Metabolic modelling reveals the aging-associated decline of host–microbiome metabolic interactions in mice
Open accessPublished version of a preprint
Abstract
Aging is accompanied by considerable changes in the gut microbiome, yet the molecular mechanisms driving aging and the role of the microbiome remain unclear. Here we combined metagenomics, transcriptomics and metabolomics from aging mice with metabolic modelling to characterize host–microbiome interactions during aging. Reconstructing integrated metabolic models of host and 181 mouse gut microorganisms, we show a complex dependency of host metabolism on known and previously undescribed microbial interactions. We observed a pronounced reduction in metabolic activity within the aging microbiome accompanied by reduced beneficial interactions between bacterial species. These changes coincided with increased systemic inflammation and the downregulation of essential host pathways, particularly in nucleotide metabolism, predicted to rely on the microbiota and critical for preserving intestinal barrier function, cellular replication and homeostasis. Our results elucidate microbiome–host interactions that potentially influence host aging processes. These pathways could serve as future targets for the development of microbiome-based anti-aging therapies.
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References 110 · Cited by 65
- Authors
- Best, L., Dost, T., Esser, D., Flor, S., Gamarra, A. M., Haase, M., Kadibalban, A. S., Marinos, G., Walker, A., Zimmermann, J., Simon, R., Schmidt, S., Taubenheim, J., Künzel, S., Häsler, R., Franzenburg, S., Groth, M., Waschina, S., Rosenstiel, P., Sommer, F., Witte, O. W., Schmitt-Kopplin, P., Baines, J. F., Frahm, C., & Kaleta, C.
- Affiliations
- Christian-Albrechts-Universität zu Kiel (DE)
- Jena University Hospital (DE)
- Helmholtz Munich (DE)
- Max Planck Institute for Evolutionary Biology (DE)
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Corresponding author
- Kaleta, Christoph
- ORCID
- Best, Lena
- Dost, Thomas
- Flor, Stefano
- Gamarra, Andy Mercado
- Kadibalban, A. Samer
- Marinos, Georgios
- Walker, Alesia
- Zimmermann, Johannes
- Simon, Rowena
- Schmidt, Silvio
- Taubenheim, Jan
- Künzel, Sven
- Häsler, Robert
- Franzenburg, Sören
- Groth, Marco
- Waschina, Silvio
- Rosenstiel, Philip
- Sommer, Felix
- Witte, Otto W.
- Schmitt-Kopplin, Philippe
- Baines, John F.
- Frahm, Christiane
- Kaleta, Christoph
- Venue
- Nature Microbiology
- Published
- 2025-03-26
- Volume
- 10
- Issue
- 4
- Pages
- 973-991
- ISSN
- 2058-5276 (ISSN-L)
- PMC
- PMC11964932
- OpenAlex
- W4408844321
- Cited by
- 65
- References
- 110
- Citations by year
- 2026: 41 · 2025: 24
- FWCI
- 19.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Microbiology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- Funders
- EC | Horizon 2020 Framework Programme (859890)
- Deutsche Forschungsgemeinschaft (FOR5042, EXC2167, 416 418087534)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- aging, gut microbiota, host-microbiome interactions, metabolic modeling, microbial metabolic interactions, systemic inflammation, nucleotide metabolism, intestinal barrier function, anti-aging therapy, mouse aging
- MeSH terms
- Gastrointestinal Microbiome, Host Microbial Interactions, Aging, Animals, Bacteria, Male, Mice, Inbred C57BL, Mice, Metabolomics, Metagenomics
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