1. Systems biology elucidates the distinctive metabolic niche filled by the human gut microbe Eggerthella lenta.
- Author
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Noecker C, Sanchez J, Bisanz JE, Escalante V, Alexander M, Trepka K, Heinken A, Liu Y, Dodd D, Thiele I, DeFelice BC, and Turnbaugh PJ
- Subjects
- Humans, Mice, Animals, Systems Biology, Ecosystem, Gastrointestinal Microbiome, Actinobacteria metabolism
- Abstract
Human gut bacteria perform diverse metabolic functions with consequences for host health. The prevalent and disease-linked Actinobacterium Eggerthella lenta performs several unusual chemical transformations, but it does not metabolize sugars and its core growth strategy remains unclear. To obtain a comprehensive view of the metabolic network of E. lenta, we generated several complementary resources: defined culture media, metabolomics profiles of strain isolates, and a curated genome-scale metabolic reconstruction. Stable isotope-resolved metabolomics revealed that E. lenta uses acetate as a key carbon source while catabolizing arginine to generate ATP, traits which could be recapitulated in silico by our updated metabolic model. We compared these in vitro findings with metabolite shifts observed in E. lenta-colonized gnotobiotic mice, identifying shared signatures across environments and highlighting catabolism of the host signaling metabolite agmatine as an alternative energy pathway. Together, our results elucidate a distinctive metabolic niche filled by E. lenta in the gut ecosystem. Our culture media formulations, atlas of metabolomics data, and genome-scale metabolic reconstructions form a freely available collection of resources to support further study of the biology of this prevalent gut bacterium., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: P.J.T. is on the scientific advisory boards for Pendulum, Seed, and SNIPRbiome; there is no direct overlap between the current study and these consulting duties. D.D. is a co-founder of Federation Bio, a company developing microbiome-based therapeutics. All other authors have no relevant declarations., (Copyright: © 2023 Noecker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
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