Intestinal-related substances in obesity regulation: A comprehensive review

With the rising global obesity rates, particularly in industrialized nations, obesity has become an increasingly significant public health concern. This review analyzes 132 relevant studies published between 2020 and 2025, with a focus on the role of gut-derived substances in regulating obesity. These include gut hormones such as glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide YY, cholecystokinin, and ghrelin, microbial metabolites such as short-chain fatty acids (SCFA) and indole-3-propionic acid (IPA), and neurotransmitters (such as serotonin and dopamine).The findings suggest that gut hormones play a crucial role in regulating appetite, glucose metabolism, and energy expenditure, and their dysregulation is closely linked to the development of obesity. Moreover, microbial metabolites like SCFA and IPA are strongly associated with metabolic health and significantly influence obesity-related mechanisms. This review also explores emerging therapeutic strategies, including GLP-1 receptor agonists, dual GLP-1/GIP receptor agonists, modulation of the gut microbiota, and fecal microbiota transplantation, all of which demonstrate promising potential in obesity management. However, challenges remain in optimizing these interventions, mitigating adverse effects, and establishing regulatory standards for microbiota-based therapies. Future research should aim to develop personalized, multi-targeted approaches to more effectively combat obesity and its associated metabolic disorders.