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

Abstract

Abstract Background 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 inter-individual 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. Methods A mouse model in which littermates varied in their ability to secrete α(1, 2)-fucosylated glycans (Fut2WT or Fut2KO) was utilised to explore the abundance and persistence of three common strains of probiotic Bifidobacterium species (infantis, breve and bifidum). Fut2WT and Fut2KO mice were gavaged daily for 5 days with either B. infantis, B. breve or B. bifidum, following either antibiotic pre-exposure or no antibiotic exposure. Stool and intestinal tissue were collected at defined periods throughout, and microbiota composition and bifidobacterial levels assessed. In vitro growth assays were performed on stool using media either supplemented with or without 2'-fucosyllactose. Results We observed significant differences in baseline gut microbiota characteristics between Fut2WT and Fut2KO littermates, with Fut2WT mice exhibiting enrichment of species able to utilise α(1, 2)-fucosylated glycans. Following antibiotic exposure, only Fut2WT animals showed persistent engraftment of Bifidobacterium infantis, a strain able to internalise α(1, 2)-fucosylated glycans, while B. breve and B. bifidum, which cannot internalise α(1, 2)-fucosylated glycans, did not exhibit this difference. In mice with an intact commensal microbiota, the relationship between secretor status and B. infantis persistence was reversed, with Fut2KO animals showing greater persistence compared to Fut2WT. Conclusions Our findings suggest that the interplay between a common genetic variation and antibiotic exposure plays a crucial role in determining the dynamics of B. infantis in the recipient gut, which could potentially contribute to the observed variation in response to this commonly used probiotic species.