Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Physician-Scientist Development
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • In-Press Preview
    • Resource and Technical Advances
    • Clinical Research and Public Health
    • Research Letters
    • Editorials
    • Perspectives
    • Physician-Scientist Development
    • Reviews
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Resource and Technical Advances
  • Clinical Research and Public Health
  • Research Letters
  • Editorials
  • Perspectives
  • Physician-Scientist Development
  • Reviews
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Transfers
  • Advertising
  • Job board
  • Contact
In utero human intestine harbors unique metabolome, including bacterial metabolites
Yujia Li, Jessica M. Toothaker, Shira Ben-Simon, Lital Ozeri, Ron Schweitzer, Blake T. McCourt, Collin C. McCourt, Lael Werner, Scott B. Snapper, Dror S. Shouval, Soliman Khatib, Omry Koren, Sameer Agnihorti, George Tseng, Liza Konnikova
Yujia Li, Jessica M. Toothaker, Shira Ben-Simon, Lital Ozeri, Ron Schweitzer, Blake T. McCourt, Collin C. McCourt, Lael Werner, Scott B. Snapper, Dror S. Shouval, Soliman Khatib, Omry Koren, Sameer Agnihorti, George Tseng, Liza Konnikova
View: Text | PDF
Research Article Gastroenterology Metabolism

In utero human intestine harbors unique metabolome, including bacterial metabolites

  • Text
  • PDF
Abstract

Symbiotic microbial colonization through the establishment of the intestinal microbiome is critical to many intestinal functions, including nutrient metabolism, intestinal barrier integrity, and immune regulation. Recent studies suggest that education of intestinal immunity may be ongoing in utero. However, the drivers of this process are unknown. The microbiome and its byproducts are one potential source. Whether a fetal intestinal microbiome exists is controversial, and whether microbially derived metabolites are present in utero is unknown. Here, we aimed to determine whether bacterial DNA and microbially derived metabolites can be detected in second trimester human intestinal samples. Although we were unable to amplify bacterial DNA from fetal intestines, we report a fetal metabolomic intestinal profile with an abundance of bacterially derived and host-derived metabolites commonly produced in response to microbiota. Though we did not directly assess their source and function, we hypothesize that these microbial-associated metabolites either come from the maternal microbiome and are vertically transmitted to the fetus to prime the fetal immune system and prepare the gastrointestinal tract for postnatal microbial encounters or are produced locally by bacteria that were below our detection threshold.

Authors

Yujia Li, Jessica M. Toothaker, Shira Ben-Simon, Lital Ozeri, Ron Schweitzer, Blake T. McCourt, Collin C. McCourt, Lael Werner, Scott B. Snapper, Dror S. Shouval, Soliman Khatib, Omry Koren, Sameer Agnihorti, George Tseng, Liza Konnikova

×

Figure 4

Differential expression of individual metabolites and metabolic pathways.

Options: View larger image (or click on image) Download as PowerPoint
Differential expression of individual metabolites and metabolic pathways...
(A) Tree map of differentially expressed subpathways between fetal and pediatric intestines. Numbers correspond to pathways described in Supplemental Table 1. Darker shades and black numbers indicate statistically significant differentially expressed pathways using Fisher’s exact test (P < 0.1). (B) Integrated pathway analysis for differentially expressed pathways between fetal and pediatric samples. Bar length is indicative of more significant q value. Numbers on right-hand side correlate to tree map pathways in Supplemental Table 1. (C) Heatmap of differential expression of individual metabolites. Each column represents one sample and each row represents one metabolite. For a complete list of metabolites, see Supplemental Table 5. (D) Volcano plot of differentially expressed metabolites between fetal and pediatric samples. Metabolites with positive x axis are those with higher expression in fetus. The 8 most significant metabolites are labeled with the metabolite name. All significant differentially expressed metabolites (q < 0.05) are color-coded by superpathway from A. (E) Top 20 metabolites from elastic net model. Red asterisk indicates metabolite from media.

Copyright © 2025 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts