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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.*

Metabolic modelling reveals the aging-associated decline of host-microbiome metabolic interactions in mice.

Nat. Microbiol., DOI: 10.1038/s41564-025-01959-z (2025)
DOI PMC
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Gut Microbiome; Growth Dynamics; Dna-damage; Disease; Health; Age; Physiology; Networks
ISSN (print) / ISBN 2058-5276
e-ISSN 2058-5276
Zeitschrift Nature microbiology
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit BioGeoChemistry and Analytics (BGC)
Förderungen Kiel University
Carl Zeiss Foundation IMPULS programme
European Union's Horizon 2020 Research and Innovation Programme (under the Marie Sklodowska-Curie grant
BMBF iTREAT

German Research Foundation