Gut-relevant short-chain fatty acids modulate host-pathogen dynamics of uropathogenic Escherichia coli at the colonic epithelial interface

Yuen, N.; Maset, R. G.; Wang, W.; Kubal, M.; Chen, Z.; Chu, V.; White, I. J.; Gao, J.; Torelli, F.; Crowther, A.; Pasquina-Lemonche, L.; Rohn, J.

doi:10.64898/2026.01.19.700340

bioRxiv · 10.64898/2026.01.19.700340

Gut-relevant short-chain fatty acids modulate host-pathogen dynamics of uropathogenic Escherichia coli at the colonic epithelial interface

Yuen, N.·Maset, R. G.·Wang, W.·Kubal, M.·Chen, Z.·Chu, V.·White, I. J.·Gao, J.·Torelli, F.·Crowther, A.·Pasquina-Lemonche, L.·Rohn, J.

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Abstract

Urinary tract infection (UTI) ranks among the most prevalent bacterial infections worldwide, affecting over 400 million people each year. Uropathogenic Escherichia coli (UPEC), the main aetiological cause of UTI, colonises the intestinal tract, which is thought to serve as a distal reservoir for gut-UTI recurrence. Despite this, the precise role of the gut in UTI recurrence is still not fully defined. Recent research investigating the gut-UTI axis has revealed that reduced abundance of gut commensals producing short-chain fatty acids (SCFAs, namely acetate, butyrate and propionate) is associated with recurrent and chronic UTI. We therefore aimed to investigate the impact of these gut commensal-derived metabolites on a diverse panel of UPEC strains, including well-studied prototypical strains (UTI89, CFT073), a non-pathogenic isolate E. coli K-12, and various clinical UTI isolates (from the urine of both symptomatic and asymptomatic individuals). We observed that SCFAs modulate bacterial growth kinetics in a concentration- and pH-dependent manner, by prolonging the lag phase without affecting final carrying capacity in vitro. These metabolites further suppressed bacterial swimming motility and biased the orientation of fimS, the phase variable switch for T1 fimbriae, under acidic conditions. In a human polarized, mucus-secreting intestinal infection model, SCFA treatment during UPEC challenge altered bacterial localization patterns, favouring planktonic over mucosal-associated populations, and preserved epithelial barrier function. Together, these in vitro findings demonstrate that SCFAs modulate key UPEC colonization-associated phenotypes and influence host-pathogen dynamics at the colonic epithelial interface. These results provide mechanistic insights into how depletion of SCFA-producing gut commensals may alter the intestinal reservoir environment in vitro and warrants further investigation into the role of gut-derived SCFAs in rUTI susceptibility.

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Yuen, N., Maset, R. G., Wang, W., Kubal, M., Chen, Z., Chu, V., White, I. J., Gao, J., Torelli, F., Crowther, A., Pasquina-Lemonche, L., Rohn, J.. 2026-01-19. Gut-relevant short-chain fatty acids modulate host-pathogen dynamics of uropathogenic Escherichia coli at the colonic epithelial interface. https://doi.org/10.64898/2026.01.19.700340

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