Mechanistically, inflammatory bowel diseases (IBD), principally Crohn’s disease (CD) and ulcerative colitis (UC), are considered a consequence of dysregulated interplay between host genetic-susceptibility and immunity, the enteric microenvironment, and environmental “triggers”, but the specific interactions that lead to IBD are unresolved. The early life environment, when the microbiome and immune function are established, may dictate IBD-risk later in life. The microbiome of IBD is characterized by expansion of ‘aggressive’ Proteobacteria and E. coli, relative to depleted ‘protective’ Firmicutes. E. coli strains that adhere to and invade epithelial cells and replicate in macrophages in vitro (AIEC), have been isolated from 21-63% of patients with CD. AIEC can exploit defects in intracellular killing conferred by CDrisk polymorphisms, elicit Th1/Th17 immune responses and induce colitis in genetically susceptible dogs and mice, suggesting causal involvement in IBD. However, as E. coli, including AIEC, is also linked to protective immunity, it is considered a symbiont and opportunistic pathogen (summarized in PMID: 35413017).

The host and bacterial factors related to the acquisition and intestinal colonization of infants by E. coli and AIEC are unresolved. E. coli has emerged as a neonatal colonizer across species, and mothers and babies with IBD have been found to harbor a less diverse microbiome enriched in E. coli relative to controls (PMID: 31036757). Babies from mothers with IBD also have higher levels of fecal calprotectin, a marker of intestinal inflammation, than babies born to mothers without IBD, suggesting dysbiosis may be driving inflammation (PMID: 33307026). This notion, and the potential for infant microbiota to imprint the intestinal immune system, is supported by the ability of stools from dysbiotic infants to reduce classswitched memory B cells and regulatory T cells in the colon of germ free mice (PMID: 33307026). The enrichment in E. coli sequences within the dysbiotic consortium of immuno-active infant stool bacteria suggests AIEC may be involved. However, the type of E. coli colonizing neonates and their mothers, their source, and the role of maternal IBD, mode of delivery and infant nutrition before weaning are unclear.

It is against this background that we propose to determine the relationship of E. coli strains present in feces and vaginal smears of mothers with and without IBD in the last trimester to E. coli strains in infant feces at 7 days and pre-weaning.

We anticipate this study will advance knowledge of, i) the relatedness of E .coli strains in infants and mothers, and the effect of mode of delivery, ii) the number, phylogeny and pathotype of E. coli in stools of infants born to mothers with and without IBD and their relationship to intestinal inflammation (calprotectin),  the differential ability of infant and maternal E. coli strains to utilize enteric substrates and milk sugars for growth. This study will establish an archive of E.coli strains to facilitate future longitudinal studies of E. coli phylogeny, pathotype and metabolism as they evolve with age and onset of IBD in this clinical cohort.