Gut Microbial Bile Acid Signaling as a Shared Therapeutic Axis in Obesity and Diabetes
Winniefred Nankya
Department of Clinical Pharmacy Kampala International University Uganda
Email:winniefred.nankya@studwc.kiu.ac.ug
ABSTRACT
Bile acids (BAs) have emerged as pleiotropic signaling molecules that connect gut microbiota, liver, intestine, and peripheral metabolic tissues. Beyond their classical role in lipid absorption, BAs act as endocrine regulators via receptors such as the farnesoid X receptor (FXR) and the G-protein–coupled receptor TGR5, shaping glucose and lipid metabolism, energy expenditure, and inflammation. Gut microbes profoundly remodel the BA pool through bile salt hydrolase (BSH) and other enzymes, altering receptor affinity and signaling bias. Dysbiosis in obesity (OB) and type 2 diabetes (T2D) perturbs this “microbiota–BA axis,”, contributing to insulin resistance, fatty liver, and impaired incretin responses. This review frames gut microbial BA signaling as a shared therapeutic axis in OB and T2D. We summarize BA synthesis and microbial transformations, then detail how BA receptors integrate microbial cues to control hepatic gluconeogenesis, adipose and muscle insulin sensitivity, incretin (GLP-1) secretion, and energy expenditure. We highlight human and preclinical data linking altered BA profiles and receptor activity to metabolic disease, including mechanistic insights from bariatric surgery, BA sequestrants, and FXR/TGR5-targeted drugs. We further discuss next-generation strategies that exploit microbiota-derived BA species or receptor-selective agonists, including microbial amino acid–conjugated BAs that stimulate GLP-1 via novel G-protein–coupled receptors. Finally, we outline biomarker and precision-medicine opportunities based on BA and microbiome signatures, and key knowledge gaps for safely manipulating this axis in chronic metabolic disease. Understanding and harnessing gut microbial BA signaling may allow convergent treatments that simultaneously tackle OB, T2D, and associated liver disease.
Keywords: bile acids; gut microbiota; FXR; TGR5; GLP-1
CITE AS: Winniefred Nankya (2026). Gut Microbial Bile Acid Signaling as a Shared Therapeutic Axis in Obesity and Diabetes. IAA Journal of Biological Sciences 14(1):75-81.