Role of mouse microbiome in cancer and inflammation

在癌症免疫生物学部分，以及癌症和炎症项目的其他部分，以及CCR的其他部分，非常需要了解肠道菌群在炎症性和免疫性结肠炎发病机制中的作用，以及在结肠炎相关癌症的小鼠模型中的作用。我们广泛使用缺乏免疫或炎症相关基因的小鼠，总是很难区分这些基因对结肠炎或癌症的直接影响，还是通过调节肠道菌群的间接影响。本项目的其他合作研究是针对肝脏免疫反应在控制肝癌发生中的作用，肝脏的炎症免疫微环境也可能受到肠道菌群组成的显著影响。总的来说，这些研究将极大地受益于获得无菌设施，特别是通过基于最先进的测序和生物信息学的肠道微生物学专业知识的可用性，这些专业知识很难获得单个实验室，但可以有效地提供给在该领域有重叠兴趣的多学科扩展实验室联盟。我们已经建立了测定小鼠微生物瘤的方法，使用16 RNA的454测序，特定细菌类型的FISH标记的细胞荧光分析，以及可能的其他方法，包括微阵列。将需要测序和生物信息学方面的专业知识。我们还启动了无菌小鼠、肠道菌群确定的非生菌小鼠和抗生素治疗后重建的小鼠的研究。最初，我们计划使用MyD88、IL-18、TNF、TLRs等炎症控制基因基因缺陷的小鼠，研究肠道菌群在结肠炎和结肠炎相关癌症的实验模型中的作用。在小鼠实验模型和观察性临床实验中，共生微生物群在与癌症相关的能量改变（即肥胖、恶病质、厌食症）中的作用正在计划中。

In the Section of Cancer Immmunobiology as well as in a few other Sections within the Cancer and Inflammation Program as well as other part of CCR there is great need to understand the role of the gut flora in the pathogenesis of inflammatory and immune colitis and in mouse models of colitis-associated cancer. We extensively use mice deficient for immune or inflammation-related genes and it is always difficult to distinguish a direct effect of those genes on the colitis or cancer, or an indirect one through the regulation of the intestinal flora. Other collaborative studies in the program are directed to the study of the role of the liver immune response in controlling liver carcinogenesis and it is likely that the inflammatory-immunological microenvironment in the liver is also significantly affected by the composition of the intestinal flora. Overall these studies would greatly benefit by the access to a germ free facility and particularly by the availability of committed expertise in gut microbiology based on state of the art sequencing and bioinformatics, expertise that it is of difficult access to single laboratories but that could be efficiently provided to a multidisciplinary extended consortium of laboratories with overlapping interests in this field.We have established methods for the determination of mouse microbioma using 454 sequencing of 16 RNA, cytofluorimetric analysis of FISH labeling of specific bacterial types, and possibly other approaches including microarray. Sequencing and bioinformatic expertise will be needed. We also initiated studies with germ free mice, gnotobiotic mice with defined intestinal flora, and mice reconstitute after antibiotic treatment. Initially we plan to study the role of the intestinal flora in experimental models of colitis and colitis-associated cancer using mice genetically deficient for inflammation-controlling genes such as MyD88, IL-18, TNF, TLRs, and others. The role of commensal microbiota in energetic alteration associated with cancer (i.e. obesiti, cachxia, anorexia) is being planned in murine experimental models and in observational clinical experimentation.