Fecal transplant from vaginally seeded infants decreases intraabdominal adiposity in mice

ABSTRACT

Exposing C-section infants to the maternal vaginal microbiome, coined “vaginal seeding”, partially restores microbial colonization. However, whether vaginal seeding decreases metabolic disease risk is unknown. Therefore, we assessed the effect of vaginal seeding of human infants on adiposity in a murine model. Germ-free mice were colonized with transitional stool from human infants who received vaginal seeding or control (placebo) seeding in a double-blind randomized trial. There was a reduction in intraabdominal adipose tissue (IAAT) volume in male mice that received stool from vaginally seeded infants compared to control infants. Higher levels of isoleucine and lower levels of nucleic acid metabolites were observed in controls and correlated with increased IAAT. This suggests that early changes in the gut microbiome and metabolome caused by vaginal seeding have a positive impact on metabolic health.

GRAPHICAL ABSTRACT

KEYWORDS:

• Vaginal seeding
• vaginal microbiome transfer
• cesarean section
• microbiome
• microbiota
• metabolites
• neonate
• adiposity
• metabolism

Acknowledgments

The authors thank Kristy and Roger Crombie for their generous philanthropic donation toward this project in loving memory of their daughter Anna Charlotte.

The authors thank the Inova Foundation and its donors, including Steve Smith and Christine Luckscheiter, for support of this project.

The authors would like to acknowledge the National Cancer Institute Microbiome Core for performing the sequencing and NIH HPC Biowulf Cluster for providing computational resources.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosure statement

MDB has intellectual property on NYU patent US Patent 10,357,521. NTM is on the scientific advisory board of Tiny Health Inc. CLS has unrelated institutional-based funding from Janssen and Bristol Myers Squibb and receives unrelated royalties from UpToDate for reviewing and authorship. No other authors have competing interests to declare.

Author contributions

Conceptualization: CLS, NTM, SKH

Methodology: HD, SW, SL, CLS, SKJ, NTM, SKH

Investigation: SN, CT, HD, SW, JCD, CRB, AS, EB, BS, MB, QC, SL, MGDB, SKJ, CLS, NTM, SKH

Data Curation: SN, CT, HD, SW, EB, BS, JCD, MB, QC, SL

Visualization: SN, CT, EB, BS

Funding acquisition: CLS, NTM, SKH

Project administration: SL, CLS, SKH

Supervision: CLS, SKH, NTM

Writing – original draft: SN, SKH, NTM

Writing – review & editing: SN, CT, HD, SW, JCD, CRB, AS, EB, BS, MB, QC, SL, MGDB, SKJ, CLS, NTM, SKH

SN and CT are co-first authors. The authorship order was determined by SN also contributing to writing the original draft of the manuscript.

Data availibility

Lead contact

Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact, Suchitra Hourigan ([email protected]).

Materials availability

This study did not generate new unique reagents.

Data and code availability

Sequencing reads are deposited in the Sequence Read Archive (SRA) under submission PRNJA985247, publicly available as of the date of publication. Metabolite data is deposited at https://figshare.com/articles/dataset/Polar_metabolomics_and_Bile_acid_data_for_Namasivayam_2023/23699571.

This paper does not report original code.

Study approval

Human subjects in the study were enrolled under the institutional review board approved study (WCG IRB # 1300043) at the Inova Health System in Northern Virginia under the US Food and Drug Administration IND# 18076. Written informed consent was obtained.

Germ-free mice were housed in the Germ-Free Mice Core at Johns Hopkins University School of Public Health under SOP SP20M233.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2353394

Additional information

Funding

National Institute of Allergy and Infectious Diseases of the National Institutes of Health under the Intramural Research Program (SKH).The Johns Hopkins Clinical Research Network Research Accelerator and Mentorship Program grant (CLS, SKH).National Heart, Lung, and Blood Institute of the National Institutes of Health, (K01HL141589) (NTM).National Heart, Lung, and Blood Institute of the National Institutes of Health, (5K12HL143957) (CT).Emch Fund and C&D Fund, CIFAR (MGDB).