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
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
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
"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
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.
in extramural funding
increase in funding from FY2014