The Vaginal Microbiota over an 8- to 10-Year Period in a Cohort of HIV-Infected and HIV-Uninfected Women

Mehta, Supriya D.; Donovan, Brock; Weber, Kathleen M.; Cohen, Mardge H.; Ravel, Jacques; Gajer, Pawel; Gilbert, Douglas; Burgad, Derick; Spear, Greg T.

doi:10.1371/journal.pone.0116894

Cited by 35 publications

(28 citation statements)

References 55 publications

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“…Analysis of the vaginal microbiome showed notable associations between high diversity states, high pH, and BV as inferred from Nugent scores, paralleling previous studies [9, 11, 18, 39] . Previous studies have differed on associations between HIV status and BV [26–28, 30, 31] —here we found that HIV+ status was correlated with BV status.…”

Section: Discussioncontrasting

confidence: 45%

“…DNA was purified from cervical or cervicovaginal mucus, then samples amplified with 16S rRNA gene primers targeting the V1V2 region [34–37] . This primer set has been used in previous studies of the vaginal microbiome [30] , and is generally effective at recovering 16S sequences from vaginal organisms. Sequence data was acquired using the Illumina MiSeq platform (paired end sequencing, average of 50,127 sequences per sample).…”

Section: Resultsmentioning

confidence: 99%

“…BV is known to be more common in African American women, motivating studies of associations with HIV infection [29] . In contrast, a study of the vaginal microbiome in 64 women in Chicago showed no differences associated with HIV infection [30] . Another study, comparing vaginal microbiota in women from Rwanda and the US together with HIV status, found modest differences for both geographic site and infection status [31] .…”

Section: Introductionmentioning

confidence: 99%

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Associations of the vaginal microbiota with HIV infection, bacterial vaginosis, and demographic factors

Chehoud

Stieh

Bailey

et al. 2017

Aids

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Objective We sought to investigate the effects of HIV infection on the vaginal microbiota, and associations with treatment and demographic factors. We thus compared vaginal microbiome samples from HIV+ and HIV− women collected at two Chicago area hospitals. Design We studied vaginal microbiome samples from 178 women analyzed longitudinally (n=324 samples), and collected extensive data on clinical status and demographic factors. Methods We used 16S rRNA gene sequencing to characterize the bacterial lineages present, then UniFrac, Shannon Diversity and other measures to compare community structure to sample metadata. Results Differences in microbiota measures were modest in the comparison of HIV+ and HIV− samples, in contrast to several previous studies, consistent with effective antiretroviral therapy. Proportions of healthy Lactobacillus species were not higher in HIV-negative subjects overall, but were significantly higher when analyzed within each hospital in isolation. Rates of bacterial vaginosis (BV) were higher among African American women and HIV+ women. BV was associated with higher frequency of HIV+. Unexpectedly, African-American women were more likely to switch BV status between sampling times; switching was not associated with HIV+ status. Conclusions The influence of HIV infection on the vaginal microbiome was modest for this cohort of well-suppressed urban American women, consistent with effective anti-retroviral therapy. HIV+ was found to be associated with BV. Although BV has previously been associated with HIV transmission, most of the women studied here became HIV+ many years before our test for BV, thus implicating additional mechanisms linking HIV infection and BV.

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Section: Discussioncontrasting

confidence: 45%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Associations of the vaginal microbiota with HIV infection, bacterial vaginosis, and demographic factors

Chehoud

Stieh

Bailey

et al. 2017

Aids

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“…vaginalis may actually consist of several species with distinct roles in BV pathogenesis has only recently been investigated [5, 7, 8]. Studies based on 16S rRNA variable-region targeted sequencing have known biases against detecting Gardnerella at all [24, 25], much less resolving subgroups, although one early deep sequencing study did distinguish four G . vaginalis subgroups based on a single nucleotide difference in variable region 6 of the 16S rRNA gene [26].…”

