# Project 3 - Ming Song

> **NIH NIH P20** · UNIVERSITY OF LOUISVILLE · 2021 · $218,400

## Abstract

Project Title: Metabolic effect of fructose in intestine induces gut microbiota dysbiosis
Abstract. Emerging evidence has demonstrated that gut microbiota dysbiosis plays a causative role in the
development of obesity, type 2 diabetes and NAFLD. Gut “physiologic hypoxia” is key to maintaining a balanced
gut microbiota and gut barrier function. Disturbance of gut “physiologic hypoxia”, namely oxygenation, results in
gut microbiota dysbiosis. Our preliminary studies have shown that chronic feeding with either fructose or glucose
induces gut microbiota dysbiosis in a similar manner in rats and mice. Moreover, both daily gavage and chronic
feeding with fructose or glucose results in intestinal oxygenation as shown by HIF-1 alpha reporter (ODD-luc)
mice, and this effect is more robust with glucose. Given that fructose is preferentially metabolized under hypoxia,
and glucose can be rapidly converted to fructose via the polyol pathway, the proposed studies will test the
hypothesis that fructose metabolism in the intestine results in metabolic reprogramming which switches the host
metabolic pathway from mitochondrial β-oxidation to glycolysis and consumes less oxygen. This, in turn, leads
to intestinal oxygenation, subsequent inhibiting the growth of obligate anaerobic bacteria and facilitating the
expansion of pathogenic bacteria. The hypothesis will be tested in three specific aims: Aim 1. Determine
whether fructose induces metabolic reprogramming in intestinal epithelial cells and determine if this results in
gut microbiota dysbiosis. We will test the hypothesis that fructose metabolism in the intestine results in metabolic
reprogramming and leads to intestinal oxygenation, which in turn, results in gut microbiota dysbiosis. Aim 2.
Determine whether modulation of glycolytic activity in intestinal epithelial cells alters gut microbiota composition.
We hypothesize that genetic modulation of glycolytic activity via 6-phosphofructo-2-kinase/fructose-2,6-
bisphosphatase (PFK2) in intestinal epithelial cells results in altered oxygen consumption rate which in turn leads
to the alteration of gut microbiota. Aim 3. Determine whether the metabolic effect of fructose in intestine
contributes to the development of NAFLD. We will test the hypothesis that the metabolic effects of fructose in
intestine on the development of NAFLD is mediated by gut microbiota dysbiosis.

## Key facts

- **NIH application ID:** 10026257
- **Project number:** 2P20GM113226-06
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Ming Song
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $218,400
- **Award type:** 2
- **Project period:** 2016-06-10 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10026257

## Citation

> US National Institutes of Health, RePORTER application 10026257, Project 3 - Ming Song (2P20GM113226-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10026257. Licensed CC0.

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