Saccharomyces boulardii alleviates ulcerative colitis carcinogenesis in mice by reducing TNF-α and IL-6 levels and functions and by rebalancing intestinal microbiota

被引:153
作者
Wang, Chunsaier [1 ]
Li, Wenbin [1 ]
Wang, Hongying [2 ]
Ma, Yiming [2 ]
Zhao, Xinhua [2 ]
Zhang, Xudong [3 ]
Yang, Hong [1 ]
Qian, Jiaming [1 ]
Li, Jingnan [1 ]
机构
[1] Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Gastroenterol, Beijing 100730, Peoples R China
[2] Chinese Acad Med Sci & Peking Union Med Coll, Canc Hosp, Natl Canc Ctr, Beijing 100021, Peoples R China
[3] Univ Newcastle, Sch Biomed Sci & Pharm, New Lambton Hts, NSW, Australia
基金
中国国家自然科学基金;
关键词
Ulcerative colitis carcinogenesis; TNF-alpha; IL-6; Saccharomyces boulardii; Intestinal microbiota; INFLAMMATORY-BOWEL-DISEASE; MANAGEMENT; CANCER; MODULATION; DIAGNOSIS; PATHWAY; PATIENT; CELLS;
D O I
10.1186/s12866-019-1610-8
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Background and Aims To explore the inhibition mechanism of Saccharomyces boulardii (S. boulardii) on ulcerative colitis (UC) carcinogenesis. Methods C57BL/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 x 10(7) 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-alpha and IL-6 in colon tissue were measured by enzyme-linked immunosorbent assays. The influence of S. boulardii on TNF-alpha 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. Results S. boulardii treatment reduced AOM/DSS-induced UC carcinogenesis in mice, as indicated by the reduced tumor load and reduced TNF-alpha and IL-6 levels in vivo, as well its effects on TNF-alpha 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. Conclusions S. boulardii effectively reduced UC carcinogenesis in an AOM/DSS induced mice model. This positive result can likely be attributed to the reduction of TNF-alpha and IL-6 levels or the blockade of their function combined with alterations to the intestinal microbiota.
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页数:12
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