# Effect of dysbiotic gut microbiota on the transport of short-chain fatty acids: Relevance to autoimmune disorders

> **NIH NIH R21** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $431,750

## Abstract

Summary
Short-chain fatty acids (SCFAs) are metabolites produced by the fermentation of fibers by bacteria in the gut
and play an important role in the maintenance of health and disease prevention in a variety of disorders,
including metabolic, autoimmune, and neurological diseases. The sufficient production of SCFAs in the gut and
their efficient absorption by intestinal epithelial cells and transport into systemic circulation are important for
disease prevention. Although the effect of prebiotics and probiotics on the production of SCFAs in the gut has
been extensively studied, their effect on the absorption and transport of SCFAs has not been well studied.
Low-grade intestinal inflammation is one of the causes of reduction in the expression of SCFAs-transporter
genes and the transport of SCFAs into the systemic circulation. We found that the levels of intestinal
inflammation biomarker are increased in MS patients compared to healthy donors (HDs), and the levels of the
SCFA acetate are lower in the blood but higher in fecal samples in MS patients compared to HDs, suggesting
insufficient absorption and transport of SCFA acetate in MS patients. We hypothesize that MS-associated gut
dysbiosis may trigger and/or exacerbate the inflammation in the gut and subsequently reduce the expression of
SCFAs-transporter genes and their transport into the system circulation. To examine this hypothesis, germfree
mice will be transplanted with fecal samples collected from MS patients and HDs, and examined for the
expression of SCFA-transporters and tight junction proteins, intestinal permeability, and concentration of SCFAs
in fecal and blood samples. Further, we will examine the development of experimental autoimmune
encephalomyelitis (EAE), an animal model of MS, in the human microbiota-transplanted mice in Aim-1.
We found that the abundance of B. massiliensis was significantly associated with increased levels of acetate,
butyrate, and propionate in the blood. B. massiliensis is a newly isolated bacterium from healthy human fecal
samples, and its effect on health has not been explored yet. Of interest, the culture supernatant of B.
massiliensis and its outer membrane vesicles (OMVs) up-regulated the expression of SCFAs-transporter genes.
We also found that A. hallii, SCFA-producing bacterium, is reduced in the gut of MS patients and that intake of
high-fiber diets (HFD) can increase the colonization of SCFAs-producing bacteria. Therefore, we hypothesize that
treatment with A. hallii or HFD can increase the production of SCFAs in the gut and increased colonization of B.
massiliensis could promote the transport of SCFAs into the blood circulation. We will test this hypothesis in Aim-2.
In this study, we will elucidate a novel mechanism of how the gut microbiome impacts health and modulates
disease, and identify a synbiotic intervention with HFD and B. massiliensis as a beneficial treatment for
autoimmune diseases including MS.

## Key facts

- **NIH application ID:** 11055822
- **Project number:** 1R21AT012804-01A1
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** SUHAYL S. DHIB-JALBUT
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $431,750
- **Award type:** 1
- **Project period:** 2024-09-16 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11055822

## Citation

> US National Institutes of Health, RePORTER application 11055822, Effect of dysbiotic gut microbiota on the transport of short-chain fatty acids: Relevance to autoimmune disorders (1R21AT012804-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11055822. Licensed CC0.

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