# Regulation of Intestinal Butyrate Transporters by Oxidative and Inflammatory Status

## TL;DR

This paper explores how oxidative stress and inflammation affect butyrate transporters in the colon, which are important for preventing diseases like colorectal cancer and inflammatory bowel disease.

## Contribution

The paper highlights the potential role of Nrf2, TNF-α, and IFN-γ in modulating butyrate transporters under oxidative and inflammatory conditions.

## Key findings

- Oxidative stress and inflammation may modulate butyrate transporters like MCT1, SMCT1, BCRP, and MCT4.
- Nrf2, TNF-α, and IFN-γ are suggested to mediate the effects of oxidative stress and inflammation on these transporters.
- More research is needed to establish these transporters as potential targets for treating intestinal diseases.

## Abstract

Beneficial effects of the microbiota-derived metabolite butyrate at the colonic level are well established, particularly through its relevance in colorectal cancer (CRC) and inflammatory bowel disease (IBD), two major intestinal pathologies. Therefore, the mechanisms involved in butyrate transport across colonic epithelial cell membranes (uptake transporters: monocarboxylate transporter 1 (MCT1) and sodium-coupled monocarboxylate transporter 1 (SMCT1); efflux transporters: breast cancer resistance protein (BCRP) and MCT1/monocarboxylate transporter 4 (MCT4)), which are determinant for its intracellular levels, are of primary importance for its beneficial effects at the colonic level. The available data suggest that all these butyrate transporters can be modulated by redox and inflammatory status, but the evidence is scarce and rather inconsistent. Nevertheless, a role of nuclear factor erythroid 2-related factor 2 (Nrf2) and of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mediating the effect of oxidative stress and inflammation, respectively, on MCT1 and SMCT1 is suggested. So, more investigation on this subject is needed, given the fact that increased oxidative stress levels and inflammatory status are present in a series of intestinal conditions and pathologies, including CRC and IBD, which could help to establish these transporters as potential cellular targets in these diseases.