Immune system via indirect microbiota-mediated pathways (None)

The gut microbiota-immune axis refers to the complex bidirectional communication between commensal microorganisms and the host's immune system. This interaction is primarily mediated by microbial metabolites, such as short-chain fatty acids (SCFAs), bile acids, and tryptophan derivatives, which act as signaling molecules (Belkaid & Hand, 2014, Science). These metabolites bind to specific host receptors, including G-protein coupled receptors (GPCRs) and the aryl hydrocarbon receptor (AhR), to influence immune cell differentiation and function (Rooks & Garrett, 2016, Nature Reviews Immunology). This pathway is critical for the induction of regulatory T cells (Tregs) and the maintenance of intestinal barrier integrity, which prevents systemic inflammation (Koh et al., 2016, Cell). Dysregulation of this axis, known as dysbiosis, is associated with various conditions such as inflammatory bowel disease, allergies, and metabolic syndrome. Furthermore, the composition of the gut microbiota has been shown to significantly impact the efficacy of cancer immunotherapies, particularly checkpoint inhibitors (Gopalakrishnan et al., 2018, Science). Therapeutic interventions like fecal microbiota transplantation (FMT) and the administration of probiotics or prebiotics aim to modulate this system to restore homeostasis. Unlike traditional molecular targets, this "target" represents a multi-component biological system involving diverse microbial species and their metabolic outputs. Consequently, drug development in this space focuses on ecological shifts and metabolic signaling rather than single-protein inhibition or activation.

Other names

Gut microbiota-immune axisMicrobiome-immune axisMicrobiota-host immune crosstalkGut-immune axis

Modulation of the commensal microbial community to alter the production of immunomodulatory metabolites that signal through host receptors to regulate immune cell activity and maintain mucosal homeostasis.