The gut microbiome and colonic pH shape the peripheral immune landscape in humans
Dinakis, E.; Rhys-Jones, D.; Camargo Tavares, L.; Yang, C.; Yao, C.; So, D.; Anderson, D.; Creek, D.; Turner, S. J.; Gibson, P. R.; Mackay, C. R.; O'Donnell, J. A.; Muir, J.; Marques, F.
Show abstract
The physicochemical environment of the gut, particularly colonic pH, plays a critical role in shaping host-microbe interactions; yet its influence on systemic immunity in humans remains poorly understood. Here, we integrated faecal metagenomics, plasma short-chain fatty acid (SCFA) profiling, SmartPill wireless pH-motility capsule data, and deep immunophenotyping of peripheral blood mononuclear cells in a cross-sectional study of 54 healthy participants to investigate the relationship between colonic pH, microbial metabolism, and immune tone. We found that lower colonic pH was associated with cytokine-producing CD8+ T cells, while higher pH correlated with pre-exhausted CD8+ T cells and elevated neutrophil populations. Metagenomic analyses revealed species-level associations within the genus Eubacterium, linked to colonic pH and peripheral immune profiles. These findings suggest that microbial metabolic activity and gut pH may work together to jointly modulate immune tone beyond the gut in humans, establishing a functional axis between microbial fermentation, physicochemical gut conditions, and systemic immunity.
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