Study Shows that Different Treatments for Children with Crohn’s Disease Do Not Entirely Restore Healthy Gut Microbiota

Study Shows that Different Treatments for Children with Crohn’s Disease Do Not Entirely Restore Healthy Gut Microbiota

In a recent study published in the journal Cell Host & Microbe, a team of researchers from the University of Pennsylvania performed an analysis of the gut microbiota of children treated for Crohn’s disease, with results showing that diet and anti-inflammatory treatments can change different components of the gut microbial population without completely re-establishing the natural stability of gut bacteria and fungi. These unexpected results could lead to the development of novel strategies for the diagnosis and treatment of patients with inflammatory bowel diseases (IBD).

“We show that microbes in the gut respond to treatment of inflammatory bowel disease in a much more complex way than has been previously appreciated,” said co-principal investigator Dr. Gary Wu in a news release. “The results of our study provide information that could be used to track or predict disease, as well as new diet-based therapeutic strategies.”

The human gut microbiota is densely populated by microbes from all three domains of life together with viruses. Crohn’s disease results from a pathologic interaction between the mucosal immune system and the environment, particularly the microbiota residing in the gut lumen, and is characterized by altered — or “dysbiotic” — gut bacterial composition.

Early onset of Crohn’s disease in children can lead to problems including a delay in puberty, weak bones, and stunted growth. These patients usually receive treatment with antibiotics, anti-TNF (an anti-inflammatory drug), or with a restrictive diet that may involve tube feeding.

In the study entitled “Inflammation, Antibiotics, and Diet as Environmental Stressors of the Gut Microbiome in Pediatric Crohn’s Disease”, the team of researchers led by Dr. Wu and colleagues Drs. James Lewis and Frederic Bushman of the University of Pennsylvania and their international associates, examined 90 children with a diagnosis of Crohn’s disease who were receiving treatment with a formula-based diet or anti-TNF therapy. Researchers compared these children with 26 healthy controls. Fecal samples were analyzed with shotgun metagenomic sequencing.

The results revealed that patients who responded to treatment exhibited different changes in the composition of the gut microbiota in comparison to non-responders, indicating that assessment of the gut microbe community could be used to predict treatment responses. Furthermore, antibiotics, anti-TNF, and formula-based diet treatments were found to have different effects on the abundance of different gut microbe types. Remarkably, none of the therapies was found to completely re-establish the regular gut microbiota balance.

More specifically, the results revealed that:

  • Inflammation, antibiotics, and diet independently affect microbiota in Crohn’s disease;
  • Antibiotics are associated with bacterial dysbiosis and increased fungi;
  • Dysbiosis decreases with reduction in intestinal inflammation;
  • Diet has an independent and rapid effect on gut microbiota composition.

“These data are a step to trying to identify ways to manipulate the gut microbiome to provide favorable outcomes to patients with Crohn’s disease,” said the study’s first author, Dr. James Lewis. “We observed that upon initiation of a therapeutic formula-based diet, the gut microbiota look even less similar to that of a healthy child, suggesting that one does not have to necessarily give back the healthy microbiota to have a therapeutic effect. It is possible that the effect of the formula diet is through mechanisms other than altering the microbial community.”

The research team plans to explore further therapeutic formula-based diets. “We hope to use this information to develop diets that are less restrictive but equally effective, or medications that mimic the mechanisms of the formula-based diets,” Dr. Lewis concluded. “We also hope to study other diets that are popular among patients with Crohn’s disease in the coming years.”

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