动物实验,肠道细菌 z-bo 2020-09-14 333

　　Researchers at the Rogers Cancer Center at the University of Michigan are elucidating how microorganisms living in the gastrointestinal tract affect the development of colorectal cancer.

　　They found that certain types of intestinal bacteria are better at stimulating certain immune cells in the body (especially CD8 + T cells) than other types of bacteria. Although these CD8 + T cells can usually help the body fight cancer, overstimulating them may stimulate inflammation and deplete T cells-according to a new mouse model study published in Cell Reports, this actually increases sensitivity to cancer Sex.

　　The first author of the study, Amy Yu, a PhD candidate in immunology at the University of Michigan, said that this work will help scientists find out which bacteria can inhibit or promote tumor growth.

　　Grace Chen, MD, associate professor of hematology/oncology at Michigan Medical University, senior research author, said: "People are also very excited about the role of bacteria in improving the effectiveness of immunotherapy." Roger Cancer center. "This study shows that it may be a double-edged sword-promoting T cell failure is something that researchers need to pay attention to."

　　According to the American Cancer Society, colorectal cancer is the third leading cause of cancer-related deaths in men and women in the United States.

　　Different mice, different results

　　The current research is based on the previous work of Chen's research group, which found that disorders of the gut microbiome can directly promote the development of cancer.

　　The team found that mice from two different research colonies have very different sensitivity to colorectal cancer when exposed to carcinogens and drugs that promote gastrointestinal inflammation.

　　"Mice from the first colony grow an average of five tumors, while mice from the second colony develop 15 tumors and have a more pronounced inflammatory response.

　　When the researchers sequenced fecal bacteria from two different colonies, they found that they had a unique microbial community composed of different types of bacteria.

　　Chen said: "This is exciting because my laboratory is very concerned about which bacteria have the greatest impact on the risk of colorectal cancer, and by what mechanism."

　　Same mice, different results

　　To better understand what caused the differences that the researchers observed in the two different colonies, they transplanted gut bacteria from each of the two colonies into genetically identical mice that reproduce in a bacteria-free environment . Furthermore, the bacterial mice from the second colony performed worse.

　　Yu said: "This shows that different intestinal flora directly promote the development of tumors." "Our data finally revealed nine different bacterial populations, which may have tumor suppressor or tumor-promoting activities."

　　investigation mechanism

　　Next, the research team conducted experiments to better understand what caused the increased inflammation and tumor growth of bacteria from the second mouse colony.

　　Through immune cell analysis, they found that there were bacteria from the second colony in the colon tissue of the mouse, which contained more T cells and more CD8 + cells.

　　Chen said: "This is a bit counterintuitive, because T cells and CD8 + cells usually have a better prognosis in patients with colorectal cancer." "We assume that these cells will be overactivated in the presence of certain bacteria and then depleted. , Which reduces their ability to kill tumor cells."

　　Chen pointed out that when the bacteria from the second mouse colony were transplanted into mice designed to lack CD8 + T cells, the production of tumors would be reduced, thus supporting T cells to promote cancer growth in the presence of certain bacteria. effect.

　　At the same time, the laboratory continues to study the mechanisms by which various bacteria may help promote or prevent the development of colorectal cancer on the basis of research.