Analysis of Intestinal Microflora and Metabolites From Mice With DSS-Induced IBD Treated With Schistosoma Soluble Egg Antigen

Abstract

Objective: This study aimed to analyze the changes in intestinal flora and metabolites in the intestinal contents of mice with inflammatory bowel disease (IBD) to preliminarily clarify the mechanism of action of Schistosoma soluble egg antigen (SEA) on IBD, thus, laying a research foundation for the subsequent treatment of IBD.Methods: A total of 40 Institute of Cancer Research (ICR) mice were divided into four groups: control, SEA 50 μg, dextran sulfate sodium salt (DSS), and SEA 50 μg + DSS. The overall state of the animals was observed continuously during modeling. The colonic length was measured after 10 days of modeling. The degree of colonic inflammation was observed by hematoxylin and eosin staining. 16srRNA and liquid chromatography–mass spectrometry sequencing techniques were used to determine the abundance of bacteria and metabolites in the intestinal contents of mice in the DSS and SEA 50 μg + DSS groups, and the differences were further analyzed.Results: After SEA intervention, the disease activity index score of mice with IBD decreased and the colon shortening was reduced. Microscopically, the lymphocyte aggregation, glandular atrophy, goblet cell disappearance, and colonic inflammation were less in the SEA 50 μg + DSS group than in the DSS group (p < 0.0001). After SEA intervention, the abundance of beneficial bacteria prevotellaceae_UCG-001 was upregulated, while the abundance of the harmful bacteria Helicobacter, Lachnoclostridium, and Enterococcus was downregulated in the intestinal tract of mice with IBD. The intestinal metabolite analysis showed that SEA intervention decreased the intestinal contents of glycerophospholipids (lysophosphatidylcholine, lysophosphatidylethanolamine, phatidylcholine, and phatidylethanolamine) and carboxylic acids (L-alloisoleucine and L-glutamate), whereas increased bile acids and their derivatives (3B,7A,12a-trihydroxy-5A-cholanoic acid and 3A,4B, 12a-trihydroxy-5b-cholanoic acid). Combined microbiota–metabolite analysis revealed a correlation between these differential microbiota and differential metabolites. At the same time, the changes in the contents of metabolites and differential metabolites in the two groups also correlated with the abundance of the gut microbiome.Conclusions: The study showed that SEA reduced DSS-induced inflammation in IBD and improved the symptoms of IBD in mice through the combined regulation of intestinal flora and intestinal metabolism. It suggested a potential possibility for the use of SEA in treating and regulating intestinal flora and metabolism in patients with IBD.

Potential Gut Microbiota Features for Non-Invasive Detection of Schistosomiasis

“…Liver injuries and alterations of gut microbiota are associated with the infection of schistosomes and other pathogenic or non-pathogenic factors. These factors, such as S. japonicum ( 20 , 29 , 44 ), S. mansoni ( 19 , 21 , 22 ), Clonorchis sinensis ( 45 ), HBV ( 46 , 47 ), hepatitis C virus (HCV) ( 48 ), Tetrachloromethane (CCl4) ( 49 ) and alcohol ( 50 ), induce the dysbiosis of the gut microbiota of animals and humans and acute or chronic liver injuries such as advanced schistosomiasis, liver cirrhosis and liver cancer. Our study found significant differences in the gut microbiota of mice and humans infected with S. japonicum , and S. japonicum infection showed a decrease in gut microbial diversity of hosts and an increase in the relative abundance of the genera Bacteroides , Blautia and Lactobacillus .…”

“…In addition, Blastocystis infection induced the decrease of Bacteroides in children ( 51 ). The abundance of genus Enterococcus was significantly downregulated in the intestinal tract of mice with inflammatory bowel disease (IBD) after Schistosoma soluble egg antigen (SEA) intervention ( 44 ) and was associated with the progression of the HBV related acute-on-chronic liver failure ( 52 ). Phyla Firmicutes and Bacteroidetes represent more than 50% of the total bacterial composition in mice infected with Schistosoma mansoni ( 19 ), which was similar to our findings, However, there is no significant difference in the relative abundance of genera Bacteroides , Blautia and Lactobacillus after Schistosoma mansoni infection.…”

Cysteine protease of Clonorchis sinensis alleviates DSS-induced colitis in mice

“…Recent studies have reported that 50 μg of helminth-derived protein is the usual dose for colitis treatment in mice [29][30][31][32]. There are also 20 μg and 100 μg per day or even lower or higher doses [13,31].…”

New insights into the interplay between intestinal flora and bile acids in inflammatory bowel disease

“…In the normal intestinal flora of mice, the distribution and abundance of bacteria in the intestinal epithelium after VDR knockout were significantly changed, mainly manifested as increased abundance of Bacteroides fragilis in mice with VDR deletion[ 82 ]. In addition, intestinal epithelial VDR deletion exacerbated the intestinal inflammatory damage caused by sodium glucan sulfate modeling in mice, while the intestinal epithelial VDR deletion mice and wild-type control mice were reared in the same cage for modeling, this difference in intestinal inflammation caused by different genotypes disappeared[ 83 ]. This indicates that VDR deficiency causes intestinal flora disorder and aggravates the occurrence and development of IBD.…”