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
Processing time: 127 Days and 2.3 Hours
Intestinal micro-ecological imbalances impair the intestinal barrier and induce intestinal inflammation, for example, ulcerative colitis (UC). According to the latest research, abnormalities in intestinal microbiota structure and their metabolites play a dominant role in UC progression; in addition, they could affect the mucus barrier based on different factors. Although numerous studies have confirmed the important role of intestinal microbiota in UC pathogenesis, the intricate connection between microbiota and metabolites and mucus barrier in UC occurrence remains unclear, and correlation analyses of differential microbiota and their metabolites under UC are relatively scarce.
To reveal the differential intestinal microbiota and metabolites in UC path
We used the antibiotic combination method to establish intestinal pseudo-aseptic mice; afterward, dextran sulfate sodium (DSS) was applied to establish an acute experimental colitis mice model. Colitis severity, assessed based on disease activity index, colorectal length, colorectal wet weight, and histological lesions, and mucus-related staining (mucopolysaccharide alcian blue and immunofluorescence of mucin), was compared between the pseudo-aseptic and bacterial colitis mice. Finally, differential intestinal microbiota, metabolites, and their association and correlations, were analyzed by 16s rDNA sequencing in combination with non-targeted metabolomics, through gas chromatography-mass spectrometry.
Compared with the pseudo-aseptic mice, intestinal bacteria positive mice were more severely ill and their intestinal mucus loss was more pronounced in DSS-induced colitis (P < 0.05), suggesting that different microbiota and metabolites could cause the different degrees of colitis. Subsequently, we observed that in addition to Klebsiella, and Bacteroides, which were widely associated with colitis, Candidatus Stoquefichus, Anaerobiospirillum, Muribaculum, and Negativibacillus may be involved in protection against colitis. Furthermore, differential metabolites of the microbiota were mainly enriched in the synthesis-related pathways of key structural sequences of mucin. In combination with the mucin-related staining and immunofluorescence results, the findings indicate that the differential microbiota and their metabolites potentially regulate the composition and function of mucus under colitis.
Microbiota and their metabolites are major factors regulating the composition and function of mucus, in turn influencing the function and structure of intestinal mucus barrier under colitis. The different microbiota and metabolites identified in the present study could be novel biomarkers for colitis.
Core Tip: We observed that the differences in microbiota and their metabolites can cause different degrees of colitis. The differential metabolites of the microbiota in colitis are mainly enriched in pathways related to the key structural sequence synthesis of mucin, and the different levels of the metabolites lead to differential expression of mucin and mucus. Therefore, the differential metabolites of colitis could regulate the composition and function of mucus. In addition, the differential intestinal microbiota and their metabolites in mice with colitis were largely associated with amino acid and energy metabolism.