A longitudinal analysis of the vaginal microbiota and vaginal immune mediators in women from sub-Saharan Africa

Abstract

In cross-sectional studies increased vaginal bacterial diversity has been associated with vaginal inflammation which can be detrimental for health. We describe longitudinal changes at 5 visits over 8 weeks in vaginal microbiota and immune mediators in African women. Women (N = 40) with a normal Nugent score at all visits had a stable lactobacilli dominated microbiota with prevailing Lactobacillus iners. Presence of prostate-specific antigen (proxy for recent sex) and being amenorrhoeic (due to progestin-injectable use), but not recent vaginal cleansing, were significantly associated with microbiota diversity and inflammation (controlled for menstrual cycle and other confounders). Women (N = 40) with incident bacterial vaginosis (Nugent 7–10) had significantly lower concentrations of lactobacilli and higher concentrations of Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia, at the incident visit and when concentrations of proinflammatory cytokines (IL-1β, IL-12p70) were increased and IP-10 and elafin were decreased. A higher ‘composite-qPCR vaginal-health-score’ was directly associated with decreased concentrations of proinflammatory cytokines (IL-1α, IL-8, IL-12(p70)) and increased IP-10. This longitudinal study confirms the inflammatory nature of vaginal dysbiosis and its association with recent vaginal sex and progestin-injectable use. A potential role for proinflammatory mediators and IP-10 in combination with the vaginal-health-score as predictive biomarkers for vaginal dysbiosis merits further investigation.

Medroxyprogesterone acetate mediated alteration in the vaginal microbiota and microenvironment in a Kenyan sex worker cohort

“…A study by Birse et al, 2017 found no significant association between DMPA and bacterial diversity (Shannon Diversity Index) in non-sex workers, however women with BV were not excluded (43). The results of the present study support those of Jespers et al, 2017 who demonstrated that injectable progestins (including DMPA) were associated with VMB diversity and reduced concentration of lactobacilli in African women (10). Although another study included non-sex workers of varying ethnicities, and included BV, bacterial diversity (by inverse Simpson’s index) was significantly lower in women on OCPs than DMPA or not on hormonal contraceptives, and although not statistically significant, women on DMPA had greater bacterial diversity than women not on hormonal contraceptives (8).…”

“…However two independent prospective studies have shown the Shannon Diversity Index remains stable across the menstrual cycle (19, 48). We thus believe results represent an accurate depiction of the effect of MPA on VMB diversity and the vaginal microenvironment in sex workers, especially given results of recent studies (8, 10).…”

“…Although we and others (10) demonstrate that DMPA is associated with enhanced diversity of the VMB by 16S rRNA gene sequencing in women with Nugent scores <7, it is important to note that hormonal contraceptives (DMPA and OCPs) are typically associated with a reduced incidence and prevalence of BV, as assessed by Nugent scoring (39). The implication is that DMPA and OCPs therefore reduce “bacterial diversity” but the bacterial diversity assessed by Nugent scoring is based on microscopic visualization of bacterial morphotypes and may not be as sensitive in assessing bacterial diversity as the α-diversity metrics that can be calculated by 16S rRNA gene sequencing.…”

“…Several studies report the effect of hormonal contraceptives on the VMB (2, 5-10, 42-44). While some studies found subtle VMB shifts in women on hormonal contraceptives like enhanced Lactobacillus species (5, 8), reduced total bacteria (9), G. vaginalis (9), or lactobacilli (6), the majority do not show any major effects of hormonal contraceptives on VMB clustering (2, 7, 43) or associations between hormonal contraceptives and the proportion Lactobacillus -dominant VMB (42).…”

“…Studies have suggested several biological mechanisms, including hypo-estrogenism, by which DMPA might enhance susceptibility to HIV-1 and other sexually transmitted infections (STIs) (4). However, few (5-10) examine the relationship between hormonal contraceptives and the vaginal microbiota (VMB), even though diverse VMB, low in Lactobacillus species, confers a 4-fold increased risk of HIV-1 (11). Herein, we determined the effect of MPA (active component of DMPA) on several factors within the vaginal microenvironment of Kenyan sex workers, including diversity of the VMB.…”