Gut microbiome-intestinal immune axis

The gut microbiome-intestinal immune axis is a complex, bidirectional communication network between the trillions of microorganisms inhabiting the gastrointestinal tract and the host's immune system. This system is fundamental to maintaining immune homeostasis, as commensal bacteria provide essential signals for the development and maturation of gut-associated lymphoid tissues (GALT) and the differentiation of immune cell subsets such as regulatory T cells (Tregs) and Th17 cells (Belkaid & Hand, 2014; Science, 2012). Microbial metabolites, particularly short-chain fatty acids (SCFAs) like butyrate, serve as key signaling molecules that interact with host receptors (e.g., GPR41, GPR43) to modulate inflammation and strengthen the intestinal barrier (BMJ, 2021; GlobalRPH, 2025). Dysregulation of this network, often termed dysbiosis, is linked to a wide range of pathologies, including inflammatory bowel disease (IBD), metabolic syndrome, and neurodegenerative disorders (NIH, 2023; LabRoots, 2022). Therapeutic strategies targeting this axis aim to restore a healthy microbial and immune profile through interventions such as fecal microbiota transplantation (FMT), probiotics, and live biotherapeutics like the FDA-approved Vowst and Rebyota (FDA, 2023; PharmaVoice, 2024). While promising, targeting this network presents significant challenges due to the high inter-individual variability of the microbiome and the potential for unpredictable systemic effects (NIH, 2023).

Other names

Gut-immune axisMicrobiota-immune system crosstalkIntestinal immune networkEnteric signaling networkGut microbiota-host immune system interaction

Modulation of microbial diversity and composition to restore ecological balance; production of short-chain fatty acids (SCFAs) that activate host G protein-coupled receptors (GPR41, GPR43) and inhibit histone deacetylases (HDACs); activation of the aryl hydrocarbon receptor (AhR) to enhance barrier function; and induction of regulatory T cells (Tregs) to suppress pathological inflammation (BMJ, 2021; GlobalRPH, 2025; NIH, 2023).