
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.20.608888
preprint
1
Article
In utero human intestine contains maternally derived bacterial metabolites
Wang Wenjia
Gu Weihong
Schweitzer Ron
Koren Omry
Khatib Soliman
Tseng George http://orcid.org/0000-0002-5447-1014

Konnikova Liza http://orcid.org/0000-0003-4804-5497

21 8 2024
2024.08.20.608888https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.20.608888
nihpp-2024.08.20.608888.pdf
Abstract

Understanding when host-microbiome interactions are first established is crucial for comprehending normal development and identifying disease prevention strategies. Furthermore, bacterially derived metabolites play critical roles in shaping the intestinal immune system. Recent studies have demonstrated that memory T cells infiltrate human intestinal tissue early in the second trimester, suggesting that intestinal immune education begins in utero. Our previous study reported a unique fetal intestinal metabolomic profile with an abundance of several bacterially derived metabolites and aryl hydrocarbon receptor (AHR) ligands implicated in mucosal immune regulation. To follow up on this work, in the current study, we demonstrate that a number of microbial byproducts present in fetal intestines in utero are maternally derived and vertically transmitted to the fetus. Notably, these bacterially derived metabolites, particularly short chain fatty acids and secondary bile acids, are likely biologically active and functional in regulating the fetal immune system and preparing the gastrointestinal tract for postnatal microbial encounters, as the transcripts for their various receptors and carrier proteins are present in second trimester intestinal tissue through single-cell transcriptomic data.
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pmc
