Background and AimsTo explore the inhibition mechanism of Saccharomyces boulardii (S. boulardii) on ulcerative colitis (UC) carcinogenesis.MethodsC57BL/6 mice were treated with azoxymethane and dextran sulfate sodium (AOM/DSS) to develop a UC carcinogenesis model. The treatment group was lavaged with S. boulardii (5 × 107 CFU/d) for 12 weeks. The mice were sacrificed and the tumor load in the treatment group was compared with that of a control group. The levels of TNF-α and IL-6 in colon tissue were measured by enzyme-linked immunosorbent assays. The influence of S. boulardii on TNF-α and IL-6 regulation was also investigated using different colon cell lines. Differences in intestinal microbiota in both stool and intestinal mucosa samples were assessed using 16S rDNA sequencing.ResultsS. boulardii treatment reduced AOM/DSS-induced UC carcinogenesis in mice, as indicated by the reduced tumor load and reduced TNF-α and IL-6 levels in vivo, as well its effects on TNF-α and IL-6 activities in vitro. Significant changes in both fecal and mucosal microbiota were observed among the control, the AOM/DSS treated, and AOM/DSS plus S. boulardii treated groups. For fecal microbiota, the AOM/DSS treated group was lower in Lactobacillus, but higher in Oscillibacter and Lachnoclostridium than the control group. After intervention with S. boulardii, the percentage of Bacillus and Lactococcus increased, but Lachnoclostridium, Oscillibacter, Bacteroides, and Pseudomonas decreased. For the intestinal mucosal microbiota, the AOM/DSS treated group was lower in Bifidobacterium and Ruminococcaceae_UCG-014 and higher in Alloprevotella than the control group. After S. boulardii exposure, the percentage contributions of Lachnoclostridium and Lachnospiraceae_NK4A136 increased.ConclusionsS. boulardii effectively reduced UC carcinogenesis in an AOM/DSS induced mice model. This positive result can likely be attributed to the reduction of TNF-α and IL-6 levels or the blockade of their function combined with alterations to the intestinal microbiota.
Background: Pancreatic cancer is one of the most lethal cancers worldwide. No effective screening methods exist, and available treatment modalities do not effectively treat the disease. Established risk factors for pancreatic cancer, including smoking, chronic pancreatitis, obesity and type 2 diabetes mellitus, collectively account for less than half of all pancreatic cancer cases. Accumulating reports have demonstrated that there is an association between pathogenic microorganisms and pancreatic cancer. Summary: A substantial amount of preclinical and clinical evidence suggests that microbiota are likely to influence pancreatic carcinogenesis. This review summarizes the literature on studies examining infections that have been linked to pancreatic cancer. Key Message:Helicobacter pylori infection may be a risk factor for pancreatic cancer; chronic hepatitis virus and oral microbiota may also play a role in pancreatic carcinogenesis. Practical Implications: Considering the worldwide burden of the disease, the association between microbiota and pancreatic cancer in this review may provide new ideas to prevent and treat pancreatic cancer more efficiently. Further studies in this direction are urgently needed.
The downregulation of farnesoid X receptor (FXR; gene name, nuclear receptor subfamily 1 group h member 4), an enteric nuclear bile acid receptor, has been reported in colorectal carcinoma (CRC), and FXR expression has been inversely correlated with CRC stage and clinical outcome. FXR knockdown in chronic colitis mouse models of intestinal tumorigenesis results in early mortality and increased tumor progression via promoting Wnt signaling. The aim of the present study was to explore the effects and mechanism of FXR on the Wnt/β-catenin signal pathway in CRC. FXR and β-catenin protein expression levels were detected in an ulcerative colitis mouse model and human colon cancer cell lines (HT-29, Caco-2 and HCT-116). Gain-and loss-of-function studies were conducted by transfecting colon cancer cells with FXR siRNA and treating them with the FXR agonist GW4064. Subsequently, β-catenin transcriptional activity was measured using the dual-luciferase assay, and β-catenin/TCF4 complex levels and β-catenin protein and mRNA expression levels were determined. FXR and β-catenin expression levels were inversely associated in both the animal model and colon cancer cells. The Wnt signaling pathway was activated by increased β-catenin/TCF4 complex levels upon FXR silencing; however, mRNA and protein levels of β-catenin were not significantly affected. The FXR agonist GW4064 significantly inhibited the proliferation of cells but promoted the transcriptional activity of β-catenin. Thus, the present study demonstrated that FXR influences the Wnt/β-catenin signaling pathway. Furthermore, loss of FXR expression promotes the transcriptional activity of β-catenin, whereas FXR activation results in the opposite effect.
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