Section: Discussionmentioning

confidence: 99%

Gardnerella vaginalis Subgroups Defined by cpn60 Sequencing and Sialidase Activity in Isolates from Canada, Belgium and Kenya

et al. 2016

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Increased abundance of Gardnerella vaginalis and sialidase activity in vaginal fluid is associated with bacterial vaginosis (BV), a common but poorly understood clinical entity associated with poor reproductive health outcomes. Since most women are colonized with G. vaginalis, its status as a normal member of the vaginal microbiota or pathogen causing BV remains controversial, and numerous classification schemes have been described. Since 2005, sequencing of the chaperonin-60 universal target (cpn60 UT) has distinguished four subgroups in isolate collections, clone libraries and deep sequencing datasets. To clarify potential clinical and diagnostic significance of cpn60 subgroups, we undertook phenotypic and molecular characterization of 112 G. vaginalis isolates from three continents. A total of 36 subgroup A, 33 B, 35 C and 8 D isolates were identified through phylogenetic analysis of cpn60 sequences as corresponding to four “clades” identified in a recently published study, based on sequencing 473 genes across 17 isolates. cpn60 subgroups were compared with other previously described molecular methods for classification of Gardnerella subgroups, including amplified ribosomal DNA restriction analysis (ARDRA) and real-time PCR assays designed to quantify subgroups in vaginal samples. Although two ARDRA patterns were observed in isolates, each was observed in three cpn60 subgroups (A/B/D and B/C/D). Real-time PCR assays corroborated cpn60 subgroups overall, but 13 isolates from subgroups A, B and D were negative in all assays. A putative sialidase gene was detected in all subgroup B, C and D isolates, but only in a single subgroup A isolate. In contrast, sialidase activity was observed in all subgroup B isolates, 3 (9%) subgroup C isolates and no subgroup A or D isolates. These observations suggest distinct roles for G. vaginalis subgroups in BV pathogenesis. We conclude that cpn60 UT sequencing is a robust approach for defining G. vaginalis subgroups within the vaginal microbiome.

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“…To identify whether any singular OTUs correlated with changes in pH, we applied a generalized linear mixed model approach that takes into account subject-specificity. 37-39 Within duodenal samples (n=56), we observed 15 OTUs that significantly correlated with pH changes. Linear regression of pH and relative abundance of these OTUs was significant across all samples (Figure 5; Table S2).…”

Section: Resultsmentioning

confidence: 88%

Spatial and Temporal Analysis of the Stomach and Small Intestinal Microbiota in Fasted Healthy Humans

Seekatz

Schnizlein

Koenigsknecht

et al. 2018

Preprint

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Although the microbiota in the proximal gastrointestinal (GI) tract has been implicated in health and disease, much of these microbes remains understudied compared to the distal GI tract. This study characterized the microbiota across multiple proximal GI sites over time in healthy individuals.As part of a study of the pharmacokinetics of oral mesalamine administration, healthy, fasted volunteers (N=8; 10 observation periods total) were orally intubated with a four-lumen catheter with multiple aspiration ports. Samples were taken from stomach, duodenal, and multiple jejunal sites, sampling hourly (≤7 hours) to measure mesalamine (administered at t=0), pH, and 16S rRNA gene-based composition.We observed a predominance of Firmicutes across proximal GI sites, with significant variation compared to stool. The microbiota was more similar within individuals over time than between subjects, with the fecal microbiota being unique from that of the small intestine. The stomach and duodenal microbiota displayed highest intra-individual variability compared to jejunal sites, which were more stable across time. We observed significant correlations in the duodenal microbial composition with changes in pH; linear mixed models identified positive correlations with multiple Streptococcus operational taxonomic units (OTU) and negative correlations with multiple Prevotella and Pasteurellaceae OTUs. Few OTUs correlated with mesalamine concentration.The stomach and duodenal microbiota exhibited greater compositional dynamics compared to the jejunum. Short-term fluctuations in the duodenal microbiota was correlated with pH. Given the unique characteristics and dynamics of the proximal GI tract microbiota, it is important to consider these local environments in health and disease states.

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The Vaginal Microbiota over an 8- to 10-Year Period in a Cohort of HIV-Infected and HIV-Uninfected Women

Cited by 35 publications

References 55 publications

Associations of the vaginal microbiota with HIV infection, bacterial vaginosis, and demographic factors

Associations of the vaginal microbiota with HIV infection, bacterial vaginosis, and demographic factors

Gardnerella vaginalis Subgroups Defined by cpn60 Sequencing and Sialidase Activity in Isolates from Canada, Belgium and Kenya

Spatial and Temporal Analysis of the Stomach and Small Intestinal Microbiota in Fasted Healthy Humans

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