# Regulation of amino acid absorption in the mammalian small intestine

> **NIH NIH R01** · MARSHALL UNIVERSITY · 2020 · $478,132

## Abstract

The amino acid glutamine is the primary nutrient for the intestinal enterocytes
and thus, critical for the health of the epithelium. However, how glutamine is assimilated
in the normal mammalian small intestine and/or in a primarily mucosal disease such as
inflammatory bowel disease (IBD) is not well known. Glutamine is absorbed via Na-
glutamine co-transport (NGcT) on the brush border membrane (BBM) of enterocytes.
We have demonstrated that B0AT1 mediates NGcT on the BBM of villus cells. And in
paradigm shift, we demonstrated the only nutrient absorptive process on the BBM of
crypt cells, specifically SN2, which mediates NGcT in these cells. Further, in a rabbit
model of chronic intestinal inflammation resembling IBD we demonstrated that NGcT in
total was reduced. This net inhibition was a sum of B0AT1 inhibition in villus cells and
SN2 stimulation in crypt cells. The mechanism of inhibition of B0AT1 was secondary to a
reduction in the number of co-transporters in the villus cell BBM while the mechanism of
stimulation of SN2 in crypt cells was secondary to an increase in the affinity for
glutamine. Thus, glutamine assimilation which occurs via distinct transporters in villus
and crypt cells is uniquely regulated in the chronically inflamed intestine. Importantly,
similar results were seen in the human IBD intestine. Additional preliminary studies
indicated that immune inflammatory mediators known to be produced in the chronically
inflamed intestine may be responsible for these unique alterations in glutamine
absorption. Given this background, the overall aim is to determine the immune
mechanism of regulation of B0AT1 in villus and SN2 in crypt cells in the chronically
inflamed intestine. Better understanding of the regulation of glutamine absorption in the
normal and IBD intestine will provide the foundation to develop more efficacious, specific
immune based nutritional therapies for IBD.

## Key facts

- **NIH application ID:** 10001495
- **Project number:** 5R01DK108054-05
- **Recipient organization:** MARSHALL UNIVERSITY
- **Principal Investigator:** Uma Sundaram
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $478,132
- **Award type:** 5
- **Project period:** 2016-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001495

## Citation

> US National Institutes of Health, RePORTER application 10001495, Regulation of amino acid absorption in the mammalian small intestine (5R01DK108054-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001495. Licensed CC0.

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