Early indicators of Pre-IBD Phenotype in Mice following Fecal Microbiota Transplant from Children of IBD-Affected mothers - mice cohort

Abstract Objective Inflammatory bowel disease (IBD) carries a hereditary risk, which is stronger along the maternal than the paternal line. Infants born to mothers with IBD have an altered microbiome in early life, but whether this persists later in life and contributes to IBD risk is unknown. Design Fecal microbiome was analyzed in samples collected from 26 women with IBD and 44 of their infants ranging from 0-10 years of age. 44 age-matched children born to 29 women without IBD served as controls. Fecal microbiota transplantation (FMT) was carried out from 4-year-olds born to IBD and control mothers to germ-free mice and markers of inflammation, barrier function and metabolic changes were investigated. Results Intestinal microbiomes were more similar between women with IBD and their children, than between control mothers and their offspring. Microbial changes start to be noticeable in children from mothers with IBD from the age of 4 years and above. No inflammatory response was present in mucosa of mice receiving FMT from children born to mothers with IBD. However, mesenteric lymph node enlargement and decreased expression of barrier genes Zo1 and Ocln were seen in mice receiving FMT from infants from mothers with IBD compared to controls. Additionally, reduced colonic expression of the immunological tolerance enzyme Ido1 coincided with decreased serum kynurenine/tryptophan ratios. Conclusion Fecal microbiomes of children born to mothers with IBD retain characteristics which reduce epithelial barrier function and tolerogenic tryptophan metabolism. A microbiome-induced pre-IBD phenotype may contribute to an enhanced IBD predisposition in infants born to mothers with IBD.