Evaluation of the association between the concentrations of key vaginal bacteria and the increased risk of HIV acquisition in African women from five cohorts: a nested case-control study

McClelland, R. Scott; Lingappa, Jairam R.; Srinivasan, Sujatha; Kinuthia, John; John‐Stewart, Grace; Jaoko, Walter; Richardson, Barbra A.; Yuhas, Krista; Fiedler, Tina L.; Mandaliya, Kishorchandra; Munch, Matthew M; Mugo, Nelly; Cohen, Craig R.; Baeten, Jared M.; Celum, Connie; Overbaugh, Julie; Fredricks, David N.

doi:10.1016/s1473-3099(18)30058-6

Cited by 191 publications

(216 citation statements)

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“…Although compositional analyses using marker gene sequencing have led to important insights into the complexity of the vaginal microbiota as it relates to BV, vaginal inflammation and HIV acquisition , it has several important limitations that need to be considered, such as the inability to provide fine scale taxonomic resolution (species‐ and strain‐level), that these are subject to primer biases, and that they cannot provide exact information about the metabolic functional capacity of bacterial communities.…”

Section: Introductionmentioning

confidence: 99%

The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women

et al. 2019

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Introduction Young women in sub‐Saharan Africa are disproportionately affected by HIV, accounting for 25% of all new infections in 2017. Several behavioural and biological factors are known to impact a young woman's vulnerability for acquiring HIV. One key, but lesser understood, biological factor impacting vulnerability is the vaginal microbiome. This review describes the vaginal microbiome and examines its alterations, its influence on HIV acquisition as well as the efficacy of HIV prevention technologies, the role of the rectal microbiome in HIV acquisition, advances in technologies to study the microbiome and some future research directions. Discussion Although the composition of each woman's vaginal microbiome is unique, a microbiome dominated by Lactobacillus species is generally associated with a “healthy” vagina. Disturbances in the vaginal microbiota, characterized by a shift from a low‐diversity, Lactobacillus ‐dominant state to a high‐diversity non‐ Lactobacillus ‐dominant state, have been shown to be associated with a range of adverse reproductive health outcomes, including increasing the risk of genital inflammation and HIV acquisition. Gardnerella vaginalis and Prevotella bivia have been shown to contribute to both HIV risk and genital inflammation. In addition to impacting HIV risk, the composition of the vaginal microbiome affects the vaginal concentrations of some antiretroviral drugs, particularly those administered intravaginally, and thereby their efficacy as pre‐exposure prophylaxis (PrEP) for HIV prevention. Although the role of rectal microbiota in HIV acquisition in women is less well understood, the composition of this compartment's microbiome, particularly the presence of species of bacteria from the Prevotellaceae family likely contribute to HIV acquisition. Advances in technologies have facilitated the study of the genital microbiome's structure and function. While next‐generation sequencing advanced knowledge of the diversity and complexity of the vaginal microbiome, the emerging field of metaproteomics, which provides important information on vaginal bacterial community structure, diversity and function, is further shedding light on functionality of the vaginal microbiome and its relationship with bacterial vaginosis (BV), as well as antiretroviral PrEP efficacy. Conclusions A better understanding of the composition, structure and function of the microbiome is needed to identify opportunities to alter the vaginal microbiome and prevent BV and reduce the risk of HIV acquisition.

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Section: Introductionmentioning

confidence: 99%

The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women

et al. 2019

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“…A method to infer absolute concentration of multiple bacterial species from NGS data would be extremely useful for the field including studies of the vaginal microbiome. NGS amplicon sequencing is a fractional approach that has been used to help define conditions such as bacterial vaginosis (7–10), and to identify enhanced risk for other sexually transmitted infections and pre-term delivery (11,12). However, total bacterial load may vary significantly between and within individuals over time even over the course of a single day (8).…”

Section: Introductionmentioning

confidence: 99%

Complementing 16S rRNA gene amplicon sequencing with estimates of total bacterial load to infer absolute species concentrations in the vaginal microbiome

