Ulcerative colitis is a condition that is characterized by chronic inflammation of the colon. It is an important pediatric disease as 25% of all cases begin in childhood and its incidence is steadily increasing. It carries considerable morbidity and shortened life expectancy. Current therapies are suboptimal as some therapies are associated with high failure rate while others are associated with significant drug toxicity. 5-ASA is considered first line of therapy in mild to moderate disease. UC is believed to be related to a genetically and environmentally-generated altered immune response to the enteric microbiome. Previous work in the PI laboratory suggests that children with UC harbor a unique gut microbial profile, which can predict therapeutic response. Therefore, modifying the gut microbiome may provide therapeutic benefit. However, attempts to modify the gut microbiome were largely unsuccessful until the advent of fecal transplant for treating colitis. Fecal microbiota transplant (FMT) has been introduced several decades ago in an attempt to restore the gut microbial balance and it appears to be a more efficient method to safely and effectively change and sustain the gut microbial composition. To this date there have been a number of successful case reports in ulcerative colitis, to suggest control of disease activity and a cure in some cases However, there has not been uniform success reported for the use of FMT, especially in severe cases recalcitrant to medical therapy. Thus, it has been difficult for the scientific community to embrace this therapy, especially in children, as there have been no controlled pediatric studies published to this date. Therefore, there is a strong need to determine the safety and efficacy of FMT in treating UC in prospective, randomized pediatric clinical trials. We hypothesize that children with ulcerative colitis will respond to fecal transplant therapy which will modify their gt microbial profile. We propose a randomized, double- blinded, controlled study to evaluate the safety and efficacy of fecal microbial transplant from healthy donor versus placebo FMT (child's own stool) in combination with 5-ASA in inducing mucosal healing in mild to moderate disease in children with ulcerative colitis. We also propose studying the effect of transplant on gut microbial profile using advanced molecular tools. Results of this study will help us understand the mechanism by which the gut microbiome contributes to this disease and examine the viability and durability in FMT recipients with a potential paradigm shifting for ulcerative coliti treatment in children.
Ulcerative colitis is a chronic, life-long, debilitating condition that frequently affects children and is strongly linked to the gut organisms. Current treatment options are limited and carry significant side effect potential. We have assembled a strong team of researchers to investigate the safety and therapeutic potential of stool transplant in this disease and study how it influences the intestinal microbes.
