The effects of microbiota-derived short-chain fatty acids on T lymphocytes: From autoimmune diseases to cancer.
Level 5 - mechanism / opinion, no new human data
Narrative review of mechanistic and preclinical literature without systematic search methodology
PubMed 40834607 · doi:10.1016/j.seminoncol.2025.152398
What was done
The authors synthesized literature on how microbiota-derived short-chain fatty acids (SCFAs; acetate, propionate, butyrate) regulate T lymphocyte biology, reviewing underlying mechanisms (histone deacetylase inhibition, G-protein-coupled receptor signaling, and metabolic reprogramming) and their roles in autoimmune diseases and cancer.
What was found
The abstract reports no quantitative primary data or pooled effect sizes. It qualitatively reports that butyrate enhances regulatory T cell (Treg) and IL-10-producing Th1 differentiation while regulating Th17 development in a context-dependent manner. SCFAs enhance CD8+ cytotoxic T-cell memory formation, IFN-γ production, and antitumor/antiviral immunity, potentially amplifying the efficacy of checkpoint inhibitors like anti-PD-1 via ID2 regulation. SCFAs reprogram metabolism through acetyl-CoA generation, mTOR signaling, and fatty acid oxidation, and induce apoptosis in activated T cells by upregulating Fas via HDAC1 inhibition.
Why it matters
This review maps the mechanistic links between gut microbial metabolites and T-cell signaling pathways. It outlines potential therapeutic targets for modulating immune tolerance in autoimmune disorders or boosting antitumor immunity during immunotherapy.
Limits
This is a narrative review presenting no new clinical data or systematic synthesis. The abstract does not specify literature search criteria, sample sizes, or distinguish between findings from in vitro cell models, animal studies, and human clinical trials.
Cited by
- supports Short-chain fatty acids produced by gut bacteria fermentation, including acetate, butyrate, and propionate, increase the number of regulatory T cells to modulate autoimmune responses.