Published online Nov 21, 2022. doi: 10.3748/wjg.v28.i43.6109
Peer-review started: July 12, 2022
First decision: September 26, 2022
Revised: October 4, 2022
Accepted: November 2, 2022
Article in press: November 2, 2022
Published online: November 21, 2022
The role of gut microbiota in ulcerative colitis (UC) cannot be ignored; however, most of current research is only based on the microbiota itself, ignoring microbiota metabolism. Microorganisms can reduce many biologically active substances, such as short-chain fatty acids, which have strong immuno-modulatory effects. Modern studies have reported that the destruction of the integrity of the mucus barrier is an early pathological change in UC. Different gut microbiota and their metabolites can influence the intestinal mucus barrier through different pathways, including altering epithelial structure, affecting mucin synthesis, secretion and degradation, and modulating immune responses.
At present, although many studies have confirmed the important role of gut microbiota in UC, the intricate relationship between microbiota and metabolites in UC has not been fully clarified. Association analysis of differential flora and their metabolites are required. It is worthwhile to conduct this study based on the intestinal mucus barrier to further reveal the potential differential biomarkers of UC.
The aim of the present study was to reveal the differential gut microbiota and metabolites that affect mucus in UC pathogenesis. The regulatory effect provides new evidence and new ideas for UC diagnosis.
In the present study, based on the intestinal mucus barrier, taking the intestinal flora and metabolism as the breakthrough point, a combination of antibiotics was used to establish pseudo-aseptic mice, and the widely used dextran sodium sulfate was used to establish colitis mice. Disease severity, mucus-associated protein expression, bacterial 16s rDNA sequences, and non-targeted metabolomes of bacterial and bacterial colitis mice were examined. The tract microbiota and metabolites play potentially important roles in UC pathogenesis by affecting the mucus barrier.
This study found that: (1) The antibiotics combination can effectively remove the intestinal flora of mice, and reduce bacterial abundance, and α and β diversity, alter community structure, and successfully establish pseudo-aseptic mice; (2) Comparing the bacteria-bearing mice with the pseudo-aseptic mice, the bacteria-bearing mice had more severe colitis based on disease activity index, more severe intestinal mucosal damage, and more obvious intestinal mucus loss; (3) In the intestinal flora of colitis mice, Candidatus Stoquefichus, Anaerobiospirillum, Rikenellaceae RC9 gut group, Prevotellaceae Ga6A1 group, and Negativibacillus were significantly increased, while Candidatus Saccharimonas and Muribaculum were significantly decreased. The significantly up-regulated metabolites in the intestinal flora of colitis mice included 3-deoxyhexitol and ortho-phosphoserine, and the significantly down-regulated metabolites were galacturonic acid, etc.; and (4) Further enrichment analysis found that the above differential metabolites were mainly associated with amino acid and energy metabolism. Spearman correlation analysis found that 3-deoxyhexitol, o-phosphoserine, etc. were positively correlated with the occurrence and development of colitis, and galacturaldehyde was positively correlated with the occurrence and development of colitis. There was a significant positive correlation between galacturonic acid and lactulose and the reduction and colitis recovery.
Candidatus Stoquefichus, Anaerobiospirillum, Rikenellaceae RC9 gut group, Prevotellaceae Ga6A1 group, and Negativibacillus are potentially emerging flora that induce or aggravate colitis, and Candidatus Saccharimonas and Muribaculum are potentially emerging flora that prevent or alleviate colitis. 3-Deoxyhexitol and o-phosphoserine may cause or aggravate colitis, while galacturonic acid may play a beneficial role in colitis alleviation and recovery. The differential metabolites of the flora are mainly enriched in the synthesis-related pathways of the rich-PTS sequence of the mucin MUC2 domain. They can affect the composition and function of mucus by regulating the expression of mucin, and finally act on the mucus barrier to induce aggravation or reduce colitis prevention.
This study identified some less-reported differential gut microbiota and their metabolites in colitis, which could affect UC progression by modulating mucin synthesis, altering mucus status and the mucus barrier. In future studies, we will carry out in-depth transplantation experiments of fecal bacteria and metabolites to further verify the experimental conclusions of this study.