Aging Microbiome Produces Fewer Vital Metabolites
New research illustrates how the gut microbiome influences aging in its host.
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The gut microbiome – a complex ecosystem of millions of bacteria, fungi and other microorganisms that populate the intestine – is known to change as its host ages and may even influence the aging process.
A study from Kiel University has outlined the metabolic changes associated with the aging microbiome using a combination of computational modeling and metagenomics, transcriptomics and metabolomics analyses from the intestines, brain, liver and stool of mice in different age groups.1
By using computer models for each mouse to reflect both the host’s organs and its microbiome, the researchers were able to investigate the molecules exchanged between the host and the microbiome.
They discovered that the host uses the microbiome as a “recycling center” to form useful substances from metabolic end products, but as the host ages, this process slows down.
This decreasing metabolic activity is driven by reduced beneficial interactions between bacterial species as competition for resources increases.
“These changes coincided with increased systemic inflammation and the downregulation of essential host pathways,” the researchers from Kiel University report in their paper, published in Nature Microbiology.
Can age-related microbiome changes be reversed?
Many cellular functions, including nucleotide metabolism, cellular replication and homeostasis, rely on the microbiome and are therefore affected by the metabolic changes to the microbiome as it ages.
In a separate study, the researchers aimed to identify whether the age-related changes to the microbiome could be reversed by performing regular stool transfers from young mice into a cohort of mice over two years.2 As a control, another group of mice regularly received stool transplants from mice of the same age.
In the mice that received transplants from young mice, there were fewer pro-inflammatory factors in the microbiome, and in the mice themselves, there were decreased signs of inflammaging.
Inflammaging
Inflammaging refers to chronic, low-grade inflammation associated with aging that contributes to the development of age-related disease.
These results indicate how the microbiome influences aging in the host and illustrate how targeting the microbiome could offer a therapeutic avenue to improve metabolic health during aging.
References:
1. Best L, Dost T, Esser D, et al. Metabolic modelling reveals the aging-associated decline of host–microbiome metabolic interactions in mice. Nat Microbiol. 2025;10(4):973-991. doi: 10.1038/s41564-025-01959-z
2. Sommer F, Bernardes JP, Best L, et al. Life-long microbiome rejuvenation improves intestinal barrier function and inflammaging in mice. Microbiome. 2025;13(1):91. doi: 10.1186/s40168-025-02089-8
