Picker, M. | Search bioRxiv

bioRxiv2025

Maternal IBD-related antibodies are associated with early life gut inflammatory status and microbiota composition: insights from cord blood

PurposeAntibodies in peripheral blood are used to aid in the diagnosis of inflammatory bowel disease (IBD), but their presence in neonatal cord blood and potential effects on early life development remain unknown. MethodsWe measured anti-CBir1, ANCA, anti-OmpC, ASCA IgA, and ASCA IgG levels in the cord blood of babies born to 78 mothers with or without IBD. Their association with fecal calprotectin (FC), and microbiota composition, characterized by 16S rRNA sequencing, was assessed throughout pregnancy and during the first 3 years of life using linear mixed-effects models. ResultsAntibodies were detected in cord blood, with significantly higher levels of anti-CBir1 and ASCA IgG in babies born to mothers with Crohns disease (p = 0.002) and higher abundance of ANCA and anti-OmpC in babies of mothers with ulcerative colitis (p = 0.002), compared to controls. ASCA IgG levels positively correlated with babies FC (p = 0.006), while babies microbiota Shannon diversity was negatively associated with ANCA, anti-OmpC, and ASCA IgA levels (p = 0.003, 0.04, and 0.008, respectively). Romboutsia spp., Citrobacter spp., Pseudomonas spp., Clostridiaceae, Clostridia, and Varibaculum spp. were positively correlated with either or both ANCA and anti-OmpC levels (all multiple testing adjusted q < 0.1). ConclusionOur findings suggest that maternal IBD-associated antibodies cross the placenta barrier and may be associated with intestinal inflammation and imbalanced microbiota colonization. Whether these serological profiles negatively influence the priming of the babys immune system or IBD risk later in life remains to be determined.

immunology↗

bioRxiv2024

Association of diet and inflammation with the vaginal microbiota of pregnant individuals with or without IBD

Background and aimsVaginal dysbiosis has been associated with adverse pregnancy outcomes. Here, we characterized the vaginal microbiota of pregnant individuals with inflammatory bowel disease (IBD) and investigated whether gut or vaginal inflammation and diet influence the vaginal microbiota diversity of these individuals. Study DesignWe recruited 48 individuals in their third trimester of pregnancy (IBD=23 and HC=18). We characterized the vaginal microbiota by 16S rRNA sequencing and the gut microbiota by shotgun sequencing. We measured fecal calprotectin in stool and pro-inflammatory cytokines in vaginal fluids. We determine dietary quality using validated 24-hour dietary recalls. ResultsPregnant individuals with IBD exhibit higher levels of fecal calprotectin and increased expression of Th17 pro-inflammatory cytokines (i.e., IL-6, IL-8, IL-17) in the vaginal mucosa compared to healthy pregnant individuals. High fecal calprotectin correlated with high vaginal microbiota diversity. Also, IL-4 (reduced in IBD) was associated with vaginal microbial composition. Regardless of IBD status, pregnant individuals with healthier diets and particularly optimal servings of vegetables and sugars exhibited a vaginal microbiota dominated by Lactobacillus crispatus, a species associated with a lower risk of preterm birth and bacterial vaginosis. ConclusionBesides gut inflammation, pregnant individuals with IBD also exhibit a Th17 immune tone in the vaginal mucosa. The vaginal microbiota diversity or composition, particularly high in the beneficial L. crispatus, is positively associated with healthier diets, regardless of IBD status. Why was the study conducted?An altered vaginal microbiota has been implicated in preterm birth. There is no research on the vaginal microbiome and the factors that influence it in pregnant individuals with Inflammatory Bowel Disease (IBD) at a higher risk of preterm delivery. Key findingsPregnant individuals with IBD exhibit a comparable vaginal microbiome to healthy pregnant individuals. However, pregnant individuals with IBD present a vaginal immune profile characterized by increased levels of Th17 pro-inflammatory cytokines. High dietary quality, and optimal consumption of vegetables and added sugars were associated with vaginal dominance by the beneficial L. crispatus. What does this add to what is known?Our results indicate that the vaginal immune environment and not the microbiome might explain poor pregnancy outcomes for individuals with IBD. Moreover, our study supports the importance of diet to favor L. crispatus, a bacterium associated with a lower risk of preterm birth.

microbiology↗