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Streptococcus gallolyticus conspires myeloid cells to promote tumorigenesis of inflammatory bowel disease

Zhang, Yucheng, Weng, Yijie, Gan, Huoye, Zhao, Xinmei, Zhi, Fachao
Biochemical and biophysical research communications 2018 v.506 no.4 pp. 907-911
Streptococcus gallolyticus, adenoma, azoxymethane, carcinogenesis, carcinoma, chemokine CCL2, colitis, colorectal neoplasms, dendritic cells, dextran, interleukin-1beta, interleukin-6, interleukin-8, macrophages, mast cells, metagenomics, mice, ribosomal RNA, sequence analysis, sodium sulfate, suppressor cells, tumor necrosis factor-alpha
Metagenomic analyses indicate that streptococcus gallolyticus is enriched at carcinoma in colitis associated colorectal cancer compared with sporadic colorectal cancer. But the particular mechanism of streptococcus gallolyticus in Inflammatory Bowel Disease malignant progression remains undefined yet. We aim to explore the biological carcinogenesis efficacy of streptococcus gallolyticus and its potential mechanism in azoxymethane and dextran sodium sulphate-induced colitis associated colorectal cancer in mice. Oral pretreatment of streptococcus gallolyticus was adopted to evaluate its detrimental effect. The colorectums of experimental C57BL/6 mice were collected and examined for the degree of tumorigenesis. Comparative 16S rRNA sequencing was carried out to observe streptococcus gallolyticus alterations in abundance. We found that streptococcus gallolyticus are enriched in colonic carcinoma compared to adenoma and healthy mice. Pretreatment of Streptococcus gallolyticus aggravated tumor formation, with more colonic obstruction, larger number and diameter of tumor node. Furthermore, Streptococcus gallolyticus selectively recruits tumor-infiltrating myeloid cells but not mast cells, including marrow-derived suppressor cells, tumor-associated macrophages and dendritic cells, which can inhibit competence of T cells. Moreover, several myeloid-cell-derived proinflammatory cytokines (IL-6, IL-1β, IL-8, CCL2, COX-2, TNF-α) were increased with the formation of carcinoma in IBD. Collectively, these data suggest that, through recruitment of tumor-infiltrating immune cells, Streptococcus gallolyticus generate an immune suppressive microenvironment that is conducive for neoplasia progression of Inflammatory Bowel Disease.