D-serine metabolism enhances Escherichia coli fitness in the gut and could contribute to Enterobacteriaceae expansion in Crohn's disease patients

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Gut dysbiosis associated with several intestinal and extra-intestinal diseases is frequently characterized by an expansion of Enterobacteriaceae , which typically represent only a few percent of the total gut microbiota in healthy individuals. This expansion can be partially explained by the selection of strains that are metabolically adapted to the altered gut environment. In this study, we performed a phenotypic screening to identify substrates that are differentially catabolized by commensal Escherichia coli strains isolated from healthy individuals (HI) or from patients with Crohn’s disease (CD) or rheumatoid arthritis (RA), two inflammatory diseases associated with gut dysbiosis. While RA strains were metabolically similar to HI strains, CD strains displayed a metabolic pattern with greater dissimilarities. Among the substrates identified, we notably observed opposite metabolic capacities of HI and CD strains to utilize D‑serine and sucrose, a phenotype arising from genetic rearrangements within the argW locus of the E. coli chromosome. The D‑serine–positive phenotype of CD strains was shown to depend on the presence of the dsdCXA genes and to confer a nutritional advantage both in vitro and in vivo . Overall, our findings provide new insights into the metabolic traits that could drive the expansion of Enterobacteriaceae under dysbiotic conditions and highlight D‑serine utilization as a key determinant of E. coli fitness in the gut.

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