Aging: a possible road toward gut microbiota pathoadaptation

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

ESCHERICHIA-COLI; BIOFILM FORMATION; ADAPTATION; MOTILITY; FLAGELLA; LRHA; CHEMOTAXIS; EXPRESSION; REGULATOR; EVOLUTION

subject category

Gastroenterology & Hepatology; Microbiology

authors

Melo-Miranda, R; Pinto, A; Barreto, HC; Jesus, CSH; Gordo, I; Duarte, IF; Sousa, A

our authors

acknowledgements

This work was funded by Fundac & atilde;o paraa Ciencia e Tecnologia [PTDC/BIAEVL/30212/2017] ("MicroAgeing-the role of themicrobiota in ageing"), and Programa Operacional Regional do Centro, through Fundo Europeu de Desenvolvimento Regional-FEDER [CENTRO-01-0145-FEDER-030212], and by FCT-Fundac & atilde;o para a Ciencia e Tecnologia, I.P. by project reference [UID 4501] - Instituto de Biomedicina-Aveiro.R. M-M. was supported by the individual Grant [2020.05130.BD] (DOI identifier: https://doi.org/10.54499/2020.05130.BD) from FCT.H.C.B. was supported by the DREAM [ANR-20-AMR-0002] grant, and by the [HORIZON-MSCA-2023-PF-01] project number [101148351]- MICROINVADER, funded by the European Union. Views and opinions expressed are however those of the authoronly and do not necessarily reflect those of the European Union or the European Research Executive Agency. This work was also supported by grant [ERC-2022-ADG 101096203] EvoInHi toI.G., funded by the European Union. Views and opinions expressed are however those of the authors only and do not necessarily reflect those of the European Union or ERC. Neither the European Union nor the granting authority can be held responsible for them.This work was also supported by CICECO-AveiroInstitute of Materials [UIDB/50011/2020, DOI 10.54499/UIDB/50011/2020;UIDP/50011/2020, DOI 10.54499/UIDP/50011/2020 & LA/P/0006/2020, DOI 10.54499/LA/P/0006/2020], and [UID/50006]- LaboratorioAssociado para a Quimica Verde-Tecnologias e Processos Limpos (LAQV-REQUIMTE), financed through national funds through FCT/MCTES (PIDDAC). FCT is also acknowledged for the research contract under the Scientific Employment Stimulus to I.F.D.[CEECIND/02387/2018]. The NMR spectrometer is part of the National NMR Network (PTNMR) and is partially supported by Infrastructure Project N degrees 022161.A.S. was funded by FCT through Scientific Employment Stimulus (reference [CEECINST/00026/2018/CP1521/CT0001] and DOI identifier https://doi.org/10.54499/CEECINST/00026/2018/CP1521/CT0001).

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