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.