Background: Human studies have demonstrated changes in the diversity and abundance of the microbiome during pregnancy coinciding with changes in maternal immune status. Furthermore, accumulating evidence suggests that maternal health may influence the newborn's microbiome development. These balancing acts may be even more complicated in pregnant women with IBD, who exhibit a variety of immunological and gut microbiota alterations. Yet, no data exist on the effect of IBD on the microbiome during pregnancy, and its role on the infant gut microbiota composition.
Methods: The “Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome” (MECONIUM) Study is a prospective study that recruits pregnant women with and without IBD and their offspring. Stool and saliva samples were collected during pregnancy, and placenta was collected at delivery. Serial stool samples were collected from the newborns up to 90 days of life. The microbial composition was surveyed using 16S rRNA sequencing. QIIME was used to compare the overall microbiota diversity, and the LEfSe method was used to find differential taxa features.
Results: 125 pregnant women (43 with IBD) and 79 babies (26 born to mothers with IBD) were included; 193 maternal samples (148 stool, 45 placenta) and 245 infant stool samples were analyzed. Among all babies, 35.4% were born via C-section and 96% were full-term. Even though 74% of women with IBD were in remission throughout pregnancy, this group presented lower bacterial diversity (p=0.001, ANOVA), and different overall bacterial composition in stool (p=0.001; PERMANOVA, unweighted Unifrac), with enrichment in Gammaproteobacteria and a decrease in Bacteroidetes. Mothers with IBD presented differences in the overall composition of their placental microbiome (p=0.001) with a decrease in Firmicutes, and expansion in Alphaproteobacteria and Actinobacteria. Babies born to IBD mothers showed a different stool bacterial composition (p=0.001), that persisted over time, with expansion of Gammaproteobacteria and a reduction in Actinobacteria taxa, differences that were independent of mode of delivery (Figure).
Conclusions: IBD women maintain dysbiosis in their gut microbiota during pregnancy, and present with different placental microbiome. Babies born to mothers with IBD demonstrate different gut microbiome composition that persists for up to 3 months of life, and is independent of mode of delivery. These findings suggest that maternal IBD status affects the gut microbiome composition in offspring, which could contribute to future disease risk.