Best Lena, Dost Thomas, Esser Daniela, Flor Stefano, Gamarra Andy Mercado, Haase Madlen, 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
Research Group Medical Systems Biology, Institute of Experimental Medicine, Kiel University and University Hospital Schleswig-Holstein, Kiel, Germany.
Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/Lübeck, Germany.
Nat Microbiol. 2025 Apr;10(4):973-991. doi: 10.1038/s41564-025-01959-z. Epub 2025 Mar 26.
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.
衰老伴随着肠道微生物群的显著变化，但驱动衰老的分子机制以及微生物群的作用仍不清楚。在这里，我们将衰老小鼠的宏基因组学、转录组学和代谢组学与代谢模型相结合，以表征衰老过程中宿主与微生物群的相互作用。通过重建宿主和181种小鼠肠道微生物的综合代谢模型，我们发现宿主代谢对已知和先前未描述的微生物相互作用存在复杂的依赖性。我们观察到衰老微生物群内的代谢活性显著降低，同时细菌物种之间的有益相互作用减少。这些变化与全身炎症增加和宿主关键途径的下调同时发生，特别是在核苷酸代谢方面，预计该途径依赖于微生物群，对维持肠道屏障功能、细胞复制和体内平衡至关重要。我们的结果阐明了可能影响宿主衰老过程的微生物群与宿主的相互作用。这些途径可能成为未来基于微生物群的抗衰老疗法开发的靶点。
