Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain

Parker, Aimée, Romano, Stefano, Ansorge, Rebecca, Aboelnour, Asmaa, Le Gall, Gwenaelle ORCID: https://orcid.org/0000-0002-1379-2196, Savva, George M., Pontifex, Matthew G. ORCID: https://orcid.org/0000-0003-2174-2313, Telatin, Andrea, Baker, David, Jones, Emily, Vauzour, David ORCID: https://orcid.org/0000-0001-5952-8756, Rudder, Steven, Blackshaw, L. Ashley, Jeffery, Glen and Carding, Simon R. (2022) Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain. Microbiome, 10. ISSN 2049-2618

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Background: Altered intestinal microbiota composition in later life is associated with inflammaging, declining tissue function, and increased susceptibility to age-associated chronic diseases, including neurodegenerative dementias. Here, we tested the hypothesis that manipulating the intestinal microbiota influences the development of major comorbidities associated with aging and, in particular, inflammation affecting the brain and retina. Methods: Using fecal microbiota transplantation, we exchanged the intestinal microbiota of young (3 months), old (18 months), and aged (24 months) mice. Whole metagenomic shotgun sequencing and metabolomics were used to develop a custom analysis workflow, to analyze the changes in gut microbiota composition and metabolic potential. Effects of age and microbiota transfer on the gut barrier, retina, and brain were assessed using protein assays, immunohistology, and behavioral testing. Results: We show that microbiota composition profiles and key species enriched in young or aged mice are successfully transferred by FMT between young and aged mice and that FMT modulates resulting metabolic pathway profiles. The transfer of aged donor microbiota into young mice accelerates age-associated central nervous system (CNS) inflammation, retinal inflammation, and cytokine signaling and promotes loss of key functional protein in the eye, effects which are coincident with increased intestinal barrier permeability. Conversely, these detrimental effects can be reversed by the transfer of young donor microbiota. Conclusions: These findings demonstrate that the aging gut microbiota drives detrimental changes in the gut–brain and gut–retina axes suggesting that microbial modulation may be of therapeutic benefit in preventing inflammation-related tissue decline in later life.

Item Type: Article
Additional Information: Data Availability: The metagenomic sequencing raw reads generated during this study are freely available at SRA (https://www.ncbi.nlm.nih.gov/sra/) under accession number PRJNA706366. Code: The R code generated to analyze the metabolomic and metagenomic data in this study is available at https://github.com/StfnRomano/Parker_et_al_Inflammaging. Funding Information: The authors gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council (BBSRC); this research was funded by BBSRC Core Capability Grant BB/CCG1860/1, project grant BB/N000250/1, and BBSRC Institute Strategic Programme Grant Gut Microbes and Health (BB/R012490/1) and its constituent projects BBS/E/F/000PR10353, BBS/E/F/000PR10355, and BBS/E/F/000PR10356.
Uncontrolled Keywords: aging,fecal microbiota transplantation,gut–brain axis,gut–retina,inflammaging,intestine,leaky gut,microbiota,microbiology,microbiology (medical) ,/dk/atira/pure/subjectarea/asjc/2400/2404
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
Faculty of Medicine and Health Sciences > School of Health Sciences
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
Faculty of Science > Research Groups > Norwich Epidemiology Centre
Faculty of Medicine and Health Sciences > Research Groups > Norwich Epidemiology Centre
Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging
Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
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Depositing User: LivePure Connector
Date Deposited: 06 May 2022 03:56
Last Modified: 25 Aug 2023 07:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/84886
DOI: 10.1186/s40168-022-01243-w

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