Western diet promotes intratumor bacteria colonization and advances pancreatic Ductal adenocarcinoma
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Introduction Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with extremely poor prognosis and resistance to therapy. The presence of intratumor microbes in PDAC were thought to promote tumor growth and contribute drug resistance through bacterial dysbiosis; bacteria-derived products exert function in advancing tumor growth and inducing immune suppression. Diet is an important factor that influences dysbiosis of the gut microbiota, which induces resident of specific bacteria in tumors. In this study, we propose to define tumor-resident microbiome in mice fed with choline-low high fat high sugar diet (CL-HFS) and relationship of tumor-resident bacteria with intrapancreatic immunity. Methods C57BL/6 mice received either normal or CL-HFS diet for 14 weeks, followed by intra-pancreas inoculation of pancreatic cancer cells. 2 weeks later, mice were euthanized, buccal swab, tumors, and spleen were harvested. Tumors were digested into single cells and cultured on blood agar. Mixed bacteria colonies were sequenced for identification. Results HFS promotes tumor growth, worsens OS independent of weight loss, and facilitates the migration of 8 unique bacteria genera from the oral microbiome into the PDAC tumor. Splenomegaly, splenic melanosis, and reduction of T cells and macrophages population in melanotic spleens were the observed splenic complications. Conclusion Taken together, our result showed that HFS can advance orthotopically induced pancreatic cancer and facilitate bacteria colonization of the tumor. The long-term goal of the current study is to provide a comprehensive overview of the role of diet on the structure and function of intratumor microbiota; and to improve treatment strategies for PDAC patients.
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