In utero human intestine contains maternally derived bacterial metabolites

Area of Science:

• Maternal-fetal medicine
• Microbiome research
• Immunology

Background:

• Host-microbiome interactions are critical for development and disease prevention.
• Bacterially derived metabolites shape the fetal intestinal immune system.
• Memory T cells and microbial metabolites are present in utero.

Purpose of the Study:

• To investigate the presence and origin of microbiome-associated metabolites in the fetal environment.
• To determine the potential role of these metabolites in fetal immune development.

Main Methods:

• Metabolomic profiling of fetal intestinal, meconium, placental, and maternal decidua samples.
• Analysis of gene expression related to metabolite transport and signaling in fetal tissues.
• Single-cell transcriptomic analysis of second-trimester intestinal tissue.

Main Results:

• Microbiome-associated metabolites found in fetal intestines are also present in placental tissue.
• Abundance of these metabolites differs across fetal and maternal compartments.
• Gene expression for metabolite transport and signaling is detectable in utero.
• Fetal gastrointestinal and maternal decidua samples show high correlation in metabolite abundance.

Conclusions:

• Microbiome-associated metabolites are maternally derived and vertically transmitted.
• These metabolites, including short-chain fatty acids and secondary bile acids, are biologically active.
• They likely regulate the fetal immune system and prepare the gut for postnatal microbial colonization.