SLU Hepatologist Awarded NIH Grant to Study Liver, Gut Disorders

A lifesaving therapy for premature babies and people with injuries that prevent them from eating can cause severe liver failure and gut atrophy. A Saint Louis University researcher is studying how to prevent the damage from parenteral nutrition (PN), more commonly known as intravenous feeding.

Ajay Jain, M.D., a SLUCare pediatric hepatologist and gastroenterologist and the medical director of the pediatric liver transplant program at SSM Health Cardinal Glennon Children's Hospital, received a $703,620 grant from the National Institutes of Diabetes and Digestive and Kidney Diseases to continue studying strategies for PN-associated disorders.

The funds will further his work into the role of bile acid activated receptors FXR and TGR5 in PN-associated hepatic and gut disease. The grant also provides support for research into gut microbes.

The NIH grant builds on previous research. Jain, an assistant professor of pediatrics at Saint Louis University, received a $150,000 grant from the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN) in 2015 and a $50,000 grant from the American Society of Parenteral and Enteral Nutrition (ASPEN) Rhoads Research Foundation in 2014.

People receive PN when part, or all, of their digestive system doesn't function normally. A solution containing carbohydrates, proteins, lipids, vitamins, minerals and other nutrients essential for normal nutrition is given intravenously.

It is a common and critical therapy for sick babies, children and adults all around the world. Despite being a life saver, PN causes several complications, Jain said, including a life threatening and potentially fatal liver and bowel disease - especially in fragile NICU babies.

The cause of the liver and bowel disease is unknown, Jain said, but is likely caused by several factors. No established therapies exist to prevent the onset of the liver and bowel disease.

Jain's research focuses on understanding the interplay of bile acid regulated pathways that modulate the gut-liver axis during PN infusion. He says the way the gut and liver communicate to maintain normal health is disrupted while a patient receives intravenous nutrition.

In a clinical setting, Jain has found mitigation of PN-associated side effects if at least some nutrition can be provided via the gut.

"It almost appears as if some food delivery to the gut is of paramount importance to generate critical signals to maintain normal health and prevent such injury" Jain said.

It almost appears as if some food delivery to the gut is of paramount importance to generate critical signals to maintain normal health and prevent such injury

Jain's research also will assess the role of the gut microbiome during parenteral nutrition.

"There are about a 100 trillion bacteria in the gut. In fact, microbial genome exceeds the human genome by almost a 100 fold, making us genetically 99 percent bacteria and 1 percent human," Jain said. "PN may change the finely regulated gut microbiome. Our measures are aimed at restoring the normal gut-liver cross talk and the gut microbiome to as close to normal again as possible."

Jain said his previous work on PN, funded through competitive SLU grants (Presidents Research Fund, Fleur-de-Lis grant, Liver Center grant) and foundation grants including the American Liver Foundation award, has yielded encouraging new data. With the NIH funding, Jain aims to:

• Critically evaluate gut and hepatic injury during PN therapy;
• Explore the mechanisms that regulate PN pathology; and
• Address alteration in gut microbiota.

Jain's work has identified unique molecules and pathways that are altered during PN. In this project, he will assess these molecules and devise strategies and pharmacological therapies to correct the defect and mitigate complications.

Such research could help bring a paradigm change to current preventative strategies.

"It would be the biggest reward if we can ultimately devise interventions to help PN-associated injuries which unfortunately maximally affect our most vulnerable and most precious population segment - the babies," Jain said.

Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award number 1K08DK098623-01A1.

The Saint Louis University Liver Center enjoys worldwide recognition as a center of excellence for research and treatment of liver diseases and liver cancer.

Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: infectious disease, liver disease, cancer, heart/lung disease, and aging and brain disorders.