Biological Sciences Division
Published May 16, 2025 | Version v1
Journal article Open

Microbes with higher metabolic independence are enriched in human gut microbiomes under stress

Creators

  • 1. University of Chicago
  • 2. Stanford University
  • 3. University of Bremen
  • 4. University of Washington
  • 5. Toyota Technological Institute at Chicago
  • 6. University of Copenhagen

Description

A wide variety of human diseases are associated with loss of microbial diversity in the human gut, inspiring a great interest in the diagnostic or therapeutic potential of the microbiota. However, the ecological forces that drive diversity reduction in disease states remain unclear, rendering it difficult to ascertain the role of the microbiota in disease emergence or severity. One hypothesis to explain this phenomenon is that microbial diversity is diminished as disease states select for microbial populations that are more fit to survive environmental stress caused by inflammation or other host factors. Here, we tested this hypothesis on a large scale, by developing a software framework to quantify the enrichment of microbial metabolisms in complex metagenomes as a function of microbial diversity. We applied this framework to over 400 gut metagenomes from individuals who are healthy or diagnosed with inflammatory bowel disease (IBD). We found that high metabolic independence (HMI) is a distinguishing characteristic of microbial communities associated with individuals diagnosed with IBD. A classifier we trained using the normalized copy numbers of 33 HMI-associated metabolic modules not only distinguished states of health vs IBD, but also tracked the recovery of the gut microbiome following antibiotic treatment, suggesting that HMI is a hallmark of microbial communities in stressed gut environments.

Data availability

Accession numbers for publicly available data are listed in our Supplementary Tables that are also accessible at https://doi.org/10.6084/m9.figshare.22679080.

Anvi'o contigs databases of our assemblies for the 408 deeply-sequenced metagenomes, as well as assemblies of the Palleja et al. 2018 metagenomes are available at https://doi.org/10.5281/zenodo.7897987.

Finally, the URL https://doi.org/10.5281/zenodo.7883421 gives access to anvi'o contigs databases for the 338 Genome Taxonomy Database (GTDB) reference genomes that represent populations that are prevalent in human gut metagenomes.

The following data sets were generated:

Veseli I Eren AM (2024) Figshare Supplementary Tables for Veseli et al. 2023. https://doi.org/10.6084/m9.figshare.22679080

Veseli I (2023) Zenodo Palleja et al. 2018 Metagenome Assemblies for Veseli et al. 2023. https://doi.org/10.5281/zenodo.7897987

Veseli I (2023) Zenodo GTDB Genome Contigs DBs for Veseli et al. 2023. https://doi.org/10.5281/zenodo.7883421

The following previously published data sets were used:

Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S (2012) NCBI Sequence Read Archive ID SRA050230. A metagenome-wide association study of gut microbiota in type 2 diabetes. https://www.ncbi.nlm.nih.gov/sra?term=SRA050230

Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, Falony G, Almeida M (2013) EBI European Nucleotide Archive ID PRJEB4336. Richness of human gut microbiome correlates with metabolic markers. https://www.ebi.ac.uk/ena/browser/view/PRJEB4336

Feng Q, Liang S, Jia H, Stadlmayr A, Tang L, Lan Z, Zhang D (2015) EBI European Nucleotide Archive ID PRJEB7774. Gut microbiome development along the colorectal adenoma-carcinoma sequence. https://www.ebi.ac.uk/ena/browser/view/PRJEB7774

Franzosa EA, Sirota-Madi A, Avila-Pacheco J, Fornelos N, Haiser HJ, Reinker S, Vatanen T (2019) NCBI BioProject ID PRJNA400072. Gut microbiome structure and metabolic activity in inflammatory bowel disease. https://www.ncbi.nlm.nih.gov/bioproject/PRJNA400072

Lloyd-Price J, Arze C, Ananthakrishnan AN, Schirmer M, Pacheco JA, Poon TW, Andrews E (2019) NCBI BioProject ID PRJNA398089. Longitudinal Multi'omics of the Human Microbiome in Inflammatory Bowel Disease. https://www.ncbi.nlm.nih.gov/bioproject/PRJNA398089

Parks DH, Chuvochina M, Rinke C, Mussig AJ, Chaumeil PA, Hugenholtz P (2022) GTDB ID release95.0. GTDB: an ongoing census of bacterial and archaeal diversity through a phylogenetically consistent, rank normalized and complete genome-based taxonomy. https://gtdb.ecogenomic.org/

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Additional details

Identifiers

DOI
10.7554/eLife.89862.3
Other
oai:uchicago.tind.io:15468

Funding

National Science Foundation
Graduate Research Fellowship Program
National Institutes of General Medical Sciences
R35 GM133420
Stanford University
Data Science Postdoctoral Fellowship
National Institutes of Health
R35 GM128716
University of Chicago
International Student Fellowship
National Institutes of Health
RC2 DK122394

UChicago Information

Division(s)
Biological Sciences Division
Department(s)
Biophysical Sciences, Medicine, Microbiology