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PreprintCC BYbioRxiv

Host genetics determines the fate of the Lactobacillaceae population in the small intestine

  1. 1University of Chicago

Abstract

Whereas innate pattern recognition receptors bind evolutionary conserved moieties shared by diverse groups of microbes, control over closely related microorganisms is likely based on different principles and can be sensitive to genetic variation of the host. While the influence of host genetics on intestinal microbiome composition has been growing in appreciation, understanding of polymorphic mechanisms that regulate individual bacterial lineages requires complex approaches. Using gnotobiotic mouse monocolonized with Ligilactobacillus murinus (ASF361), we found that C57BL/6J (B6) mice harbored significantly more intestinal ASF361 (or other Lactobacillaceae genera) than did BALB/cJ (BALB/c) mice. The difference in ASF361 abundance was independent of adaptive immunity and bacteriotoxic factors. In B6 mice, ASF361 occupied ileal crypts, showed greater expression of adhesion-related molecules, and enriched expression of carbohydrate-metabolism pathways, whereas in BALB/c mice, ASF361 remained largely luminal and enriched expressed genes associated with starvation and stress. These findings highlight the importance of host genetic variation in shaping microbial colonization and suggest that such variation should be considered when evaluating probiotic strains and microbiota transplantation.

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BibTeX
@misc{lietuvninkas2026host,
  title = {{Host genetics determines the fate of the Lactobacillaceae population in the small intestine}},
  author = {H. B. Lietuvninkas and M. J. Coyne and K. Bass and M. Maslyar and E. Cullum and J. Villalobos and A. Chervonsky and T. V. Golovkina},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.25.754556},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.25.754556v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Host genetics determines the fate of the Lactobacillaceae population in the small intestine
AU  - H. B. Lietuvninkas
AU  - M. J. Coyne
AU  - K. Bass
AU  - M. Maslyar
AU  - E. Cullum
AU  - J. Villalobos
AU  - A. Chervonsky
AU  - T. V. Golovkina
PY  - 2026
DA  - 2026/09/25
PB  - bioRxiv
DO  - 10.64898/2026.09.25.754556
UR  - https://www.biorxiv.org/content/10.64898/2026.09.25.754556v1
AB  - Whereas innate pattern recognition receptors bind evolutionary conserved moieties shared by diverse groups of microbes, control over closely related microorganisms is likely based on different principles and can be sensitive to genetic variation of the host. While the influence of host genetics on intestinal microbiome composition has been growing in appreciation, understanding of polymorphic mechanisms that regulate individual bacterial lineages requires complex approaches. Using gnotobiotic mouse monocolonized with Ligilactobacillus murinus (ASF361), we found that C57BL/6J (B6) mice harbored significantly more intestinal ASF361 (or other Lactobacillaceae genera) than did BALB/cJ (BALB/c) mice. The difference in ASF361 abundance was independent of adaptive immunity and bacteriotoxic factors. In B6 mice, ASF361 occupied ileal crypts, showed greater expression of adhesion-related molecules, and enriched expression of carbohydrate-metabolism pathways, whereas in BALB/c mice, ASF361 remained largely luminal and enriched expressed genes associated with starvation and stress. These findings highlight the importance of host genetic variation in shaping microbial colonization and suggest that such variation should be considered when evaluating probiotic strains and microbiota transplantation.
ER  -