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Bifidobacteria infantis and human milk oligosaccharides have independent effects on immune response and amino acid metabolism in germ-free mouse models

ABSTRACT: Early-life microbial colonization is essential for gut and immune development. Human milk oligosaccharides (HMO) support the growth of Bifidobacterium infantis (BI), a keystone infant species. Herein, we studied the individual and combined effects of BI and HMO on immune and colon transcriptomes, and the serum metabolome. Germ-free mice were randomly assigned to four groups [10-14/group: HMO, BI, BI+HMO and control (no HMO or BI)]. HMO and BI+HMO groups received 5 mg/d each of 2′-fucosyllactose, lacto-N-tetraose and 3′-sialyllactose for 14 d. BI and BI+HMO received B. infantis ATCC 15697 (1x10^9 CFU/d) on days 1, 4, and 9. Mono-colonization with BI increased monocytes, macrophages, B cells, CD4+ T cells, and Treg cells in mesenteric lymph nodes (MLN) relative to control. In the spleen, BI alone increased B cells, dendritic cells, Th17 cells, and ILC3 cells, and enriched serum amino acid metabolism pathways. Additionally, BI influenced colonocyte gene expression, and modulated serum metabolites regulating circadian rhythms. BI+HMO increased MLN Th17 cells and spleen monocytes compared to HMO alone. Collectively, the results of this study highlight the complex interplay between host-microbe-diet interactions and emphasize the importance of considering these interactions when designing strategies to modulate infant health during early life.

ORGANISM(S): Mus musculus

PROVIDER: GSE310711 | GEO | 2026/06/01

REPOSITORIES: GEO

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