Age and the microbiota-gut-brain axis: a non-human primate model of human ageing

Purse, Catherine (2024) Age and the microbiota-gut-brain axis: a non-human primate model of human ageing. Doctoral thesis, University of East Anglia.

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Abstract

Age-associated changes to the intestinal microbiome, and its impact on the gut-brain axis, are increasingly being linked to the development of inflammageing and neurodegenerative disease. To study the interactions of the microbiota-gut-brain axis, it is important to find a suitable animal model for studies of human ageing. Here, the impact of ageing on the microbiota-gut-brain axis is assessed in a cohort of healthy, captive-bred cynomolgus macaques of differing ages. Using whole-genome sequencing (WGS) and internal transcribed spacer 1 (ITS1) amplicon sequencing methods, age-associated changes in taxonomic composition and metabolic potential were assessed in multiple spatial regions of the intestine, from duodenum to distal colon. Alpha and beta diversity metrics revealed distinct prokaryotic composition profiles in the small and large intestine, but relative invariance of taxonomy and metabolic potential was observed with age. 108 putative novel prokaryotic genomes were also identified. The predominant fungus in all regions and at all ages was Arxiozyma pintolopesii. Closely related Arxiozyma species have been implicated as potential intestinal pathobionts, however, A. pintolopesii did not appear to exhibit pathogenicity in an in vitro model of the intestinal epithelial barrier. Parallel work in germ-free mice showed that orally delivered Candida albicans, a human pathobiont, can translocate from the gut to the brain, inducing an inflammatory response. Accumulation of age-associated brain pathology, including iron deposition in the substantia nigra, was observed in cynomolgus macaques ≥13 years. However, this did not correlate with increased microglial cell density, as assessed by ionized calcium binding adaptor molecule 1 (Iba1) expression compared to young animals. Indications of an age-associated increase in systemic inflammation and intestinal permeability were studied via the quantification of blood-based biomarkers and histological examination of intestinal tissue. This work establishes a foundation for further study of the impact of ageing on the microbiota-gut-brain axis in this important animal model.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	Kitty Laine
Date Deposited:	03 Jun 2025 10:49
Last Modified:	03 Jun 2025 10:49
URI:	https://ueaeprints.uea.ac.uk/id/eprint/99383
DOI:

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