The association between obesity and weight loss after bariatric surgery on the vaginal microbiota

Abstract

Background: Obesity and vaginal microbiome (VMB) dysbiosis are each risk factors for adverse reproductive and oncological health outcomes in women. Here, we investigated the relationship between obesity, vaginal bacterial composition, local inflammation and bariatric surgery.

Methods: Vaginal bacterial composition assessed by high-throughput sequencing of bacterial 16S rRNA genes and local cytokine levels measured using a multiplexed Magnetic Luminex Screening Assay were compared between 67 obese and 42 non-obese women. We further assessed temporal changes in the microbiota and cytokines in a subset of 27 women who underwent bariatric surgery.

Results: The bacterial component of the vaginal microbiota in obese women was characterised by a lower prevalence of a Lactobacillus-dominant VMB and higher prevalence of a high diversity (Lactobacillus spp., and Gardnerella- spp. depleted) VMB, compared with non-obese subjects (p<0.001). Obese women had higher relative abundance of Dialister species (p<0.001), Anaerococcus vaginalis (p=0.021), and Prevotella timonensis (p=0.020) and decreased relative abundance of Lactobacillus crispatus (p=0.014). Local vaginal IL-1β, IL-4, IL-6, IL-8, IFNγ, MIP-1α and TNFα levels were all higher among obese women, however, only IL-1β and IL-8 correlated with VMB species diversity. In a subset of obese women undergoing bariatric surgery, there were no significant overall differences in VMB following surgery; however, 75% of these women remained obese at 6 months. Prior to surgery, there was no relationship between body mass index (BMI) and VMB structure; however, post-surgery women with a Lactobacillus-dominant VMB had a significantly lower BMI than those with a high diversity VMB.

Conclusions: Obese women have a significantly different vaginal microbiota composition with increased levels of local inflammation compared to non-obese women. Bariatric surgery does not change the VMB; however, those with the greatest weight loss 6-month post-surgery are most likely to have a Lactobacillus-dominant VMB. Video abstract.

Keywords: BMI; Bariatric surgery; Body mass index; Obesity; Overweight; Vaginal microbiota.

Fig. 1

a Hierarchical clustering analysis of genera taxonomic level data generates three distinct groups consisting of (i) Lactobacillus-dominant (characterised by high relative abundance of Lactobacillus spp.), (ii) Gardnerella-dominant (characterised by high relative abundance of Gardnerella spp. and low relative abundance of Lactobacillus spp.) and (iii) high diversity vaginal microbiome (VMB)—characterised by low relative abundance of each of Lactobacillus and Gardnerella species, and increased bacterial diversity. Heatmap created from all samples collected (n=166), using Ward linkage with the fifty most commonly identified microbial genera shown. Cohort characteristics including BMI category, menopause status, ethnicity, contraceptive or hormone replacement therapy (HRT) use and diabetic status are also shown below the heatmap

Fig. 2

a The prevalence of the Lactobacillus-dominant genus group was lower in obese compared to non-obese women (p<0.001). b Number of species observed (Sobs) increased with obesity (p=0.002). c Significantly increased microbial diversity was seen among obese women (p=0006). d The vaginal microbiome of obese women was characterised at genus level by increased mean proportion (%) of Dialister, Prevotella and Anaerococcus. Results at species level showed increased mean proportion (%) of Dialister (unclassified), Prevotella timonensis and Anaerococcus vaginalis in obese women, and Lactobacillus crispatus dominated among non-obese women

Fig. 3

Pro-inflammatory local vaginal cytokine expression is increased in obesity. a Expression levels (log₁₀) of seven cytokines measured among non-obese and obese women in the baseline cohort. Pro-inflammatory cytokines IL-1β, IL-8, IFNγ and MIP-1α all showed significantly increased expression among obese women (p<0.001). Anti-inflammatory cytokine IL-4 also had increased significance in obese women (p<0.001). b Expression of seven local cervicovaginal cytokine levels (log₁₀) according to obesity status and species diversity (non-parametric Shannon indices). As the diversity of vaginal bacterial species increases, there is a significant increase in expression of pro-inflammatory cytokines IL-1β and IL-8, dependent on obesity status

Fig. 4

a Differences in proportion of vaginal microbiota groups from baseline (day of surgery) to 6 months post-surgery in the bariatric cohort. b The mean BMI of each of the three genus groups at baseline sampling and at 6 months post-surgery. There was a significant reduction in mean BMI in Lactobacillus-dominant VMB samples at 6 months post bariatric surgery (p<0.001). c The mean BMI of each of the three genus groups at baseline and 6 months post-surgery, according to menopause status. There was a significant reduction in mean BMI in the Lactobacillus-dominant group in premenopausal (p=0.002) and postmenopausal women (p=0.009)