Understanding how Crohn’s Disease treatments affect children’s gut microbiome
Researchers have discovered that different treatments for Crohn’s disease have varying effects on the gut microbiomes of children and teens—a finding with implications for approaches to monitor treatment response and for potential development of future microbiome-targeted therapies. People with Crohn’s disease experience abdominal pain, diarrhea, and intestinal bleeding, and children may possibly experience stunted growth as well. Current treatments include antibiotics, immunomodulators, biologic therapies, and defined formula diets. It is known that the composition of the gut microbiome is altered in people with Crohn’s disease: there are differences in which microbes are present, and at what levels. This observation suggests that the microbiome may play a role in the disease. However, it is not known how current Crohn’s disease treatments affect the composition of the gut microbiome, and whether treatments restore the composition seen in healthy people. This knowledge could help scientists better understand the mechanisms by which current therapies exert their effects, thereby enabling development of more effective therapeutic strategies to improve the health and quality of life of people with Crohn’s disease.
Toward this goal, researchers analyzed fecal samples from 85 male and female children and teens with Crohn’s disease who were just starting treatment with immunosuppressive medicine or a defined formula diet, and compared them to samples from 26 healthy young people. They examined symptoms, inflammation, and changes in the gut microbiome over 8 weeks, and found that each treatment had a different effect on the composition of the gut microbiome. Treatment with the formula diet—with 90 percent of daily calories coming from the formula—substantially changed the gut microbiome within just 1 week. By 8 weeks of treatment, those who experienced benefits of the treatment—measured as reduced inflammation—had a gut microbiome that still differed from a healthy microbiome, but not by as much. In individuals who did not have therapeutic benefit, the microbiome became even more imbalanced than it was before therapy started. Additionally, after 1 week of treatment with the formula diet, the composition of the gut microbiome differed between children who ultimately responded to treatment and those who did not, suggesting that measures of the microbiome may be useful to predict who will respond. Immunosuppressive therapy, with a compound called anti-TNFalpha, was found to reduce inflammation and cause the gut microbiome to become somewhat more similar to that in healthy children, although it was still altered. This finding suggests that it is possible to achieve a therapeutic effect without restoring an entirely normal microbiome. Some of the study participants were also on antibiotics, which kill bacteria. The researchers found that, apart from the effects of other treatments, antibiotic use altered bacterial species and increased levels of fungi in the gut.
Overall, the scientists found that Crohn’s disease treatments had distinct effects on the gut microbiome, and none of them fully restored the normal balance of gut microbes seen in healthy youth. These findings could open up new avenues for developing treatments for manipulating the microbiome to benefit people with Crohn’s disease. They may also potentially be used to predict who will respond to different therapies, toward a longer-term goal of personalizing treatments.