SummaryCharacterizing trajectories of the composition and function of hominid gut microbiota across diverse environments and host species can help reveal specific properties of the human microbiota, with possible implications for host evolution and health. Using shotgun metagenomic sequencing, we investigated taxonomic and functional diversity in the gut microbiota of wild-living great apes, including two gorilla subspecies (Gorilla gorilla gorilla, Gorilla beringei beringei), three chimpanzee subspecies (Pan troglodytes verus, P.t. troglodytes, P.t. schweinfurthii), and bonobos (Pan paniscus), together with human samples from Africa and Europe. We identified microbial taxonomic and functional adaptations convergent with host phylogeny at both the community and microbial genomic levels. We could show that repeated horizontal gene transfer and gene loss are processes involved in these adaptations. We hypothesize, that these adaptation processes and changes in the microbiome predispose the host to chronic inflammatory disorders, such as type 2 diabetes via altered histidine metabolism and inflammatory bowel disease indicated by adaptation of microbes to aerobic conditions. Additionally, we find multiple lines of evidence suggesting a widespread loss of microbial diversity and evolutionary conserved clades in the human microbiota, especially in the European population. Lastly, we observed patterns consistent with codivergence of hosts and microbes, particularly for the bacterial familyDialisteraceae, though we find that overall, co-phylogeny patterns are frequently disrupted in humans.
Bullous pemphigoid (BP) is an autoimmune skin blistering disease afflicting mostly the elderly and is associated with significantly increased mortality. Here, we conducted the most extensive sampling effort of skin microbiota in BP to date to analyze whether intra-individual, body-site-specific, and/or geographical variation contributes to the emergence of BP. We find marked differences in the skin microbiota of BP patients compared to that of control subjects, and moreover that disease status rather than skin biogeography governs the skin microbiota composition in BP. Our data reveal a discernible transitional stage between normal and diseased skin in BP characterized by a loss of protective microbiota and an increase in sequences matching Staphylococcus aureus, a known inflammation-promoting species. Notably, S. aureus is ubiquitously associated with disease status, suggesting that this taxon is an important indicator of BP. Importantly, differences in a few key indicator taxa are able to reliably discriminate between BP patients and controls, characterized by their opposing abundance patterns. This may serve as valuable information for assessing disease risk and treatment outcomes. Future research will focus on the functional analysis of host-microbe and microbe-microbe interactions and the relevance of the host genome for microbiota abundances to identify novel BP treatment approaches.
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