Unraveling the gut microbiota's role in obesity: key metabolites, microbial species, and therapeutic insights.

Abstract

Obesity, characterized by excessive fat accumulation, stems from an imbalance between energy intake and expenditure, with the gut microbiota playing a crucial role. This review highlights how gut microbiota influences metabolic pathways, inflammation, and adipose tissue regulation in obesity. Specific bacteria and metabolites, such as lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs), modulate gut permeability, inflammation, and energy harvest, impacting obesity development. Certain gut bacteria, including Clostridium XIVb, Dorea spp., Enterobacter cloacae, and Collinsella aerofaciens, promote obesity by increasing energy harvest, gut permeability, and inflammatory response through LPS translocation into the bloodstream. Conversely, beneficial bacteria like Akkermansia muciniphila, Lactobacillus spp., and Bifidobacterium spp. enhance gut barrier integrity, regulate SCFA production, and modulate fasting-induced adipose factor, which collectively support metabolic health by reducing fat storage and inflammation. Metabolites such as SCFAs (acetate, propionate, and butyrate) interact with G-protein coupled receptors to regulate lipid metabolism and promote the browning of white adipose tissue (WAT), thus enhancing thermogenesis and energy expenditure. However, LPS contributes to insulin resistance and fat accumulation, highlighting the dual roles of these microbial metabolites in both supporting and disrupting metabolic function. Therapeutic interventions targeting gut microbiota, such as promoting WAT browning and activating brown adipose tissue (BAT), hold promise for obesity management. However, personalized approaches are necessary due to individual microbiome variability. Further research is essential to translate these insights into microbiota-based clinical therapies.