Review Unpacks Gut Microbiome-Endocrine Axis, Detailing Microbial Metabolite Impact on Obesity and Therapeutic Strategies

Obesity, a major global health challenge, represents a state of dysregulated energy homeostasis and a key risk factor for metabolic diseases. While the gut microbiome has emerged as a critical mediator of obesity pathogenesis, the precise endocrine mechanisms linking microbial signals to metabolic dysfunction remain incompletely understood. This review addresses this gap by elucidating the gut microbiome-endocrine axis, encompassing gut-brain, gut-adipose, and gut-pancreas axes. Understanding this intricate interplay is crucial, as current standard-of-care often overlooks the profound influence of microbial signals on systemic endocrine homeostasis.

This comprehensive review systematically elucidated the mechanisms of the gut microbiome-endocrine axis in obesity. It synthesized existing literature on how gut microbiota and their metabolites, including short-chain fatty acids, bile acids, and microbial peptides, influence systemic endocrine homeostasis through energy intake, fat storage, and hormonal secretion. The review further summarized current therapeutic approaches targeting the gut microbiome, such as prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation (FMT), and lifestyle interventions, highlighting their mechanistic and translational relevance.

The review found that gut microbiota and their metabolites significantly modulate systemic endocrine homeostasis across the gut-brain, gut-adipose, and gut-pancreas axes. Specifically, short-chain fatty acids, bile acids, and microbial peptides were identified as key mediators influencing energy intake, fat storage, and hormonal secretion. These microbial signals impact host metabolism through diverse signaling pathways and metabolite production. Therapeutic strategies targeting the gut microbiome, including prebiotics, probiotics, synbiotics, postbiotics, fecal microbiota transplantation (FMT), and lifestyle modifications, demonstrate potential in modulating this axis for obesity control. The review highlighted that these interventions can influence microbial composition and function, thereby impacting host endocrine responses and metabolic health. Challenges remain in precise phenotyping, cross-organ integration, and establishing causal inference, suggesting future research directions involving integrated models and AI-driven causal modeling.

The gut microbiome's influence on endocrine function is multifaceted, impacting host metabolism through diverse signaling pathways and metabolite production, offering novel therapeutic targets for obesity.