Gut microbiota as a regulator of energy homeostasis and ectopic fat deposition: mechanisms and implications for metabolic disorders

Abstract

To examine the role of gut microbiota in the regulation of host energy homeostasis and its role in the pathogenesis of obesity, diabetes and nonalcoholic fatty liver disease (NAFLD). Experimental models highlight several mechanisms connecting gut microbiota to host energy metabolism: increased energy harvesting from the diet, regulation of appetite through gut peptide, secretion, regulation of tissue-free fatty acid composition and uptake, storage and oxidation, modulation of intestinal barrier by glucagon-like peptide-2 secretion, activation of innate immunity and hepatic fibrogenesis through the lipopolysaccharide (LPS)-toll-like receptor-4 axis.Gut microbiota manipulation through antibiotics, prebiotics and probiotics yields encouraging results for the treatment of obesity, diabetes and NAFLD in animal models, but data in humans are currently scarce. Gut microbiota manipulation yielded encouraging results for the treatment of different metabolic disorders in experimental models. However, changing intestinal microbiota may be more difficult in free-living individuals compared to standardized laboratory models, and its long-term consequences are unknown. To safely and effectively change human gut microflora, future research should highlight the complex hormonal, immunomodulatory and metabolic mechanisms underlying microbiota-host interactions in different tissues and candidate treatments should be evaluated in well designed trials with patient-oriented end-points.