A Saint Louis University School of Medicine scientist and SLUCare physician has received funding from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH) to study Short Bowel Syndrome (SBS).
Ajay Jain, M.D., professor of pediatrics, pharmacology, and physiology, received a highly coveted NIH R21 grant for $428,020. This round of funding compliments Jain's recent NIH R01 grant for $1,893,750. With these two grants, Jain is focusing on comprehensively assessing gut-systemic signaling and the role of gut microbiota in preventing injury in SBS.
SBS is a devastating condition where bowel resection results in insufficient intestines to sustain a patient's nutritional needs through regular feeding. Such patients, Jain said, require intravenous nutrition through a complicated process called Total Parenteral Nutrition (TPN), many with lifelong dependence.
Tens of thousands of patients worldwide require continuous TPN for survival. Unfortunately, a large portion of SBS patients are children, infants and newborn babies. Despite the lifesaving benefits of this widely used therapy, patients with SBS may have significant side effects including Intestinal Failure Associated Liver Disease (IFALD). IFALD leads to progressive liver failure as well as gut injury, permeability changes, and atrophy, Jain said.
"There are no established treatment strategies for SBS, and patients suffer extensive morbidity and need intensive medical management, with many patients dying or requiring a multi-visceral transplant for survival," he said. "Thus, this remains a major research focus in gastroenterology and hepatology.
"There has been intense research in this area throughout the world and while several ideas have been proposed we wanted to 'think outside the box.'"
Jain hopes to leverage results from his lab's earlier studies that highlight the role of altered gut-derived signals as a major driver of injury in SBS. This current round of funding will explore how gut microbes influence the disease progression in SBS.
Each person carries over 100 trillion microbes. In terms of genetic material, the microbiome genome is a hundred-fold higher than that of its host, which means that from a genetic perspective each of us is only 1% human and 99% bacteria.
Our goal is to understand the impact of these bugs, isolate the good organisms for treatment, and restore key signaling pathways, which could bring a paradigm change in the management and care of some of our most vulnerable and precious patients."
Ajay Jain, M.D., professor of pediatrics, pharmacology, and physiology, Saint Louis University School of Medicine
This NIH grant will also evaluate the impact of bacterial breakdown products and novel signaling molecules that Jain and his lab have been studying in preclinical models, testing their efficacy in mitigating the multisystem injury in SBS. He will explore new microbial driven signaling pathways that would open strategic areas of therapeutic targeting.
Jain will also use organoid approaches, which is a highly specialized technique where organs are grown in the lab to gain further insights.
"We believe that we are on the verge of creating sustainable options for our sickest patients with SBS. Our cutting-edge translational research could prove transformative not only as a treatment but advance science in unlocking the mysteries of gut microbes and gut to systemic signaling. This would have far-reaching positive consequences to the field," Jain said.
An internationally recognized expert, Jain has received several national and international accolades for his work. Jain was recently awarded the international Stanley J. Dudrick Award and the Harry M. Vars award from the American Society for Parenteral and Enteral Nutrition as well as the Gerard Odell Prize for Excellence in Liver by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.
This prestigious NIH grant builds on previous research Jain has conducted for more than a decade and a half.
Jain has also received highly competitive funding from the National Institutes of Allergy and Infectious Diseases, National Institutes of Diabetes and Digestive and Kidney Diseases, the North American Society for Pediatric Gastroenterology Hepatology and Nutrition; the American Society of Parenteral and Enteral Nutrition Rhoads Research Foundation; the American Liver Foundation; Mid-America Transplant Foundation and industry partners. Additionally, seed funding through SLU's Liver Center and President's Research Fund allowed Jain to conduct early proof-of-concept studies.
Jain is the director of the M.D./Ph.D. program for SLU's School of Medicine. A SLUCare pediatric hepatologist and gastroenterologist, he serves as the associate division chief of pediatric gastroenterology, and the medical director of the pediatric liver transplant program at SSM Health Cardinal Glennon Children's Hospital.