Microbial dysbiosis-induced obesity: role of gut microbiota in homoeostasis of energy metabolism

The global obesity epidemic has necessitated the search for better intervention strategies including the exploitation of the health benefits of some gut microbiota and their metabolic products. Therefore, we examined the gut microbial composition and mechanisms of interaction with the host in relation to homoeostatic energy metabolism and pathophysiology of dysbiosis-induced metabolic inflammation and obesity. We also discussed the eubiotic, health-promoting effects of probiotics and prebiotics as well as epigenetic modifications associated with gut microbial dysbiosis and risk of obesity. High-fat/carbohydrate diet programmes the gut microbiota to one predominated by Firmicutes (Clostridium), Prevotella and Methanobrevibacter but deficient in beneficial genera/species such as Bacteroides, Bifidobacterium, Lactobacillus and Akkermansia. Altered gut microbiota is associated with decreased expression of SCFA that maintain intestinal epithelial barrier integrity, reduce bacterial translocation and inflammation and increase expression of hunger-suppressing hormones. Reduced amounts of beneficial micro-organisms also inhibit fasting-induced adipocyte factor expression leading to dyslipidaemia. A low-grade chronic inflammation (metabolic endotoxaemia) ensues which culminates in obesity and its co-morbidities. The synergy of high-fat diet and dysbiotic gut microbiota initiates a recipe that epigenetically programmes the host for increased adiposity and poor glycaemic control. Interestingly, these obesogenic mechanistic pathways that are transmittable from one generation to another can be modulated through the administration of probiotics, prebiotics and synbiotics. Though the influence of gut microbiota on the risk of obesity and several intervention strategies have been extensively demonstrated in animal models, application in humans still requires further robust investigation.