Abstract
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.
Original language | English (US) |
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Article number | 78 |
Journal | Genome biology |
Volume | 24 |
Issue number | 1 |
DOIs | |
State | Published - Dec 2023 |
Funding
We thank Mitchell L. Sogin, Eugene B. Chang, Samuel H. Light, and Howard A. Shuman for helpful discussions, Ryan Moore and Ozcan C. Esen for technical support, and Nicola Segata and the members of the Segata group for their assistance with genomes from healthy gut metagenomes. We also thank Kaiyu Wu, Robyn Louie and Linda Ward of the IPC Research Laboratory at the University of Calgary for their help with patient recruitment and sampling. The review history is available as Additional file 11. Wenjing She was the primary editor of this article and managed its editorial process and peer review in collaboration with the rest of the editorial team. This project was supported by the GI Research Foundation (GIRF) and the Mutchnik Family Fund. Additionally, ARW acknowledges support from the Robert C. and Mary Jane Gallo Scholarship Fund; JF acknowledges support from the Alissa and Gianna Carlino Fellowship in Celiac Disease Research; BJ acknowledges support from the Cancer Center Support grant P30CA014599 and Digestive Diseases Research Core Center P30 DK42086; AME acknowledges support from the NIH NIDDK grant (RC2 DK122394); and IV acknowledges support from the National Science Foundation Graduate Research Fellowship (1746045).
Keywords
- Fecal microbiota transplantation
- Human gut microbiome
- Metabolic independence
- Microbial colonization
- Microbial metabolism
ASJC Scopus subject areas
- Genetics
- Ecology, Evolution, Behavior and Systematics
- Cell Biology