The Role of Gut Microbiome in Predicting Comorbidities and Complications in Children With Inflammatory Bowel Disease

Overview

Background: Bacteria and other microorganisms that live in the intestines (the gut microbiome) play an important role in a person s health. The gut microbiome helps to regulate the immune system and control inflammation. Imbalances in the gut microbiome have been linked to illnesses such as inflammatory bowel disease (IBD). People diagnosed with IBD can have serious health problems. Researchers want to know more about how the gut microbiome affects the development and progression of IBD in children. In this natural history study, they will compare the gut microbiomes of healthy children with those who have IBD. Objective: To collect stool and samples of intestine tissue from children with and without IBD undergoing colonoscopy. Eligibility: People under 21 years old who are having a colonoscopy at the Inova Health System or Pediatric Specialists of Virginia. Design: Participants will fill out a questionnaire. They will answer questions about their history. Topics may include how they were fed as infants; how they were born; and how often they took antibiotics. Stool and tissue samples from the intestines will be taken during the participants colonoscopy. They may also give samples of blood and urine. Participants may be asked to provide additional stool, blood, and urine samples. They may do this up to 3 times per year. These samples may be collected at the clinic; they may also be collected at home and mailed to the researchers. If they have more colonoscopies, participants may be asked for more tissue samples. Participants will be enrolled for up to 10 years. ...

The gut microbiome (community of microorganisms in the intestines) serves many important roles in healthy people, including immune system regulation and anti-inflammatory functions. A dysbiosis (imbalance) in the gut microbiome is associated with many immune mediated diseases, including inflammatory bowel disease (IBD). The microbiome is thought to play a central role in the development and propagation in IBD. Studies have shown that in IBD, the gut microbiome demonstrates increased pro-inflammatory bacteria, a reduction in anti-inflammatory bacteria and overall reduced diversity. Inflammatory bowel disease is complicated and comes at a high burden to those affected. While affecting both children and adults, patients diagnosed before 18 years of age often have more severe phenotypes than those diagnosed in adulthood. Patients affected by IBD often have many complications such as linear growth failure, decreased bone mineral indices, delayed puberty, malnutrition and need for surgeries. At this time, we have limited ability to predict which patients will go on to develop complications and the time points in which these may occur. Further, there are many comorbidities present in patients with IBD including dermatologic manifestations, hepatobiliary disease, other immune-mediated disease such as celiac disease as well as endocrinopathies. Children with IBD and these comorbid conditions are thought to have higher morbidity and decreased quality of life. While the gut microbiome is thought to mediate the development of many of these diseases, there is little literature associating clinical and microbiome drivers of those with IBD and these additional comorbidities. Given that the microbiome may have a role in potentiating the inflammatory pathways contributing to IBD, there is potential to identify microbial signatures to help determine disease outcomes such as complications and response to treatment. In this study, we intend to examine differences in the microbiome diversity and composition in children with IBD and controls. We will then follow subjects longitudinally to determine initial microbiota signatures and changes for those who develop comorbidities, complications and therapy responsiveness. We hope that by elucidating the microbiome of these children, we will have the opportunity to better understand the pathogeneses of co-morbid diseases, ultimately enabling the development of microbiome-based therapeutics for these conditions.