Children of mothers with inflammatory bowel disease (IBD) face a higher risk of developing IBD, likely due to early-life changes in the gut microbiota. New research shows that, after age four, children born to mothers with IBD develop distinct gut microbiotas that can weaken gut barrier function and alter immune-related metabolism.

The findings, published in Med, suggest that changes in gut bacteria raise a child’s chances of developing IBD later in life, offering clues to why the conditions sometimes runs in families.

Scientists have known that the gut microbiota plays a critical role in shaping immune system development. During the first few years of life, a child’s microbiota evolves and stabilizes into a more adult-like composition.

Recent studies showed that newborns of mothers with IBD have altered gut bacteria, but it remains unclear whether these changes persist as children grow.

Jantien Wieringa at Erasmus MC University Medical Center in Rotterdam, the Netherlands, and her colleagues studied gut bacteria from 44 children of mothers with IBD and 44 children of healthy mothers.

Microbiota differences

Mothers with IBD were more likely to use antibiotics after delivery and less likely to breastfeed, and their children had slightly lower birth weights. Analysis of gut bacteria showed that mothers with IBD had different microbial communities compared to healthy mothers, and gut bacteria were more alike between mothers with IBD and their children than between healthy mothers and their children.

Children of IBD mothers also higher levels of Clostridium in their guts compared to children of healthy mothers, the researchers found.

Over time, the overall diversity of gut bacteria increased in both groups of children and stabilized around three or four years of age. However, after age four, children of mothers with IBD showed microbial differences, including higher bacterial richness and an increase in Alistipes bacteria.

Disease heritability

To see if these changes could cause gut inflammation, the researchers transplanted fecal samples from four-year-olds into germ-free mice. The mice developed microbiotas similar to the human donors, and while animals receiving gut bacteria from children of mothers with IBD had some metabolic differences compared to those receiving gut bacteria from children of healthy mothers, they showed no signs of inflammation or increased immune activity.

However, mice that received gut microbes from children of mothers with IBD showed weakened gut barrier function and altered immune-related metabolism. In particular, the production of kynurenine — a molecule important for immune regulation — was lower due to reduced activity of a specific intestinal enzyme. 

The findings suggest that these microbial changes may increase long-term susceptibility to IBD, the authors say. “Our findings provide further support for the role of the gut microbiome in the pathogenesis of IBD and may explain part of the maternal heritability of the disease.”