Influence of early life factors on the development of intestinal microbiota of infants born to mothers with and without IBD

Abstract Background Inflammatory bowel diseases (IBD) are associated with a dysregulation of the intestinal microbiota and some of these dysbiotic taxa may be transmitted to the offspring of pregnant patients with IBD. We analysed the influence of early life events on the development of the intestinal microbiota of infants born to mothers with and without IBD. Methods The MECONIUM (Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome) study is a prospective cohort study including pregnant women with or without IBD and their infants. Stool samples were collected during pregnancy and in babies throughout the first 2 years of life. Stool microbiota composition in the baby stool was assessed using 16S rRNA sequencing. Results We analysed 1037 faecal samples from 294 infants (born to 80 mothers with and 214 without IBD). The overall composition of the microbiota at 1 month was influenced by the mode of delivery (r = 0.1224, p = 0.001), feeding (breastfeeding, formula feeding or mixed; r = 0.0366, p = 0.013), and antibiotics (r = 0.0446, p = 0.004), and this was mainly driven by α-diversity (Simpson, r = 0.0529, p = 0.012), and the relative abundance of Bacteroides (r = 0.8738, p = 0.001), Bifidobacterium (r = 0.4282, p = 0.001), and Klebsiella (r = 0.6182, p = 0.001). Univariate and multivariate analysis confirmed the influence of mode of delivery in the relative abundance of Bacteroides (increased in vaginal delivery, Wilcoxon FDR p = 2.50e−07, Maaslin FDR p = 0.0016) at month 1. At month 3, mode of delivery (r = 0.0779, p = 0.001), IBD status of the mothers (r = 0.0253, p = 0.028), and pre-term birth (r = 0.0208, p = 0.045) influenced the overall composition of the microbiota, with the main drivers being Bifidobacterium (r = 0.8844, p = 0.001), Bacteroides (r = 0.8632, p = 0.001), and Klebsiella (r = 0.4374, p = 0.001). Univariate and multivariate analysis confirmed the influence of mode of delivery in the relative abundance of Bacteroides (increased in vaginal delivery, Wilcoxon FDR p = 1.23e−06, Maaslin FDR p = 0.07). None of the evaluated variables could significantly explain the variation of the overall composition of the microbiota at 1 year of life. IBD status of the mother influences the microbiota composition of 2-year-old infants; however, this association was only significant in vector fitting analysis. Conclusion Maternal IBD status is shaping early life microbiota in their offspring, likely due to altered microbiota in mothers with IBD. Additionally, the mode of delivery, feeding, and exposure to antibiotics are important determinants of the infant′s microbiota. These influences are lost with time, probably due to increasing exposure to several sources of microbiota and to confounding factors (e.g. diet).