The cynomolgus macaque, Macaca fascicularis, is a non-human primate (NHP) widely used in biomedical research as its genetics, immunology and physiology are similar to those of humans. They may also be a useful model of the intestinal microbiome as their prokaryome resembles that of humans. However, beyond the prokaryome relatively little is known about other constituents of the macaque intestinal microbiome including the mycobiome. Here, we conducted a region-by-region taxonomic survey of the cynomolgus intestinal mycobiota, from duodenum to distal colon, of sixteen captive animals of differing age (from young to old). Using a high-throughput ITS1 amplicon sequencing-based approach, the cynomolgus gut mycobiome was dominated by fungi from the Ascomycota phylum. The budding yeast genus Kazachstania was most abundant, with the thermotolerant species K. pintolopesii highly prevalent, and the predominant species in both the small and large intestines. This is in marked contrast to humans, in which the intestinal mycobiota is characterised by other fungal genera including Candida and Saccharomyces, and Candida albicans. This study provides a comprehensive insight into the fungal communities present within the captive cynomolgus gut, and for the first time identifies K. pintolopesii as a candidate primate gut commensal.

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.

Kazachstania pintolopesii is an opportunistic mammalian pathobiont from the K. telluris species complex. No draft genomes of this species are currently available. Here, we report the first draft genome sequence of a primate isolate of K. pintolopesii (NCYC 4417).

The cynomolgus macaque, Macaca fascicularis, is a non-human primate (NHP) widely used in biomedical research as it shares behavioural, genetic, immunological and physiological similarities with humans. These similarities may extend to the enteric microbiome, with some microbial taxa common to both humans and NHPs. However, to date, the majority of these microbial surveys have focused on the prokaryome, and have largely ignored or overlooked the NHP gut mycobiome. To address this shortfall, we have undertaken a region-by-region taxonomic survey of the cynomolgus intestinal mycobiota, from duodenum to distal colon, of ten captive animals of differing age. Using a high-throughput ITS1 amplicon sequencing-based approach, we found that fungi from the Ascomycota phylum dominate the cynomolgus enteric mycobiota. The budding yeast genus Kazachstania was most abundant, with K. pintolopesii and K. telluris highly prevalent, and the predominant species in many of the intestinal samples. However, while K. pintolopesii was present throughout the primate GI tract, K. telluris was found mainly in the small intestine. In this study, K. pintolopesii was identified as the dominant enteric fungus in captive cynomolgus macaques. This contrasts with humans, where Candida albicans is a common member of the intestinal microbiota. To our knowledge, this is the first time K. pintolopesii has been identified as a primate gut commensal.