Genome-scale resources in the infant gut symbiont Bifidobacterium breve reveal genetic determinants of colonization and host-microbe interactions.

Shiver AL, Sun J, Culver R, Violette A, Wynter C, Nieckarz M, Mattiello SP, Sekhon PK, Bottacini F, Friess L, Carlson HK, Wong DPGH, Higginbottom S, Weglarz M, Wang W, Knapp BD, Guiberson E, Sanchez J, Huang PH, Garcia PA, Buie CR, Good BH, DeFelice B, Cava F, Scaria J, Sonnenburg JL, Van Sinderen D, Deutschbauer AM, Huang KC

Cell 188 (7) 2003-2021.e19 [2025-04-03; online 2025-03-10]

Bifidobacteria represent a dominant constituent of human gut microbiomes during infancy, influencing nutrition, immune development, and resistance to infection. Despite interest in bifidobacteria as a live biotic therapy, our understanding of colonization, host-microbe interactions, and the health-promoting effects of bifidobacteria is limited. To address these major knowledge gaps, we used a large-scale genetic approach to create a mutant fitness compendium in Bifidobacterium breve. First, we generated a high-density randomly barcoded transposon insertion pool and used it to determine fitness requirements during colonization of germ-free mice and chickens with multiple diets and in response to hundreds of in vitro perturbations. Second, to enable mechanistic investigation, we constructed an ordered collection of insertion strains covering 1,462 genes. We leveraged these tools to reveal community- and diet-specific requirements for colonization and to connect the production of immunomodulatory molecules to growth benefits. These resources will catalyze future investigations of this important beneficial microbe.

PubMed 40068681

DOI 10.1016/j.cell.2025.02.010

Crossref 10.1016/j.cell.2025.02.010

mid: NIHMS2180650
pmc: PMC13403077
pii: S0092-8674(25)00195-3