Microbial Indoles at the Gut-Immune-Brain Interface During Stress: Metabolism, Signaling, and Neuroimmune Effects
DOI:
https://doi.org/10.15330/jpnubio.13.62-81Keywords:
gut microbiota, tryptophan metabolism, microbial indoles, stress, gut microbiota; tryptophan metabolism; microbial indoles; stress; gut-immune-brain axis; neuroimmunity., neuroimmunityAbstract
Microbial breakdown of dietary tryptophan is a key biochemical bridge connecting gut ecology, mucosal immunity, barrier integrity, and central nervous system function during stress. This narrative review synthesizes current evidence on microbial indole metabolites along the gut-immune-brain axis, separating direct experimental causality from taxonomic associations and non-stress disease models. Luminal substrate availability, fermentable dietary fibres, interspecies cross-feeding, and intestinal pH influence indole output. Upon formation, indole derivatives engage distinct host receptor systems – primarily the aryl hydrocarbon receptor, alongside the pregnane X receptor and peroxisome proliferator-activated receptor beta/delta. Biological outcomes shift considerably across specific chemical species, concentrations, target tissues, and underlying inflammatory states, demonstrating that microbial indoles cannot be generalized as uniformly protective postbiotics. Available evidence suggests that specific microbial indoles may influence sympathoadrenal stress responses, whereas direct links to classic hypothalamic-pituitary-adrenal reactivity remain limited. Highlighting critical methodological gaps, the review concludes that microbial indoles function as dynamic, situational signaling molecules during stress rather than intrinsically protective homeostatic mediators.
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