Variations in blood microbiome and LPS concentration inform disease susceptibility differences in primates

Differential exposure to microorganisms over time has contributed to the evolution of primate immune system and its resident microbiota. Since blood is an important immune compartment containing high density of professional immune cells, its microbiome may help explain the divergence of human immune responses from non-human primates (NHPs). The NHP blood microbiota, however, remains uncharacterized and its relationship to blood immune functions are unknown. Here, we aim to characterize primate blood microbiome, its association with inter-species differences in immune phenotypes such as lipopolysaccharide (LPS) sensitivity and infectious disease manifestations. We compare blood microbiome, LPS levels and transcriptomes in four major primate groups [apes, African & Asian monkeys, South American monkeys, strepsirrhines] to assess the role of their variations on observed immune susceptibility differences in primates. Our results show a connection between blood LPS concentrations and known species-specific susceptibilities and stark differences in blood bacterial composition and expression of genes that are important in primate immunity. As expected by their higher LPS susceptibility, humans had the lowest LPS concentrations compared with NHPs. Genes important in LPS responses, e.g. IRAK1, IRF7, Map Kinases and TGF-beta were at least two times more highly expressed in humans compared to macaque, a more resistant species. Our data further provides evidence that many blood microbes are probably mainly sourced from the gut and continuously and selectively leak in to the circulation. Overall, our results provide evidence of a link between the evolution of primate immunity and blood microbiota, possibly affecting disease susceptibility differences.