Other environmental factors also may play a role, study presented at DDW finds
By Amy Ratner, director of scientific affairs
Breastfeeding in early infancy, the amount of gluten a baby consumes daily, as well as nationality, sex and birth order are environmental factors that influence whether at-risk children go on to develop celiac disease, a study presented recently at Digestive Disease Week (DDW) found.
These environmental factors, particularly breastfeeding, influence the development of the community of microorganisms in the gut, called the microbiome, and may be the underpinning of why some at-risk children get celiac disease while others do not.
The research was based on data collected in the Celiac Disease Genomic Environmental Microbiome and Metabolomic Study (CD GEMM), which has enrolled 550 at-risk children and is following them from birth to five years, with the option of extending participation to 10 years.
Children who have a parent or sibling with celiac disease are considered at risk. The children in the GEMM study live in 42 states and eight regions in Italy. This study included 423 of the children and analyzed how environmental factors affected the group overall and when looking at the American and Italian children separately.
Researchers from Massachusetts General Hospital, the Buck Institute for Research on Aging and colleagues in Italy and Canada set out to determine how external environmental factors and the internal microbiome environment influence whether children in study have protections from developing celiac disease or if they are more likely to develop it. They analyzed data from questionnaires filled out by parents and stool and blood samples collected from the children.
Environmental factors included nationality, whether a child was breastfed in the first six months, how much gluten a child consumed daily from 12 to 15 months, sex and birth order.
Of 219 children from the United States, 23 went on to develop celiac disease, while 33 of 204 Italian children were diagnosed with the condition. Consequently, there was a higher risk of celiac disease in Italian children compared to American children, said Max Manwaring-Mueller, a researcher at the Buck Institute, who presented the study results.
Although breastfeeding overall appeared protective when all the children were considered, the effect was more pronounced when analyzed in in Italian children alone, the study showed. Of the Italian children, 25 percent of those who were not breastfed developed celiac disease compared to 11 percent who were. Among American children, 14 percent who were not breastfed developed celiac disease compared to about 9 percent who were.
Researchers were surprised to see breastfeeding come up as protective against developing celiac disease because there have been mixed results in other studies, said Maureen Leonard, MD, a study author and director of the Center for Celiac Research and Treatment at Massachusetts General.
“Our goal is to now connect this finding with specific changes in the microbiome and then perform mechanistic studies to understand how the specific species and strains identified may protect against loss of tolerance,” she said.
Among other environmental factors, a stronger protective effect was found in male children and younger children compared to their first-born sibling. Additionally, children who ate higher quantities of gluten from the ages of 12 to 15 months had a greater risk of developing celiac disease. “If the environmental trigger is gluten, and you are exposed to more gluten, there are more opportunities to have that conversion event [from not having celiac disease to having celiac disease],” Manwaring-Mueller said.
This finding is in line with other studies that have found increased consumption of gluten in early life may increase the risk of celiac disease, Leonard said. She noted that it’s not yet clear whether increased gluten in an at-risk child’s diet simply accelerates the age at which the child develops celiac disease and ultimately the same number of children will develop it, or if the risk is actually increased.
“Our research cannot answer that question, but a prospective study looking at gluten intake beyond 12 months of age – which hasn’t been done yet – could,” she said. “The main takeaway here is that increased gluten in early life may increase the risk or accelerate the development of celiac disease but more work needs to be done to understand how much gluten is needed to see these outcomes.”
In addition to the environmental factors, distinct microbiome signatures differentiate those who convert to have celiac from those who don’t,” according to Manwaring-Mueller. Higher levels of some bacteria and lower levels of others play a role.
He said his interest in working with Leonard and the GEMM study data stemmed from his own diagnosis three years ago. More broadly, he said, his diagnosis led to his interest in how the external environment can interact with the internal environment and the microbiome influence whether someone gets celiac disease.
DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Studies presented at DDW are sometimes preliminary and give an early look at investigations that are likely to include more details as they progress toward publication in a peer reviewed scientific journal.
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