Current Pharmaceutical Design, 2009, 15, 1546-1558

The Role of the Gut Microbiota in Energy Metabolism and Metabolic Disease

Patrice D. Cani* and Nathalie M. Delzenne*
Université catholique de Louvain, Louvain Drug Research Institute, Unit of Pharmacokinetics, Metabolism,
Nutrition and Toxicology, Brussels, Belgium

Abstract: Obesity is now classically characterized by a cluster of several metabolic disorders, and by a low grade inflammation.
The evidence that the gut microbiota composition can be different between healthy and or obese and type 2 diabetic patients
has led to the study of this environmental factor as a key link between the pathophysiology of metabolic diseases and the gut microbiota.
Several mechanisms are proposed linking events occurring in the colon and the regulation of energy metabolism, such as i.e.
the energy harvest from the diet, the synthesis of gut peptides involved in energy homeostasis (GLP-1, PYY…), and the regulation
of fat storage. Moreover, the development of obesity and metabolic disorders following a high-fat diet may be associated to the innate
immune system. Indeed, high-fat diet feeding triggers the development of obesity, inflammation, insulin resistance, type 2 diabetes and
atherosclerosis by mechanisms dependent of the LPS and/or the fatty acids activation of the CD14/TLR4 receptor complex.
Importantly, fat feeding is also associated with the development of metabolic endotoxemia in human subjects and participates in
the low-grade inflammation, a mechanism associated with the development of atherogenic markers. Finally, data obtained in experimental
models and human subjects are in favour of the fact that changing the gut microbiota (with prebiotics and/or probiotics) may participate
in the control of the development of metabolic diseases associated with obesity. Thus, it would be useful to find specific strategies
for modifying gut microbiota to impact on the occurrence of metabolic diseases.