Association of vaginal IL-4, IL-6, IL-8, IL-17, IFN-γ, and dietary intake with IBD status and vaginal microbiota in pregnant individuals

Abstract

Background Pregnant individuals with inflammatory bowel diseases (IBD) exhibit gut inflammation and dysbiosis; however, there is limited knowledge about their vaginal environment. This is important as vaginal inflammation and high vaginal microbiota diversity are associated with adverse pregnancy outcomes. Objectives We aimed to compare vaginal inflammatory markers and microbiota diversity of pregnant individuals with and without IBD in their third trimester of pregnancy and determine the role of diet in the vaginal microbiota diversity. Methods We recruited pregnant individuals who provided vaginal swabs at 27–29 weeks of pregnancy. We characterized the vaginal microbiota by sequencing the V3-V4 region of the 16S rRNA and surveyed nine key pro and anti-inflammatory cytokines by qRT-PCR from the vaginal mucosa. Participants completed three validated interviewer-led nutrition assessments of 24-hour dietary intake around the same time as the collection of vaginal samples. The nutritional assessments were used to estimate dietary quality using the validated Healthy Eating Index (HEI-2015). Results The cohort included 23 pregnant individuals with IBD (18 with Crohn’s disease and 5 with ulcerative colitis) and 25 healthy controls (HC); 56.5% of the IBD cases were in remission. Vaginal microbiota diversity and composition did not differ significantly between individuals with IBD and HC. However, the vaginal mucosa of the IBD individuals showed increased expression of Th17 pro-inflammatory cytokines (i.e., IL-6, IL-8, IL-17) and decreased expression of Th1 (IFN-γ) and Th2 (IL-4) compared to HC. Expression of IL-6 and TNF- α correlated positively with vaginal microbial diversity. The beneficial Lactobacillus crispatus dominated the vaginal microbiota of individuals with either high dietary quality or those consuming more vegetables or low added sugar, regardless of IBD status . In IBD cases, consumption of vegetables and added sugars were associated with reduced expression of the pro-inflammatory IFN-γ and an increased expression of anti-inflammatory IL-4. Conclusion The vaginal microbiome did not differ between individuals with IBD and HC; however, IBD cases exhibit a pro-inflammatory tone in the vagina (high IL-6) that is associated with higher vaginal microbial diversity. Regardless of IBD status, healthier diets are positively associated with an increased abundance of the beneficial L. crispatus in the vagina.