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PreprintCited by 80Gut microbiota and healthMicrobial Fuel Cells and BioremediationBacterial Genetics and Biotechnology

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Dietary- and host-derived metabolites are used by diverse gut bacteria for anaerobic respiration

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Little, Alexander S., Younker, Isaac T., Schechter, Matthew S., Bernardino, Paola Nol, Méheust, Raphaël, Stemczynski, Joshua, Scorza, Kaylie, Mullowney, Michael W., Sharan, Deepti, Waligurski, Emily, Smith, Rita, Ramanswamy, Ramanujam, Leiter, William, Moran, David, McMillin, Mary, Odenwald, Matthew A., Iavarone, Anthony T., Sidebottom, Ashley M., Sundararajan, Anitha, Pamer, Eric G., Eren, Murat A., Light, Samuel H.·2022·Nature Microbiology
DOI 10.1101/2022.12.26.521950PMC PMC11055453

Preprint — published as 10.1038/s41564-023-01560-2 · Paper page

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Abstract

Respiratory reductases enable microbes to utilize molecules present in anaerobic ecosystems as energy-generating respiratory electron acceptors. Here we identify three taxonomically distinct families of human gut bacteria (Burkholderiaceae, Eggerthellaceae, Erysipelotrichaceae) that encode large arsenals of tens-to-hundreds of respiratory-like reductases per genome. Screening species from each family ( Sutterella wadsworthensis , Eggerthella lenta , and Holdemania filiformis ), we discover 22 metabolites used as respiratory electron acceptors in a species-specific manner. Identified reactions transform multiple classes of dietary- and host-derived metabolites, including bioactive molecules resveratrol and itaconate. Products of identified respiratory metabolisms highlight poorly characterized compounds, such as the itaconate-derived 2-methylsuccinate. Reductase substrate-profiling defines enzyme-substrate pairs and reveals a complex picture of reductase evolution, providing evidence that reductases with specificities for related cinnamate substrates independently emerged at least four times. These studies thus establish an exceptionally versatile form of anaerobic respiration that directly links microbial energy metabolism to the gut metabolome.

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Metadata

Authors
Little, A. S., Younker, I. T., Schechter, M. S., Bernardino, P. N., Méheust, R., Stemczynski, J., Scorza, K., Mullowney, M. W., Sharan, D., Waligurski, E., Smith, R., Ramanswamy, R., Leiter, W., Moran, D., McMillin, M., Odenwald, M. A., Iavarone, A. T., Sidebottom, A. M., Sundararajan, A., Pamer, E. G., Eren, M. A., & Light, S. H.
Affiliations
  • University of Chicago (US)
  • Centre National de la Recherche Scientifique (FR)
  • University of California, Berkeley (US)
Corresponding author
Light, Samuel H.
ORCID
Venue
Nature Microbiology
Publisher
openRxiv
Published
2022-12-27
Volume
9
Issue
1
Pages
55-69
ISSN
2058-5276 (ISSN-L)
DOI
10.1101/2022.12.26.521950
PMC
PMC11055453
OpenAlex
W4390587924
Cited by
80
References
1
Citations by year
2026: 27 · 2025: 30 · 2024: 21 · 2023: 2
FWCI
10.59
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Nature Microbiology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Helmholtz-Zentrum für Polar-und Meeresforschung (Alfred-Wegener-Institut) (submittedVersion)
Funders
  • U.S. Department of Health and Human Services (1S10OD020062-01, K22AI144031 &amp, T32DK007074, R35GM146969)
  • Kinship Foundation
  • Searle Scholars Program
  • National Institutes of Health (1s10od020062-01)
  • National Institute of General Medical Sciences (R35GM146969)
  • National Institute of Allergy and Infectious Diseases (K22AI144031)
  • National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007074, P30DK020595)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Physical Sciences › Environmental Science › Environmental Engineering › Microbial Fuel Cells and Bioremediation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
anaerobic respiration, gut microbiota, Burkholderiaceae, Eggerthella, Erysipelotrichaceae, Sutterella wadsworthensis, Eggerthella lenta, dietary metabolites, resveratrol, itaconate, gut metabolome
MeSH terms
Anaerobiosis, Bacteria, Humans, Oxidoreductases, Respiration, Succinates, Ecosystem

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