Intestinal persistence of Bifidobacterium infantisis determined by interaction of host genetics and antibiotic exposure

Probiotics have gained significant attention as a potential strategy to improve health by modulating host–microbe interactions, particularly in situations where the normal microbiota has been disrupted. However, evidence regarding their efficacy has been inconsistent, with considerable interindividual variability in response. We aimed to explore whether a common genetic variant that affects the production of mucosal α(1,2)-fucosylated glycans, present in around 20% of the population, could explain the observed interpersonal differences in the persistence of commonly used probiotics. Using a mouse model with varying α(1,2)-fucosylated glycans secretion (Fut2WTor Fut2KO), we examined the abundance and persistence of Bifidobacteriumstrains (infantis, breve,and bifidum). We observed significant differences in baseline gut microbiota characteristics between Fut2WTand Fut2KOlittermates, with Fut2WTmice exhibiting enrichment of species able to utilize α(1,2)-fucosylated glycans.Following antibiotic exposure, only Fut2WTanimals showed persistent engraftment of Bifidobacterium infantis, a strain able to internalize α(1,2)-fucosylated glycans, whereas B. breveand B. bifidum, which cannot internalize α(1,2)-fucosylated glycans, did not exhibit this difference. In mice with an intact commensal microbiota, the relationship between secretor status and B. infantispersistence was reversed, with Fut2KOanimals showing greater persistence compared to Fut2WT. Our findings suggest that the interplay between a common genetic variation and antibiotic exposure plays a crucial role in determining the dynamics of B. infantisin the recipient gut, which could potentially contribute to the observed variation in response to this commonly used probiotic species.