Infants born to mothers with IBD present with altered gut microbiome that transfers abnormalities of the adaptive immune system to germ-free mice

Joana Torres, Jianzhong Hu, Akihiro Seki, Caroline Eisele, Nilendra Nair, Ruiqi Huang, Leonid Tarassishin, Bindia Jharap, Justin Cote-Daigneault, Qixing Mao, Ilaria Mogno, Graham J. Britton, Mathieu Uzzan, Ching Lynn Chen, Asher Kornbluth, James George, Peter Legnani, Elana Maser, Holly Loudon, Joanne StoneMarla Dubinsky, Jeremiah J. Faith, Jose C. Clemente, Saurabh Mehandru, Jean Frederic Colombel, Inga Peter

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Background and aims Prenatal and early life bacterial colonisation is thought to play a major role in shaping the immune system. Furthermore, accumulating evidence links early life exposures to the risk of developing IBD later in life. We aimed to assess the effect of maternal IBD on the composition of the microbiome during pregnancy and on the offspring's microbiome. Methods We prospectively examined the diversity and taxonomy of the microbiome of pregnant women with and without IBD and their babies at multiple time points. We evaluated the role of maternal IBD diagnosis, the mode of delivery, antibiotic use and feeding behaviour on the microbiome composition during early life. To assess the effects of IBD-associated maternal and infant microbiota on the enteric immune system, we inoculated germ-free mice (GFM) with the respective stool and profiled adaptive and innate immune cell populations in the murine intestines. Results Pregnant women with IBD and their offspring presented with lower bacterial diversity and altered bacterial composition compared with control women and their babies. Maternal IBD was the main predictor of the microbiota diversity in the infant gut at 7, 14, 30, 60 and 90 days of life. Babies born to mothers with IBD demonstrated enrichment in Gammaproteobacteria and depletion in Bifidobacteria. Finally, GFM inoculated with third trimester IBD mother and 90-day infant stools showed significantly reduced microbial diversity and fewer class-switched memory B cells and regulatory T cells in the colon. Conclusion Aberrant gut microbiota composition persists during pregnancy with IBD and alters the bacterial diversity and abundance in the infant stool. The dysbiotic microbiota triggered abnormal imprinting of the intestinal immune system in GFM.

Original languageEnglish
Pages (from-to)42-51
Number of pages10
JournalGut
Volume69
Issue number1
DOIs
StatePublished - 1 Jan 2020

Keywords

  • early life microbiome
  • inflammatory bowel disease
  • pregnancy

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