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ToolsParker, Aimée, James, Steve A., Purse, Catherine, Brion, Arlaine, Goldson, Andrew, Telatin, Andrea, Baker, David and Carding, Simon R. (2022) Absence of bacteria permits fungal gut-to-brain translocation and invasion in germfree mice but ageing alone does not drive pathobiont expansion in conventionally raised mice. Frontiers in Aging Neuroscience, 14. ISSN 1663-4365
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Abstract
Age-associated changes in the structure of the intestinal microbiome and in its interaction with the brain via the gut-brain axis are increasingly being implicated in neurological and neurodegenerative diseases. Intestinal microbial dysbiosis and translocation of microbes and microbial products including fungal species into the brain have been implicated in the development of dementias such as Alzheimer’s disease. Using germ-free mice, we investigated if the fungal gut commensal, Candida albicans, an opportunistic pathogen in humans, can traverse the gastrointestinal barrier and disseminate to brain tissue and whether ageing impacts on the gut mycobiome as a pre-disposing factor in fungal brain infection. C. albicans was detected in different regions of the brain of colonised germ-free mice in both yeast and hyphal cell forms, often in close association with activated (Iba-1+) microglial cells. Using high-throughput ITS1 amplicon sequencing to characterise the faecal gut fungal composition of aged and young SPF mice, we identified several putative gut commensal fungal species with pathobiont potential although their abundance was not significantly different between young and aged mice. Collectively, these results suggest that although some fungal species can travel from the gut to brain where they can induce an inflammatory response, ageing alone is not correlated with significant changes in gut mycobiota composition which could predispose to these events. These results are consistent with a scenario in which significant disruptions to the gut microbiota or intestinal barrier, beyond those which occur with natural ageing, are required to allow fungal escape and brain infection.
| Item Type: | Article |
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| Additional Information: | Data Availability Statement: The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, PRJEB49148. 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 and Project Grant: BB/N000250/1), BBSRC Institute Strategic Programme Grant Gut Microbes and Health (BB/R012490/1), and its constituent projects (BBS/E/F/000PR10353 and BBS/E/F/000PR10355). |
| Uncontrolled Keywords: | ageing,candida albicans,dementia,gut-brain,its1 sequencing,mycobiome,pathobiont,ageing,cognitive neuroscience ,/dk/atira/pure/subjectarea/asjc/1300/1302 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | 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 |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 22 Oct 2024 13:30 |
| Last Modified: | 22 Oct 2024 16:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97113 |
| DOI: | 10.3389/fnagi.2022.828429 |
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