4.7 Article

Microbial bile salt hydrolase activity influences gene expression profiles and gastrointestinal maturation in infant mice

Journal

GUT MICROBES
Volume 14, Issue 1, Pages -

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/19490976.2022.2149023

Keywords

Bile; organoid; colon; neonatal; infant; gut development; intestine; stem cell

Funding

  1. European Union [16/IA/4445]
  2. Science Foundation Ireland [796838, SFI/12/RC/2273]
  3. Science Foundation Ireland (SFI) [16/IA/4445] Funding Source: Science Foundation Ireland (SFI)

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Research has found that the activity of microbial bile salt hydrolase (BSH) potentially influences bacterial colonization and promotes infant gut development. This study is of great significance for understanding the mechanisms by which early microbial colonizers affect gut development.
The mechanisms by which early microbial colonizers of the neonate influence gut development are poorly understood. Bacterial bile salt hydrolase (BSH) acts as a putative colonization factor that influences bile acid signatures and microbe-host signaling pathways and we considered whether this activity can influence infant gut development. In silico analysis of the human neonatal gut metagenome confirmed that BSH enzyme sequences are present as early as one day postpartum. Gastrointestinal delivery of cloned BSH to immature gnotobiotic mice accelerated shortening of the colon and regularized gene expression profiles, with monocolonised mice more closely resembling conventionally raised animals. In situ expression of BSH decreased markers of cell proliferation (Ki67, Hes2 and Ascl2) and strongly increased expression of ALPI, a marker of cell differentiation and barrier function. These data suggest an evolutionary paradigm whereby microbial BSH activity potentially influences bacterial colonization and in-turn benefits host gastrointestinal maturation.

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