Systems biology elucidates the distinctive metabolic niche filled by the human gut microbe Eggerthella lenta
Open Access
- 19 May 2023
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Biology
- Vol. 21 (5), e3002125
- https://doi.org/10.1371/journal.pbio.3002125
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.Funding Information
- National Institutes of Health (2R01HL122593; 1R01AT011117; 1R01DK114034)
- National Institutes of Health (F32GM140808)
- National Institute of Allergy and Infectious Diseases (T32AI060537)
- National Institute of General Medical Sciences (T32GM141323)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK110335)
- National Institute of General Medical Sciences (R35GM142873)
- National Center for Complementary and Alternative Medicine (R01AT011396)
- National Institute on Aging (1RF1AG058942 and 1U19AG063744)
- National Institute of General Medical Sciences (R25GM056847)
- National Science Foundation (1650113)
- Chan Zuckerberg Biohub – San Francisco (7028823)
- Burroughs Wellcome Fund (1017921)
- Stanford Microbiome Therapies Initiative
- OHF-ASN Foundation for Kidney Research Career Development Award
- European Research Council under the European Union’s Horizon 2020 research and innovation programme (757922)
- Science Foundation Ireland (12/RC/2273-P2)
This publication has 103 references indexed in Scilit:
- Agmatine: clinical applications after 100 years in translationDrug Discovery Today, 2013
- Focused Review: Agmatine in Fermented FoodsFrontiers in Microbiology, 2012
- Proteinortho: Detection of (Co-)orthologs in large-scale analysisBMC Bioinformatics, 2011
- The Chemical Translation Service—a web-based tool to improve standardization of metabolomic reportsBioinformatics, 2010
- Systems-Level Metabolic Flux Profiling Elucidates a Complete, Bifurcated Tricarboxylic Acid Cycle in Clostridium acetobutylicumJournal of Bacteriology, 2010
- A protocol for generating a high-quality genome-scale metabolic reconstructionNature Protocols, 2010
- Development of Chemically Defined Media Supporting High-Cell-Density Growth of Lactococci, Enterococci, and StreptococciApplied and Environmental Microbiology, 2009
- Diversity in enoyl-acyl carrier protein reductasesCellular and Molecular Life Sciences, 2009
- The Gene Cluster for Agmatine Catabolism ofEnterococcus faecalis: Study of Recombinant Putrescine Transcarbamylase and Agmatine Deiminase and a Snapshot of Agmatine Deiminase Catalyzing Its ReactionJournal of Bacteriology, 2007
- Comparative genomics of bacterial and plant folate synthesis and salvage: predictions and validationsBMC Genomics, 2007