# Inhibitory effects and amino acid metabolism regulations of active polyphenol from foxtail millet bran on chronic colitis in mice

## TL;DR

A polyphenol extract from foxtail millet bran reduces chronic colitis in mice by regulating inflammation and amino acid metabolism.

## Contribution

The study identifies low-molecular-weight polyphenols from millet bran as effective in alleviating chronic colitis through amino acid metabolism modulation.

## Key findings

- BPLP reduced pro-inflammatory cytokines and improved gut barrier integrity in DSS-induced colitis.
- BPLP modulated amino acid metabolism pathways like valine/leucine/isoleucine and phenylalanine/tyrosine/tryptophan biosynthesis.
- Specific amino acid changes in BPLP-treated mice matched those seen in human IBD patients.

## Abstract

Inflammatory bowel disease (IBD) is frequently associated with metabolic imbalances. Polyphenols have demonstrated efficacy in alleviating colitis by restoring the metabolic disorders. Our previous studies revealed that bound polyphenols extracted from millet bran could alleviate acute colitis and colitis-associated colorectal cancer (CRC) via restoring the gut microbiome and that the low molecular weight (MW) (<200 Da) portion of bound polyphenol (BPLP) constituted the primary active component, comprising six phenolic acids.

To further evaluate the effects of BPLP on inflammation, a dextran sodium sulfateb(DSS)-induced experimental colitis model was constructed, and BPLP was gavaged on mice. The effects of BPLP on colitis were assessed by detecting the weight, mouse status, gut barrier integrity, and inflammatory cytokine secretion. Additionally, non-targeted metabolomics was used to identify altered metabolites.

BPLP administration restored body weight and colon length, protected epithelial structure from DSS-induced damage, and relieved chronic colitis. In colons, BPLP reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), enhanced the secretion of the anti-inflammatory cytokine IL-10, and upregulated the expression of tight junction proteins. Nontarget metabolomic results showed that BPLP alleviated colitis by modulating amino acid metabolism pathways, including valine/leucine/isoleucine biosynthesis,phenylalanine/tyrosine/tryptophan biosynthesis, and phenylalanine metabolism. Furthermore, alterations in specific amino acids, such as valine and beta-alanine, were consistent with profiles observed in clinical IBD patients. Collectively, these results indicate that BPLP effectively alleviates chronic colitis in mice and regulates inflammation-related amino acid metabolism in vivo.

Diagram illustrating the effects of foxtail millet bran-derived BPLP on colitis in mice. DSS-induced colitis is shown in the upper section. Bran is processed into BPIS and BPLP, indicated to improve gut health. The lower section depicts reduced colitis symptoms and inflammation markers (TNF-alpha, IL-1beta, IL-6), with increased metabolites (phenylpyruvic acid, leucine, tyrosine, cysteine) associated with treatment.