# The Relationship Between Short-Chain Fatty Acid Secretion and Polymorphisms rs3894326 and rs778986 of the FUT3 Gene in Patients with Multiple Sclerosis—An Exploratory Analysis

## TL;DR

This study explores how genetic variations in the FUT3 gene relate to short-chain fatty acid levels in people with multiple sclerosis.

## Contribution

The study is the first to investigate the association between FUT3 gene polymorphisms and SCFA secretion in MS patients.

## Key findings

- No significant differences in FUT3 polymorphism prevalence were found between MS patients and healthy controls.
- A tendency for higher caproic acid in rs778986 heterozygotes and higher valeric acid in rs3894326 homozygotes was observed.
- The study suggests possible links between FUT3 polymorphisms and specific SCFA levels, though results require validation in larger cohorts.

## Abstract

Background: The intestinal microflora is a population of microorganisms that resides in the human gastrointestinal tract and is important in maintaining metabolic and immune homeostasis in the body. Bacteria residing in the intestine produce short-chain fatty acids (SCFAs), which communicate with, among other things, the brain–gut axis—disorders of which are one of the causes of MS-like pathologies. A particular property of SCFAs is the induction of regulatory T cells, which are finding their way into pioneering therapies for MS patients. The aim of the study is to evaluate SCFA secretion in patients with multiple sclerosis from the West Pomeranian region depending on the genotypes of rs778986 and rs3894326 polymorphisms of the FUT3 gene. Methods: The study group included 47 patients clinically diagnosed with MS. Genotyping was performed by real-time PCR using TaqMan probes. Analysis of short-chain fatty acids in faeces was performed on a quadrupole mass spectrometer coupled to a time-of-flight (QTOF) analyser coupled to an AB Sciex high-performance liquid chromatograph (UHPLC). Results: Statistical analysis did not reveal any statistically significant differences in the prevalence of the studied polymorphisms in MS patients compared to the healthy control group. It was observed that the intestinal microflora and SCFA production in MS patients may be disturbed, while the studied FUT3 gene polymorphisms probably do not have a significant effect on their concentrations. A statistical tendency towards higher caproic acid content in heterozygotes of the rs778986 polymorphism and higher valeric acid secretion in homozygotes of rs3894326 was demonstrated. Conclusions: In summary, the studied FUT3 gene polymorphisms are not overrepresented in patients with MS. The rs778986 FUT3 polymorphism may affect the caproic acid content in the faeces of patients with MS, and the rs3894326 polymorphism may affect valeric acid secretion. Due to the small sample size and sparse genotype groups, the study has limited power and negative findings may reflect Type II error; replication in larger cohorts is warranted.