted an extensive analysis of 250 articles to set-up and validate a unique in vitro colonic model, based on human in vivo data and reproducing obese-specific nutritional, physicochemical, and lumen vs mucus-associated microbial parameters. Then, in an original experimental set-up, we cross-compared data on gut microbiota structure and activities during fermentations performed with fecal microbiota from healthy (n = 4) or obese (n = 5) donors and operated under healthy or newly designed obese parameters. Interestingly, applying obese parameters on healthy fecal samples resulted in a significant reduction in microbial α-diversity and in taxa associated with health (e.g., Akkermanciaceae, Rikenellaceae, and Archaea), together with a tendency toward increased production of short-chain fatty acids and associated energy, in full agreement with in vivo data. Conversely, applying healthy parameters on obese fecal samples led to gut microbiota resilience.

These findings highlight the importance of nutritional and physicochemical environment in shaping colonic bacterial and archaeal populations in obesity. This innovative validated model represents a robust and useful platform for mechanistic investigations on gut microbiome in the absence of the host cells, as well as for preclinical evaluation of food and pharmaceutical strategies aiming to restore microbiota eubiosis in a personalized manner.