.2020 Nov 6;8(1):154.

doi: 10.1186/s40168-020-00928-4.

Shifts in microbial diversity, composition, and functionality in the gut and genital microbiome during a natural SIV infection in vervet monkeys

Anna J Jasinska^{1 2 3}, Tien S Dong⁴, Venu Lagishetty⁴, William Katzka⁴, Jonathan P Jacobs^{4 5 6}, Christopher A Schmitt⁷, Jennifer Danzy Cramer⁸, Dongzhu Ma⁹, Willem G Coetzer¹⁰, J Paul Grobler¹⁰, Trudy R Turner^{10 11}, Nelson Freimer¹², Ivona Pandrea¹³, Cristian Apetrei¹⁴

Affiliations

¹ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA. ankajasinska@gmail.com.
² Department of Molecular Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland. ankajasinska@gmail.com.
³ Eye on Primates, Los Angeles, CA, USA. ankajasinska@gmail.com.
⁴ The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
⁵ Division of Gastroenterology, Hepatology and Parenteral Nutrition, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
⁶ UCLA Microbiome Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
⁷ Department of Anthropology, Boston University, Boston, MA, USA.
⁸ Department of Sociology, Anthropology, and General Studies, American Public University System, Charles Town, WV, USA.
⁹ Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁰ Department of Genetics, University of the Free State, Bloemfontein, South Africa.
¹¹ Department of Anthropology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
¹² Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
¹³ Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁴ Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

PMID:33158452
PMCID: PMC7648414
DOI: 10.1186/s40168-020-00928-4

Shifts in microbial diversity, composition, and functionality in the gut and genital microbiome during a natural SIV infection in vervet monkeys

Anna J Jasinska et al. Microbiome.2020.

.2020 Nov 6;8(1):154.

doi: 10.1186/s40168-020-00928-4.

Authors

Affiliations

¹ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA. ankajasinska@gmail.com.
² Department of Molecular Genetics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland. ankajasinska@gmail.com.
³ Eye on Primates, Los Angeles, CA, USA. ankajasinska@gmail.com.
⁴ The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
⁵ Division of Gastroenterology, Hepatology and Parenteral Nutrition, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA.
⁶ UCLA Microbiome Center, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
⁷ Department of Anthropology, Boston University, Boston, MA, USA.
⁸ Department of Sociology, Anthropology, and General Studies, American Public University System, Charles Town, WV, USA.
⁹ Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁰ Department of Genetics, University of the Free State, Bloemfontein, South Africa.
¹¹ Department of Anthropology, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
¹² Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA.
¹³ Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
¹⁴ Division of Infectious Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

PMID:33158452
PMCID: PMC7648414
DOI: 10.1186/s40168-020-00928-4

Abstract

Background: The microbiota plays an important role in HIV pathogenesis in humans. Microbiota can impact health through several pathways such as increasing inflammation in the gut, metabolites of bacterial origin, and microbial translocation from the gut to the periphery which contributes to systemic chronic inflammation and immune activation and the development of AIDS. Unlike HIV-infected humans, SIV-infected vervet monkeys do not experience gut dysfunction, microbial translocation, and chronic immune activation and do not progress to immunodeficiency. Here, we provide the first reported characterization of the microbial ecosystems of the gut and genital tract in a natural nonprogressing host of SIV, wild vervet monkeys from South Africa.

Results: We characterized fecal, rectal, vaginal, and penile microbiomes in vervets from populations heavily infected with SIV from diverse locations across South Africa. Geographic site, age, and sex affected the vervet microbiome across different body sites. Fecal and vaginal microbiome showed marked stratification with three enterotypes in fecal samples and two vagitypes, which were predicted functionally distinct within each body site. External bioclimatic factors, biome type, and environmental temperature influenced microbiomes locally associated with vaginal and rectal mucosa. Several fecal microbial taxa were linked to plasma levels of immune molecules, for example, MIG was positively correlated with Lactobacillus and Escherichia/Shigella and Helicobacter, and IL-10 was negatively associated with Erysipelotrichaceae, Anaerostipes, Prevotella, and Anaerovibrio, and positively correlated with Bacteroidetes and Succinivibrio. During the chronic phase of infection, we observed a significant increase in gut microbial diversity, alterations in community composition (including a decrease in Proteobacteria/Succinivibrio in the gut) and functionality (including a decrease in genes involved in bacterial invasion of epithelial cells in the gut), and partial reversibility of acute infection-related shifts in microbial abundance observed in the fecal microbiome. As part of our study, we also developed an accurate predictor of SIV infection using fecal samples.

