Composition, Function, and Role of the Intestinal Microbiome in Pediatric Heart Failure and Heart Transplantation
Abstract
This proposal addresses the Fiscal Year 2017 Peer Reviewed Medical Research Program Topic Areas of Congenital Heart Disease and Diarrheal Disease. There are emphases on the following Areas of Encouragement: (1) the health outcomes of individuals with congenital heart disease across their life spans and (2) the relationship between existing gastrointestinal flora (microbiome) and the susceptibility, duration, and severity of diarrheal disease. We address multiple Topic Areas and Areas of Encouragement by planning to characterize the gastrointestinal flora (microbiome) in children and young adults with congenital heart disease or heart transplant. Our main goal is to determine if these patients have changes in their microbiome, and if so, if these changes are related the development of diarrhea and poor health outcomes. Our long-term goal is to develop and test innovative treatments that prevent and repair harmful changes to the microbiome to improve diarrhea and poor health outcomes for children and young adults with congenital heart disease that will require or have already undergone heart transplant. Congenital heart disease is the most common birth defect in the United States. However, there is no cure for several forms of congenital heart disease, and many affected children and young adults eventually require a heart transplant for survival. Unfortunately, many of these patients subsequently experience and suffer from transplant related medical problems. Over 90% of adult heart transplant patients have gastrointestinal symptoms and over 50% experience frequent diarrhea. Pediatric heart transplant patients are commonly affected as well. This is significant because diarrhea and other gastrointestinal symptoms increase the risk of death in heart transplant patients. Disappointingly, long-term survival for heart transplant patients has still not improved despite advances in medical care and technology. Innovative research that can improve prevention, diagnosis, and treatment of heart transplant-related diarrhea and other heart transplant-related medical problems has the significant potential to improve the quality of life and survival in these patients. A healthy microbiome is important for overall health and is specifically important for the normal functions of the gastrointestinal and immune systems. Changes to a healthy microbiome can increase the risk of diarrhea and play a significant role in infection, inflammation, gastrointestinal disease, and cancer. Many of the required medications that heart transplant patients take can cause microbiome changes. However, no previous research has studied if the microbiome is altered in children and young adults with congenital heart disease or heart transplant, and if so, what the effects are. Our proposal plans to determine what kinds of microbiome changes have occurred and what the effects of these changes are. We strongly suspect that the microbiome is significantly altered in heart transplant patients. Harmful changes to the microbiome can increase the risk of infection and diarrhea, which both increase the risk of death in heart transplant patients. We therefore strongly believe that maintenance of a healthy microbiome is of paramount importance to the survival of children and young adults with congenital heart disease that will require or have undergone heart transplant. To successfully prevent or treat harmful changes to the microbiome in these patients, we first have to perform microbiome analysis, which is done on patient stool specimens. We then have to determine what microbiome changes occur and then investigate if specific changes are predictive of or responsible for complications. This will require the sequential collection of stool specimens from patients prior to heart transplant, after heart transplant, and during episodes of transplant-related complications such as diarrhea, infection, and rejection of the donor heart. That is precisely w
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810557
Entities
People
- Joseph Spinner
Organizations
- Baylor College of Medicine
- United States Army