Centers and Institutes
Published April 17, 2023 | Version v1
Journal article Open

Metabolic independence drives gut microbial colonization and resilience in health and disease

Creators

  • 1. University of Chicago
  • 2. University of Calgary
  • 3. Lurie Children's Hospital of Chicago
  • 4. Earlham Institute
  • 5. Toyota Technological Institute at Chicago
  • 6. Konya Food and Agriculture University
  • 7. University of Alberta

Description

Background: Changes in microbial community composition as a function of human health and disease states have sparked remarkable interest in the human gut microbiome. However, establishing reproducible insights into the determinants of microbial succession in disease has been a formidable challenge.

Results: Here we use fecal microbiota transplantation (FMT) as an in natura experimental model to investigate the association between metabolic independence and resilience in stressed gut environments. Our genome-resolved metagenomics survey suggests that FMT serves as an environmental filter that favors populations with higher metabolic independence, the genomes of which encode complete metabolic modules to synthesize critical metabolites, including amino acids, nucleotides, and vitamins. Interestingly, we observe higher completion of the same biosynthetic pathways in microbes enriched in IBD patients.

Conclusions: These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of "dysbiosis" that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.

Data availability

Raw sequencing data for donor and recipient metagenomes are stored under the NCBI BioProject PRJNA701961 (see Additional file 1 for accession numbers for each sample). The geographically distributed human gut metagenomes were obtained from previously published datasets (Additional file 5). The URL https://merenlab.org/data/fmt-gut-colonization serves a reproducible bioinformatics workflow and gives access to ad hoc scripts, usage instructions, and intermediate data objects to reproduce findings in our study. All ad hoc scripts also available under CC-BY 4.0 International license on Figshare (https://doi.org/10.6084/m9.figshare.22352989).

Files

Metabolic-independence-drives-gut-microbial-colonization-and-resilience-in-health-and-disease.pdf

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Additional details

Identifiers

DOI
10.1186/s13059-023-02924-x
Other
oai:uchicago.tind.io:5767

Funding

GI Research Foundation (GIRF)
Mutchnik Family Fund
Robert C. and Mary Jane Gallo Scholarship Fund
Alissa and Gianna Carlino Fellowship in Celiac Disease Research
Cancer Center Support
P30CA014599
Digestive Diseases Research Core Center
P30 DK42086
NIDDK
RC2 DK122394
National Science Foundation
Graduate Research Fellowship

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Medicine, Microbiology
Center(s) or Institute(s)
Marine Biological Laboratory