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

Parker, Aimee; Romano, Stefano; Ansorge, Rebecca; Aboelnour, Asmaa; Le Gall, Gwenaelle; Savva, George M; Pontifex, Matthew G; ... Carding, Simon R; + view all (2022) Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain. Microbiome , 10 (1) , Article 68. 10.1186/s40168-022-01243-w. Green open access

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Abstract

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. [MediaObject not available: see fulltext.] Graphical abstract: [Figure not available: see fulltext.]

Type: Article
Title: Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s40168-022-01243-w
Publisher version: https://doi.org/10.1186/s40168-022-01243-w
Language: English
Additional information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Keywords: Science & Technology, Life Sciences & Biomedicine, Microbiology, Aging, Microbiota, Gut-brain axis, Gut-retina, Intestine, Fecal microbiota transplantation, Leaky gut, Inflammaging, FACTOR-H POLYMORPHISM, MACULAR DEGENERATION, MICROGLIA, INFLAMMATION, ASSOCIATIONS, HOMEOSTASIS, ACTIVATION, DISEASE, SYSTEM, EPITHELIUM
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10150438
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