Microbiome and Host Health Programme, South Australian Health and Medical Research Institute, Adelaide, South Australia 5001, Australia.
Infection and Immunity, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia 5042, Australia.
ISME J. 2024 Jan 8;18(1). doi: 10.1093/ismejo/wrae107.
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 (Fut2WT or Fut2KO), we examined the abundance and persistence of Bifidobacterium strains (infantis, breve, and bifidum). We observed significant differences in baseline gut microbiota characteristics between Fut2WT and Fut2KO littermates, with Fut2WT mice exhibiting enrichment of species able to utilize α(1,2)-fucosylated glycans. Following antibiotic exposure, only Fut2WT animals showed persistent engraftment of Bifidobacterium infantis, a strain able to internalize α(1,2)-fucosylated glycans, whereas B. breve and 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. infantis persistence was reversed, with Fut2KO animals 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. infantis in the recipient gut, which could potentially contribute to the observed variation in response to this commonly used probiotic species.
益生菌作为一种通过调节宿主-微生物相互作用来改善健康的潜在策略引起了广泛关注，特别是在正常微生物群受到干扰的情况下。然而，关于其疗效的证据一直不一致，个体间的反应存在很大差异。我们旨在探讨一种常见的遗传变异是否可以解释常用益生菌持久性方面观察到的人际差异，这种遗传变异会影响黏膜 α(1,2)-岩藻糖基化聚糖的产生，大约 20%的人群中存在这种变异。我们使用一种具有不同 α(1,2)-岩藻糖基化聚糖分泌能力的小鼠模型（Fut2WT 或 Fut2KO），研究了双歧杆菌属（婴儿双歧杆菌、短双歧杆菌和双歧双歧杆菌）的丰度和持久性。我们观察到 Fut2WT 和 Fut2KO 同窝仔鼠之间的基线肠道微生物群特征存在显著差异，Fut2WT 小鼠表现出能够利用 α(1,2)-岩藻糖基化聚糖的物种富集。在暴露于抗生素后，只有 Fut2WT 动物表现出双歧杆菌属婴儿双歧杆菌的持续定植，这是一种能够内化 α(1,2)-岩藻糖基化聚糖的菌株，而不能内化 α(1,2)-岩藻糖基化聚糖的短双歧杆菌和双歧双歧杆菌则没有表现出这种差异。在具有完整共生菌群的小鼠中，分泌状态和婴儿双歧杆菌持久性之间的关系发生了逆转，Fut2KO 动物比 Fut2WT 动物表现出更强的持久性。我们的研究结果表明，常见遗传变异与抗生素暴露之间的相互作用在决定婴儿双歧杆菌在受体肠道中的动态方面起着至关重要的作用，这可能有助于解释对这种常用益生菌物种反应的可变性。
