# Role of the bile acid activated receptors FXR and TGR5 in Total Parenteral Nutrition associated hepatic and gut disease

> **NIH NIH K08** · SAINT LOUIS UNIVERSITY · 2021 · $71,820

## Abstract

PROJECT SUMMARY / ABSTRACT
Total Parenteral nutrition (TPN) provides nutrition by bypassing the gut. It is a crucial lifesaving therapy for over
30,000 individuals in the US permanently dependent on TPN. Several fold higher numbers of patients require
TPN for a prolonged duration. It is also used worldwide. Unfortunately, its use causes potentially fatal liver and
gut injury from a likely multifactorial, yet unknown etiology. No established ameliorative strategies exist.
 Dr. Jain’s long-term career goal is to become an independent NIH-funded physician scientist in the
niche field to develop strategies to ameliorate TPN associated pathology. His focus is on understanding the
interplay of bile acid regulated pathways that modulate the Gut-Liver axis during TPN infusion. The objective
of the K08 proposal was to obtain training in designing hypothesis driven proposals, acquiring research
techniques, performing experiments, critically analyzing data and developing skills to overcome pitfalls. He has
obtained very encouraging data resulting in many manuscripts and several national awards, helping advance
his academic pursuits. Indeed, with this award he has also been generating a critical mass of data and
publications to apply for an NIH R01 grant, however, his trajectory was interrupted due a halt in studies for
almost 12 months, per University policies and guidelines, in response to COVID-19 during most of 2020 and
the beginning of 2021. The university has now, in 2021 allowed the studies to continue.
 As detailed in his research plan; with Aim 1 he evaluated gut and hepatic outcomes in TPN infused
animals given Farnesoid X Receptor (FXR) agonists and will further assess impact from FXR regulated
downstream protein FGF19 to determine additional mechanistic links. Aim 2 relates to exploring the
mechanisms by which the TGR5-GLP axis additionally regulates TPN pathology. He has tested responses to
intravenously infused Glucagon Like Peptide-2 (GLP-2) and enterally administered TGR5 agonist and will
further assess GLP-1 in animals receiving TPN. Aim 3 addresses alteration in gut microbiota, specifically a
clonal Bacteroidetes proliferation leading to impaired gut integrity and thus endotoxin and cytokine mediated
injury in animals on TPN. Each of his aims have used several highly novel strategies. These aims have
supported Dr. Jain’s career development by providing training in mechanistic aspects of TPN pathobiology as
related to the roles of bile acid regulated pathways.
 Finally, Dr. Jain continues to have a research environment in a preeminent academic research
institution (Saint Louis University) with leaders in the field at the SLU Liver center, a designated center of
excellence. Most importantly, Dr. Jain is a candidate who has shown extreme determination to advance his
research and has full institutional commitment to enable him to succeed.

## Key facts

- **NIH application ID:** 10390680
- **Project number:** 3K08DK098623-05S1
- **Recipient organization:** SAINT LOUIS UNIVERSITY
- **Principal Investigator:** Ajay K. Jain
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $71,820
- **Award type:** 3
- **Project period:** 2016-02-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390680

## Citation

> US National Institutes of Health, RePORTER application 10390680, Role of the bile acid activated receptors FXR and TGR5 in Total Parenteral Nutrition associated hepatic and gut disease (3K08DK098623-05S1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10390680. Licensed CC0.

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