Pai Laboratory Research Overview

Children with ulcerative colitis harbor unique bacteria in their intestines that differ from those of healthy children. Researchers believe these microbial imbalances may contribute to disease activity.

The Pediatric Fecal Microbiota Transplant for Ulcerative Colitis (PediFETCh) study team led the first multicenter pilot randomized controlled trial of fecal microbiota transplantation in children with ulcerative colitis. The trial evaluated whether fecal microbiota transplantation (FMT) from healthy donors could help restore a healthier gut environment and improve clinical outcomes in pediatric patients with active ulcerative colitis.

Related publication

Results of the First Pilot Randomized Controlled Trial of Fecal Microbiota Transplant In Pediatric Ulcerative Colitis: Lessons, Limitations, and Future Prospects. Gastroenterology. August, 2021.

Building on the PediFETCh trial, the Pai Lab completed a multicenter pilot randomized controlled trial evaluating fecal microbiota transplantation in children with Crohn's disease.

This study investigates whether fecal microbiota transplantation (FMT) can help modify gut microbial composition, reduce intestinal inflammation, and improve symptoms in patients with pediatric Crohn's disease who have limited treatment options. The trial employed a novel design to administer a combination of colonoscopic, rectal enema, and oral FMT capsule-delivered stool from healthy donors. These findings will inform the safety, feasibility, and early efficacy of FMT for future larger trials.

Related Publication

Protocol for a Double-blind, Randomised, Placebo-controlled Pilot Study for Assessing the Feasibility and Efficacy of Faecal Microbiota Transplant in a Paediatric Crohn's Disease Population: PediCRaFT Trial. BMJ Open. November 2019.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a rapidly increasing chronic liver disease in children, closely linked to rising rates of pediatric obesity. This disease is projected to become the leading cause of liver transplantation across North America in the next two-three decades.

Fiber supplements, like inulin-enriched fructooligosaccharides, represent a promising therapeutic bridge between nutrition and the microbiome, serving as a safe, low-cost option to support beneficial gut bacteria. The development and progression of MASLD has been associated with changes in gut bacteria, and earlier studies demonstrated that fiber supplementation may help children with obesity and fatty liver disease.

The FIND (Soluable Fibre Supplementation in Non-Alcoholic Fatty Liver Disease) trial is a five-year, grant-funded, multicenter randomized controlled trial between CHOP and McMaster Children's Hospital (Hamilton, Canada) supported by the Canadian Institutes of Health Research. The Pai Lab will evaluate whether inulin-enriched fructooligosaccharide can improve glycemic control, reduce liver fat, and modify metabolic outcomes in children with MASLD. The team is excited to explore how nutritional interventions can serve as low-cost, scalable treatments for children living with this chronic liver condition.

The Pai Lab is actively investigating novel biomarkers to better diagnose, risk-stratify, and monitor children with metabolic dysfunction-associated steatotic liver disease (MASLD). Using a combination of microbiome profiling, metabolomics, and a novel blood-based proteomics platform, the lab aims to develop more personalized, targeted approaches to diagnosing, prognosticating, and managing pediatric fatty liver disease and its metabolic complications.

Children with cystic fibrosis (CF) face lifelong challenges related to malabsorption and gastrointestinal dysfunction. The Pai Lab is studying how existing CF treatments—specifically the use of proton-pump inhibitors that inhibit gastric acid release—impact gut microbiota, nutrient absorption, and metabolic outcomes. This work may help guide future nutritional strategies to optimize gut health, support long-term health in this population, and challenge existing paradigms about what is required to optimize fat absorption in this population.

Necrotizing enterocolitis (NEC) remains a leading cause of intestinal failure and short bowel syndrome in premature infants.

The Pai Lab will collect biological samples from infants at risk for NEC for the NeoGut biobank, an innovative multidisciplinary project involving the Divisions of Neonatology, General Surgery, and Gastroenterology, as well as the Intestinal Rehabilitation Program at CHOP.

This long-term initiative will leverage the CHOP Biobank and the Biorepository Core, supporting translational research into the pathogenesis, prevention, and management of NEC. This condition, the leading cause of short bowel syndrome in the pediatric population, carries an extremely high morbidity and mortality in neonates. The Pai team aims to identify the underlying cause of this disorder and ultimately find ways for earlier diagnosis and treatment of this condition.

The Pai Lab is exploring how early-life feeding practices may influence the development of allergic and atopic diseases (such as food allergies, eczema, and asthma) in children with short bowel syndrome.

These studies investigate the complex interplay between gut adaptation, immune development, and the microbiome, with the goal of informing better long-term management strategies for these high-risk patients. This initiative is being conducted in partnership with the Division of Allergy and Immunology, and the Intestinal Rehabilitation Program through the Division of Gastroenterology.

The Pai Lab leads multiple Health Canada-approved clinical trials of fecal microbiota transplantation (FMT) in non-inflammatory bowel disease conditions.

FMT is being studied in anorexia nervosa as a potential intervention to support metabolic recovery, improve gut-brain interactions, and optimize the efficacy and durability of nutritional rehabilitation in adolescents with severe restrictive eating disorders.

The FMT for Anorexia Nervosa trial will utilize the McMaster Children's Hospital Pediatric Donor FMT Stool Bank, the first of its kind in Canada and developed under the leadership of Drs. Nikhil Pai, Fariha Chowdhury, Jeffrey Pernica, Christine Lee, Paul Moayyedi, and Michael Surette. FMT materials will be developed into oral lyophilized capsules, to be taken in oral capsular form instead of invasive rectal enema or colonoscopic delivery forms, which can be painful, and at the least, uncomfortable.

FMT is being evaluated as a strategy to correct microbial dysbiosis and improve malabsorption in children with short bowel syndrome complicated by small intestinal bacterial overgrowth (SIBO). Several small case reports have been previously published on this approach. This pilot feasibility study, FMT for the Treatment of SIBO aims to be the largest case series in pediatrics, and will be a multi-center open-label pilot study between Toronto SickKids Hospital and McMaster Children's Hospital.