Conclusions: The vervets infected with SIV and humans infected with HIV differ in microbial responses to infection. These responses to SIV infection may aid in preventing microbial translocation and subsequent disease progression in vervets, and may represent host microbiome adaptations to the virus. Video Abstract.

Keywords: Acute infection; Microbiome; Primate; Proteobacteria; SIV; Succinivibrio.

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Conflict of interest statement

Not applicable.

Figures

**Fig. 1**
Characterization of the natural gut and genital microbiota in vervet monkeys.a PCoA,b alpha diversity, and taxonomic summaries at thec phylum andd genus levels across four body sites (fecalN = 44, rectalN = 103, penileN = 20 and vaginalN = 51). Firmicutes and Bacteroidetes are the most abundant bacteria in all sample types. Fusobacteria and Actinobacteria are common in the genital microbiome, and Spirochaetes and Proteobacteria are common in the gut microbiome. *Comparison versus fecal samples. +Comparison versus rectal samples. #Comparison versus vaginal samples. *+#p value ≤ 0.05

**Fig. 2**
Bacteriological ecosystems in the gut and vaginal microbiomes in vervet monkeys.a Three enterotypes in fecal microbiome (N = 44) indicated by PCoA clustering andb their genus level taxonomic summaries.c Microbial profiles of the vaginal microbiome (N = 51) of individual vervet monkeys.d PCoA visualization of microbial compositional differences between the two vagitypes.e Differentially abundant microbial functional pathways between the two vagitypes (only top 30 abundant pathways represented)

**Fig. 3**
SIV infection is associated with higher microbial diversity and altered microbiome composition and function. Characterization of SIVpos and SIVneg samples (respectively, 62 and 41 from the rectum, 33 and 11 from the feces, 11 and 9 from the penis, and 41 and 10 from the vagina) with respect toa alpha diversity in feces, stratified by SIV status andb community structure for four body sites stratified by SIV positive/negative status.c Differentially abundant genera between SIVpos and SIVneg individuals at all body sites (There were no differentially abundant genera in penile samples). Analysis was adjusted for age, sex, and vervet location.d Functional pathways associated with SIV infection in the predicted metagenome of fecal samples

**Fig. 4**
Microbiome across stages of SIV infection in vervets.a PCoA colored by stages of SIV infection.P values are adjusted for collection site, gender, and age.b Alpha diversity as presented by Shannon index across different body sites and SIV stages.c Distance box plots comparing distances within a particular SIV stage (i.e., all within) and between SIV infection states across different sample types. The first boxplot contains the distances between all samples that are within the same category, i.e., within negative samples, within acutely infected samples and within chronically infected (all within). The subsequent boxplots represent the distances between all samples in different categories: all chronic samples vs all negative samples, all chronic samples vs. all acute samples, and all negative samples vs. all acute samples. The microbiome samples comprise of the fecal samples (11 SIV negative, 4 acutely infected, 23 chronically infected), rectal samples (41 SIV negative, 11 acutely infected, 43 chronically infected), vaginal samples (10 SIV negative, 6 acutely infected, 30 chronically infected), and penile samples (9 SIV negative, 2 acutely infected, 8 chronically infected). *Indicates comparisons with ap value < 0.05

**Fig. 5**
SIV infection classifier based on the fecal microbiota (N =44).a ROC curve with AUROC of 0.95, sensitivity 0.5, and specificity 0.97 andb most important taxa for the predictor. Variables with higher mean decrease accuracy have a greater contribution to the accuracy of the classifier

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Shifts in microbial diversity, composition, and functionality in the gut and genital microbiome during a natural SIV infection in vervet monkeys

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Shifts in microbial diversity, composition, and functionality in the gut and genital microbiome during a natural SIV infection in vervet monkeys

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