Year: 2026
Type: review
Abstract: Host-microbe interactions within the gut have been extensively reviewed in the context of host immune response. Emerging evidence, however, highlights that these inflammatory and immune outcomes are often deeply intertwined with the microbiome-derived secondary metabolites. The gut microbiota functions in concert with the host by providing an extensive repertoire of metabolic enzymes that enhance digestion and capacity to assimilate a broad spectrum of ingested food sources. This symbiotic metabolism generates a diverse array of bioactive metabolites that shape local and systemic physiology, adaptive immune responses, and neuroimmune responses. Here, we focus on microbial metabolism as a central organizing principle of host-microbiota symbiosis. Microbiota-derived metabolites, including short-chain fatty acids, secondary bile acids, tryptophan-derived indoles, sphingolipids, and gaseous byproducts, signal through downstream molecular partners like nuclear receptors, transcriptional regulators, and redox-sensitive homeostatic pathways to regulate host energy homeostasis, but also alter immune functions like gut epithelial integrity, immune tolerance, and neuroimmune crosstalk. Finally, we discuss emerging therapeutic strategies that target microbial metabolic functions-including dietary interventions, engineered probiotics, postbiotics, and receptor-directed approaches-that position microbial metabolism as a tractable axis for modulating immunometabolism homeostasis and potentially mitigating metabolic and inflammatory diseases.
Source: FEBS Journal
DOI: 10.1111/febs.70704
Institution: University of Southern California
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
Funder: National Institute on Aging
OpenAlex ID: W7204882446