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. 2025 Dec;17(1):2542375.
doi: 10.1080/19490976.2025.2542375. Epub 2025 Aug 6.

Aging: a possible road toward gut microbiota pathoadaptation

Affiliations

Aging: a possible road toward gut microbiota pathoadaptation

Rita Melo-Miranda et al. Gut Microbes. 2025 Dec.

Abstract

Laboratory-raised mice live approximately seven times longer and healthier lives compared to their wild counterparts, due to a standardized healthy diet and limited exposure to environmental stressors. Aging is associated with increased inflammation and microbial dysbiosis. Collectively, these influence microbiota evolution and may contribute to the enrichment in pathobiont frequency observed in old age. Alternatively, this increase could stem from a decline in colonization resistance, creating favorable conditions for pathobiont invasion. Here, we sought to test whether aging in healthy, controlled conditions, could prevent the selection of age-associated pathobionts. We have followed the adaptive evolution of a commensal strain of Escherichia coli in the guts of mice of advanced age and found that it acquired several mutations common to bacteria colonizing young mice, which were absent in old animals. This, together with the increase in Akkermansia muciniphila in mice of advanced age, suggest healthy aging. However, mutations acquired exclusively in the older were mainly pathoadaptive, tuning the metabolism to oxygen and iron availability, hypermotility, and biofilm formation.

Keywords: Aging; Escherichia coli; experimental evolution; microbiota; pathoadaptation.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Age-associated changes in the host and gut microbiota composition before and after treatment with streptomycin and E. coli colonization.
Figure 2.
Figure 2.
The genomic landscape of E. coli evolution across ages.
Figure 3.
Figure 3.
The aged gut favors the emergence of traits associated with hypermotility and adhesion.
Figure 4.
Figure 4.
The gut metabolic profile of young, old and very old mice before and after streptomycin treatment and colonization.

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