Boshier

Srinivasan

Lopez

et al. 2019

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Whereas 16S rRNA gene amplicon sequencing quantifies relative abundances of bacterial taxa, variation in total bacterial load between samples restricts its ability to reflect absolute concentration of individual species. Quantitative PCR (qPCR) can quantify individual species, but it is not practical to develop a suite of qPCR assays for every bacterium present in a diverse sample. We analyzed 1320 samples from 20 women with a history of frequent bacterial vaginosis, who self-collected vaginal swabs daily over 60 days. We inferred bacterial concentrations by taking the product of species relative abundance (assessed by 16S rRNA gene amplicon sequencing) and total bacterial load (measured by broad-range 16S rRNA gene qPCR). Log10-converted inferred concentrations correlated with targeted qPCR (r = 0. 935, p<2.2e-16) for seven key bacterial species. The mean inferred concentration error varied across bacteria, with rarer bacterial vaginosis-associated bacteria associated with larger errors. 92% of errors >0.5 log10 occurred when relative abundance was <10%. Many errors occurred during early bacterial expansion or late contraction. When relative abundance of a species is >10%, inferred concentrations are reliable proxies for targeted qPCR. However, targeted qPCR is required to capture bacteria at low relative abundance, particularly with BV-associated bacteria during the early onset of bacterial vaginosis.

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“…Previous studies have shown that local and systemic inflammation, along with the availability and activation state of target cells, are the major factors in determining the risk for HIV-1 transmission [26]. Studies on vaginal HIV-1 transmission demonstrated that the mucosal microbiome plays an important role in determining HIV-1 susceptibility [65-67]. Previous studies showed that feeding mice a high-fat diet (HFD) resulted in microbial dysbiosis, disruption of the gut epithelial barrier, increased systemic inflammation, and higher numbers of activated immune cells [68, 69].…”

Section: Resultsmentioning

confidence: 99%

Alterations in the gut microbiome by HIV-1 infection or a high-fat diet associates with systemic immune activation and inflammation in double humanized-BLT mice

Daharsh

2020

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9Background 10 While the translatability of gut microbiome studies utilizing animal models to humans has proven 11 difficult, studying the gut microbiome directly in humans is also challenging due to the existence of many 12 confounding variables. Therefore, we utilized double humanized mice, which have both an engrafted 13 stable human-like gut microbiome and functional human immune system. With this model, we were able 14 to determine the in vivo impact of HIV-1 infection or a high-fat diet (HFD) on gut human microbiome 15 composition, and its relationship with human immune cell activation and systemic inflammation. 17 Results 18Surgery was performed on NSG mice to create humanized bone-marrow, liver, thymus mice (hu-mice). In 19 order to create double hu-mice, the hu-mice were treated with broad spectrum antibiotics to deplete 20 murine gut bacteria and subsequently transplanted with human fecal material from healthy human donors. 21We characterized 262 fecal samples from hu-mice, double hu-mice, and human fecal donors to determine 22 the impact of HIV-1 infection or HFD on the gut microbiome and systemic immune activation and 23 inflammation. We found that HIV-1 infection altered the human-like gut microbiome of double hu-mice, 24 which was associated with decreased human CD4 T cells and increased systemic inflammation and 25 2 immune activation. Further, using a HFD we induced gut microbial dysbiosis in double hu-mice which 26 corresponded with increased systemic immune activation and inflammation.

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Evaluation of the association between the concentrations of key vaginal bacteria and the increased risk of HIV acquisition in African women from five cohorts: a nested case-control study

Abstract: National Institute of Child Health and Human Development.

Cited by 191 publications

References 30 publications

The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women

The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women

Complementing 16S rRNA gene amplicon sequencing with estimates of total bacterial load to infer absolute species concentrations in the vaginal microbiome

Alterations in the gut microbiome by HIV-1 infection or a high-fat diet associates with systemic immune activation and inflammation in double humanized-BLT mice

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