Cited by 27Gut microbiota and healthProbiotics and Fermented FoodsInfant Nutrition and Health

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

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Shiver, Anthony L., Sun, Jiawei, Culver, Rebecca, Violette, Arvie, Wynter, Char, Nieckarz, Marta, Mattiello, Samara Paula, Sekhon, Prabhjot Kaur +21 more·2025·Cell

Abstract

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.

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Crossref · 10.1016/j.cell.2025.02.010

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  • B. bifidum is characteristic of the bifidobacterial communities residing in the infant gut and contributes to early microbial colonization, alongside B. breve.

    “B. bifidum is characteristic of the bifidobacterial communities residing in the infant gut and contributes to early microbial colonization, alongside Bifidobacterium breve [6-10] .”

    From Genome-scale insights into the metabolic landscape and evolutionary development of Bifidobacterium bifidum (2026) · cites this paper as [7]

    The Introduction describes bifidobacteria as early colonizers of the human gut and identifies B. breve as preferentially associated with infants. The Methods list B. bifidum among human-residential species, but the cited passages do not establish that B. bifidum specifically is characteristic of infant gut communities or contributes to early colonization. No page numbers are available in our copy. (LLM, conf=0.86)

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Research works printed but not linked: 4

  1. [37]Meng D, Sommella E, Salviati E, Campiglia P, Ganguli K, Djebali K, Zhu W, and Walker WA (2020). Indole-3-lactic acid, a metabolite of tryptophan, secreted by Bifidobacterium longum subspecies infantis is anti-inflammatory in the immature intestine. Pediatr Res 88, 209– 217. 10.1038/s41390-019-0740-x. 31945773 PMC7363505 · DOI
  2. [41]Wetmore Kelly M., Price Morgan N., Waters Robert J., Lamson Jacob S., He J, Hoover Cindi A., Blow Matthew J., Bristow J, Butland G, Arkin Adam P., and Deutschbauer A (2015). Rapid Quantification of Mutant Fitness in Diverse Bacteria by Sequencing Randomly Bar-Coded Transposons. mBio 6, e00306–00315. 10.1128/mBio.00306-15. PMC4436071 25968644 · DOI
  3. [64]Goodman AL, McNulty NP, Zhao Y, Leip D, Mitra RD, Lozupone CA, Knight R, and Gordon JI (2009). Identifying genetic determinants needed to establish a human gut symbiont in its habitat. Cell Host Microbe 6, 279– 289. 10.1016/j.chom.2009.08.003. 19748469 PMC2895552 · DOI
  4. [146]Wetmore KM, Price MN, Waters RJ, Lamson JS, He J, Hoover CA, Blow MJ, Bristow J, Butland G, Arkin AP, and Deutschbauer A (2015). Rapid quantification of mutant fitness in diverse bacteria by sequencing randomly bar-coded transposons. mBio 6, e00306– 00315. 10.1128/mBio.00306-15. 25968644 PMC4436071 · DOI

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Authors
Shiver, A. L., Sun, J., Culver, R., Violette, A., Wynter, C., Nieckarz, M., Mattiello, S. P., Sekhon, P. K., Bottacini, F., Friess, L., Carlson, H. K., Wong, D. P. G. H., Higginbottom, S., Weglarz, M., Wang, W., Knapp, B. D., Guiberson, E., Sanchez, J., Huang, P.-H., Garcia, P. A., Buie, C. R., Good, B. H., DeFelice, B., Cava, F., Scaria, J., Sonnenburg, J. L., Van Sinderen, D., Deutschbauer, A. M., & Huang, K. C.
Affiliations
  • Stanford University (US)
  • Science for Life Laboratory (SE)
  • South Dakota State University (US)
  • Oklahoma State University (US)
  • University College Cork (IE)
  • Lawrence Berkeley National Laboratory (US)
  • Stanford Medicine (US)
  • Middlebury College (US)
  • Massachusetts Institute of Technology (US)
  • Chan Zuckerberg Biohub San Francisco (US)
Corresponding author
Huang, Kerwyn Casey
Venue
Cell
Publisher
Elsevier BV
Published
2025-04
Volume
188
Issue
7
Pages
2003-2021.e19
ISSN
0092-8674 (ISSN-L)
OpenAlex
W4408290372
Cited by
27
References
141
Citations by year
2026: 16 · 2025: 11
FWCI
8.12
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
Funders
  • NIH National Institute of General Medical Sciences (RM1 GM135102, R35 GM146949)
  • National Science Foundation (EF-2125383, IOS-2032985)
  • Svenska Sällskapet för Medicinsk Forskning
  • Vetenskapsrådet
  • Science Foundation Ireland (SFI/12/RC/2273-P2, SFI/12/RC/2273-P1)
  • Knut och Alice Wallenbergs Stiftelse
  • National Defense Science and Engineering Graduate
  • National Institutes of Health
  • Kempe Foundation
  • National Institute of Allergy and Infectious Diseases Division of Intramural Research (R01 AI147023)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
  • Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
Keywords
Bifidobacterium breve, infant gut microbiota, intestinal colonization, host-microbe interactions, transposon mutant library, germ-free mice, chickens, diet, immunomodulatory molecules, probiotics
MeSH terms
Gastrointestinal Microbiome, Bifidobacterium breve, Host Microbial Interactions, Animals, Chickens, DNA Transposable Elements, Female, Germ-Free Life, Humans, Infant, Mice, Inbred C57BL, Symbiosis, Genome, Bacterial, Mice

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