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. 2022 May 20;12(1):8573.
doi: 10.1038/s41598-022-12424-w.

HIV-associated vaginal microbiome and inflammation predict spontaneous preterm birth in Zambia

Joan T Price  1   2   3 , Bellington Vwalika  4 , Michael France  5 , Jacques Ravel  5 , Bing Ma  5 , Humphrey Mwape  6 , Katelyn J Rittenhouse  7 , Kristina De Paris  8 , Marcia Hobbs  8 , Julie A Nelson  8 , Margaret P Kasaro  4   6 , Elizabeth M Stringer  7 , Jeffrey S A Stringer  7
Affiliations

HIV-associated vaginal microbiome and inflammation predict spontaneous preterm birth in Zambia

Joan T Price et al. Sci Rep. .

Abstract

A Lactobacillus-deficient, anaerobe-rich vaginal microbiome has been associated with local inflammation and spontaneous preterm birth (sPTB), but few studies have assessed this association in the setting of HIV. We performed metagenomic sequencing and inflammatory marker assays on vaginal swabs collected in pregnancy. We grouped samples into 7 metagenomic clusters (mgClust) using the non-redundant VIRGO catalogue, and derived inflammatory scores by factor analysis. Of 221 participants, median Shannon diversity index (SDI) was highest in HIV+ with detectable viral load (1.31, IQR: 0.85-1.66; p < 0.001) and HIV+ with undetectable virus (1.17, IQR: 0.51-1.66; p = 0.01) compared to HIV- (0.74, IQR: 0.35-1.26). Inflammatory scores positively correlated with SDI (+ 0.66, 95%CI 0.28, 1.03; p = 0.001), highest among anaerobe-rich mgClust2-mgClust6. HIV was associated with predominance of anaerobe-rich mgClust5 (17% vs. 6%; p = 0.02) and mgClust6 (27% vs. 11%; p = 0.002). Relative abundance of a novel Gardnerella metagenomic subspecies > 50% predicted sPTB (RR 2.6; 95%CI: 1.1, 6.4) and was higher in HIV+ (23% vs. 10%; p = 0.001). A novel Gardnerella metagenomic subspecies more abundant in women with HIV predicted sPTB. The risk of sPTB among women with HIV may be mediated by the vaginal microbiome and inflammation, suggesting potential targets for prevention.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Flowchart of ZAPPS participants with term or spontaneous preterm birth (sPTB) included in vaginal microbiome and cytokine analyses at baseline (16–20 gestational weeks) and repeat (24–36 gestational weeks) timepoints.
Figure 2
Figure 2
Proportions of assignable Gardnerella abundance in two distinct profiles of metagenomic subspecies of Gardnerella present in vaginal specimens collected between 16–20 weeks and 24–36 weeks, N = 152.
Figure 3
Figure 3
Heat map of vaginal microbial composition of all specimens collected between 16–20 weeks 24–36 weeks, N = 287.
Figure 4
Figure 4
Prevalence of metagenomic community cluster (mgClust) by HIV status and viral load (VL) at 16–20 gestational weeks. Relative percents weighted for sampling and p values calculated by weighted logistic regression with HIV− as comparator group.
Figure 5
Figure 5
Median Shannon diversity indices (SD) and inflammatory scores (IS) by metagenomic clusters (mgClust) in vaginal specimens collected between 16–20 gestational weeks. p values calculated by weighted linear regression of SD and IS in each mgClust compared to L. crispatus-dominant mgClust 7, adjusting for HIV serostatus at enrollment.
Figure 6
Figure 6
Prevalence of metagenomic clusters (mgClust) at 16–20 gestational weeks among participants with term birth, spontaneous preterm birth at 34–36 weeks (sPTB 34–36), and spontaneous preterm birth before 34 weeks (sPTB < 34). Relative percents weighted for sampling and p values calculated by weighted Poisson regression of prevalence of mgClust between preterm birth outcomes compared to term; * p < 0.05; ** p < 0.001.
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