Gut Microbiota-Dependent Modulation of Energy Metabolism

Abstract

The gut microbiota has emerged as an environmental factor that modulates the host's energy balance. It increases the host's ability to harvest energy from the digested food, and produces metabolites and microbial products such as short-chain fatty acids, secondary bile acids, and lipopolysaccharides. These metabolites and microbial products act as signaling molecules that modulate appetite, gut motility, energy uptake and storage, and energy expenditure. Several findings suggest that the gut microbiota can affect the development of obesity. Germ-free mice are leaner than conventionally raised mice and they are protected against diet-induced obesity. Furthermore, obese humans and rodents have an altered gut microbiota composition with less phylogeneic diversity compared to lean controls, and transplantation of the gut microbiota from obese subjects to germ-free mice can transfer the obese phenotype. Taken together, these findings indicate a role for the gut microbiota in obesity and suggest that the gut microbiota could be targeted to improve metabolic diseases like obesity. This review focuses on the role of the gut microbiota in energy balance regulation and its potential role in obesity.

Keywords: Energy balance; Hypothalamus; Leptin; Metabolites; Microbial products; Microbiota; Obesity; Secondary bile acids; Short-chain fatty acids.

Fig. 1

Gut microbiota-dependent modulation of energy metabolism. Obese humans as well as obese mice have an altered gut microbiota when compared to lean controls, and this gut microbiota composition can transfer the obese phenotype when transplanted into a recipient mouse. Studies using GF, antibiotic-treated, and CONV-R wild-type and mutant mice have shown that the gut microbiota can modulate important processes in the regulation of energy balance. The diet strongly affects the gut microbiota composition and determines which metabolites are produced by the gut microbiota. These metabolites include SCFA and secondary bile acids, which, in turn, can bind to their receptors and thereby activate specific signaling pathways in the host. They can also regulate the secretion of hormones such as GLP-1, PYY, and leptin, which exert their effects in the brain via the circulation or by binding to the vagal afferent nerves. The gut microbiota can also modulate the host's metabolism by microbial products including LPS, which causes low-grade inflammation, and ClpB, which can directly affect the POMC neuronal activity in the hypothalamus. The gut microbiota also has profound effects on intestinal barrier function, the immune system, and the immune response. Together, these signals affect food intake, gut motility, nutrient absorption, and energy utilization and expenditure. SCFAs, short-chain fatty acids; GLP-1, glucagon-like peptide-1; 5-HT, 5-hydroxytryptamine; PYY, peptide YY; LPS, lipopolysaccharide; LPR, leptin receptor; POMC, proopiomelanocortin; CART, cocaine- and amphetamine-regulated transcript; AgRP, agouti-related protein; NPY, neuropeptide Y; MC4R, melanocortin 4 receptor.