The Gut Microbiome as a Metabolic Signalling Organ in Obesity: From Energy Harvest to Immune Regulation

Obesity affects over 890 million adults and remains a major driver of non-communicable disease burden. The gut microbiome is increasingly recognised to influence energy harvest, immune regulation and host metabolism through altered microbial metabolites. Obesity-related gut dysbiosis signatures include reduced microbial diversity, depletion of beneficial taxa including the barrier-supporting Akkermansia muciniphila and the short-chain fatty acid (SCFA)-producing Faecalibacterium prausnitzii, inconsistent findings for the Firmicutes/Bacteroidetes ratio and species-level shifts reported in several cohorts including depletion of Alistipes finegoldii. Proposed mechanisms include enhanced energy harvest, SCFA-mediated regulation of adiposity and inflammation, bile acid signalling, gut-brain appetite signalling, intestinal barrier dysfunction and immune dysregulation. Early-life microbial perturbations may further shape long-term obesity risk through developmental programming. Maternal obesity, caesarean delivery, formula feeding and antibiotic exposure may seed obesogenic profiles, whereas breastfeeding is associated with enrichment of Bifidobacterium and SCFA-producing bacteria. Interventions such as dietary modulation, prebiotics, next-generation probiotics and bariatric surgery show therapeutic potential, although causality remains unproven in most human studies.Future research should prioritise phenotype-stratified randomised controlled trials, Mendelian randomisation studies and longitudinal cohorts to establish mechanistic links between gut microbiota and obesity. Overall, this review reframes obesity as a disorder of disrupted metabolic and immune signalling and positions the gut microbiome as a promising target for precision strategies aimed at restoring metabolic and immune homeostasis.