Destabilization of the gut microbiome marks the end‐stage of simian immunodeficiency virus infection in wild chimpanzees

Abstract

Enteric dysbiosis is a characteristic feature of progressive human immunodeficiency virus type 1 (HIV-1) infection but has not been observed in simian immunodeficiency virus (SIVmac)-infected macaques, including in animals with end-stage disease. This has raised questions concerning the mechanisms underlying the HIV-1 associated enteropathy, with factors other than virus infection, such as lifestyle and antibiotic use, implicated as playing possible causal roles. Simian immunodeficiency virus of chimpanzees (SIVcpz) is also associated with increased mortality in wild-living communities, and like HIV-1 and SIVmac, can cause CD4+ T cell depletion and immunodeficiency in infected individuals. Given the central role of the intestinal microbiome in mammalian health, we asked whether gut microbial constituents could be identified that are indicative of SIVcpz status and/or disease progression. Here, we characterized the gut microbiome of SIVcpz-infected and -uninfected chimpanzees in Gombe National Park, Tanzania. Subjecting a small number of fecal samples (N = 9) to metagenomic (shotgun) sequencing, we found bacteria of the family Prevotellaceae to be enriched in SIVcpz-infected chimpanzees. However, 16S rRNA gene sequencing of a larger number of samples (N = 123) failed to show significant differences in both the composition and diversity (alpha and beta) of gut bacterial communities between infected (N = 24) and uninfected (N = 26) chimpanzees. Similarly, chimpanzee stool-associated circular virus (Chi-SCV) and chimpanzee adenovirus (ChAdV) identified by metagenomic sequencing were neither more prevalent nor more abundant in SIVcpz-infected individuals. However, fecal samples collected from SIVcpz-infected chimpanzees within 5 months before their AIDS-related death exhibited significant compositional changes in their gut bacteriome. These data indicate that SIVcpz-infected chimpanzees retain a stable gut microbiome throughout much of their natural infection course, with a significant destabilization of bacterial (but not viral) communities observed only in individuals with known immunodeficiency within the last several months before their death.

CHIIMP: An automated high‐throughput microsatellite genotyping platform reveals greater allelic diversity in wild chimpanzees

“…Over the past two decades, microsatellite analyses have been an integral part of studies of wild chimpanzees, providing insight into their evolution, population genetics, behavior, disease association and social structure (Barbian et al, 2018;Becquet, Patterson, Stone, Przeworski, & Reich, 2007;Keele et al, 2009;Langergraber, Mitani, & Vigilant, 2007;Moeller et al, 2016;Rudicell et al, 2010;Santiago et al, 2003;Vigilant, Hofreiter, Siedel, & Boesch, 2001;Walker et al, 2017;Wroblewski et al, 2015). However, traditional genotyping methods are cumbersome, imprecise and investigator/platform dependent, due to the use of capillary electrophoresis to determine the length of STR loci.…”

“…To reliably monitor the spread of SIVcpz in all three Gombe communities, we verified the individual origin of each fecal sample by microsatellite analysis at eight polymorphic STR loci. Thus, most Gombe chimpanzees have been repeatedly genotyped, resulting in a consensus genotype that has been used for paternity and kinship determinations, immunogenetics, microbiome analyses and behavioral studies (Barbian et al, 2018;Keele et al, 2009;Moeller et al, 2016;Rudicell et al, 2010;Santiago et al, 2003;Walker et al, 2017;Wroblewski et al, 2015).…”

The Effects of Temperature on Animal Gut Microbiomes

“…Disruption to the gut microbiota can therefore deleteriously affect host fitness by way of eliminating these beneficial functions. For example, immunocompromised individuals often display an altered gut microbiota (Lozupone et al, 2013;Moeller et al, 2013), which in some cases may contribute to systemic infection and host mortality (Barbian et al, 2018). Although the effects of temperature-induced changes in the gut microbiota on host colonization resistance have not been established, several recent lines of evidence suggest that disruption of animal gut microbiota by temperature may reduce the resistance of hosts to invasion and colonization by microorganisms with pathogenic qualities.…”

Non-Human Primate Models of Enteric Viral Infections

“…Several studies suggested that enteric virome might be in primates found increased [42,43]. This implies that selected enteric virome metrics might be utilized as markers of the disease progression/remission, and also be exploited for evaluation of novel therapies and vaccine approaches.…”