Association Between Maternal IBD-Related Antibodies and Early Life Gut Inflammatory Status and Microbiota Composition: Insights from Cord Blood

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Purpose: Antibodies 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. Methods: We 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 three and five years of life, respectively, using linear mixed-effects models. Results: Antibodies were detected in cord blood, with significantly higher levels of anti-CBir1 and ASCA IgG in babies born to mothers with Crohn’s 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). Both ANCA and anti-OmpC were positively correlated with the abundance of Romboutsia spp. Clostridia , and Pseudomonas spp. while Blautia spp. Citrobacter spp. Clostridiaceae , and Varibaculum spp. were positively correlated with either ANCA or anti-OmpC levels. Higher abundance of Lactobacillus spp. was associated with higher ASCA IgG and anti-CBir1 levels (all multiple testing-adjusted q< 0.1). Conclusion: Our 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 baby’s immune system or IBD risk later in life remains to be determined. Keywords: anti-CBir1, ANCA, anti-OmpC, ASCA, inflammatory bowel disease, pregnancy

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