Inflammatory bowel diseases (IBDs) show an increasing incidence worldwide, especially in children. Although a positive family history—especially when it comes to maternal IBD—is a strong risk factor for developing IBD later in life, whether the gut microbiome in mothers with IBD shapes the offspring’s microbiome, involving immune responses, remains to be seen.
A prospective cohort study in Gut, led by the senior author Dr. Inga Peter at Icahn School of Medicine at Mount Sinai in New York, has found that an altered gut microbiota composition persists during pregnancy with IBD and alters the infant stool microbiota, which triggers changes in the adaptive immune system in germ-free mice.
First, the authors characterized the gut microbiota composition of pregnant women with and without IBD at first, second and third trimester and of their offspring at days 7, 14, 30, 60 and 90 after birth (73 mother-infant dyads in total).
An altered overall gut microbiota composition (b-diversity) was found both in pregnant women with IBD across all three trimesters and their offspring, as compared with control pregnant women and their children.
Differences in gut microbiota composition in mothers with IBD compared to mothers without IBD were driven by a depletion in the relative abundance of Bacteroidetes and an increase in the relative abundance of Proteobacteria. Likewise, babies born to mothers with IBD showed a gut microbiota enriched in Gammaproteobacteria— linked to intestinal inflammation and IBD—and depleted in Bifidobacteria—a gut commensal used as a probiotic for managing mild to moderately active ulcerative colitis. Notably, reduced bacterial diversity in the offspring of mothers with IBD was apparent as early as the end of the first week of life and persisted for the duration of the 3-month study.
Maternal IBD was the factor with the strongest capacity to predict infant gut microbiota diversity and variation. Other factors that affect offspring gut microbiota composition include delivery, feeding behavior, preterm birth and exposure to antibiotics.
Second, the authors compared how the maternal and infant gut microbiota shape immune responses in the colonic lamina propria and mesenteric lymph node of germ-free mice. To that end, germ-free mice were inoculated with the maternal and infant stool microbiota, and innate and adaptive immune cells in the murine intestines were profiled.
The transfer of stool microbiota from third-trimester mothers with IBD and their 90-day-old children led to reduced microbial diversity and fewer class-switched memory B cells and regulatory T cells in the murine colonic lamina propria and lymph node. Those findings suggest IBD-related altered gut microbiota is involved as a driver of altered adaptive immune responses in colonic homeostasis.
On the whole, the current findings support the effect of maternal IBD not only on gut microbiota composition during pregnancy, but also on the offspring’s gut microbiota. It is also interesting to note that, according to the mice data presented, a mechanism explaining the findings may involve fewer class-switched memory B cells and regulatory T cells in the colon. As such, further validation in large cohorts of mother-infant dyads for longer follow-ups may be worthwhile.
Torres J, Hu J, Seki A, et al. Infants born to mothers with IBD present with altered gut microbiome that transfers abnormalities of the adaptive immune system to germ-free mice. Gut. 2020; 69:42-51. doi: 10.1136/gutjnl-2018-317855.