Dr Pal, who presented the report today at the annual meeting of the American Society for Bone and Mineral Research in Austin, Texas, US, said: “Any disease or therapy that harms the microbiome said: intestinal flora can have a negative impact on our health.
Dr Pal said. “Oral antibiotic use depletes the gut microbiome and reduces the population of intestinal NK cells and Th1 cells. This makes the mice more vulnerable to tumor growth. They had a higher melanoma burden than control mice with intact gut microbiota.”
Bone metastasis is a complication of malignant neoplasms. The researchers hypothesized that administering antibiotics to deplete the mice’s gut microbiota would affect their gut immune cells and thus alter the immune response of the mice. them, leading to faster bone metastasis. They injected B16-F10 melanocytes into the hearts and bones of mice that had been treated with broad-spectrum antibiotics. As predicted, antibiotic injections accelerated the development of bone metastases in those mice, compared with control mice that were not injected.
Metastatic growth of melanoma: New insights
Research has revealed the mechanism of metastatic development of melanoma. Flow cytometry analysis of Peyer’s plaques and bone marrow cells in tumor lesions revealed that microbiome depletion prevented NK and Th1 cell expansion in the tumor-induced intestine. malignancies and their migration from the intestine to the bone bearing the tumor. Direct measurement of NK and Th1 cell migration using Kaede mice, a strain expressing an image-switching fluorescent protein that allows direct monitoring of lymphocytes in the gut, suggests that antibiotics approximately eight-fold decrease in the migration of NK and Th1 cells from the gut to the tumor site.
When NK cells and Th1 cells leave the gut as part of the body’s immune response, the process is mediated by the S1PR5 and S1PR1 receptors. Pharmacological blockade of cell migration across receptors – involving S1PR5 to NK cells, or S1PR1 to Th1 cells – mimics the effects of antibiotics. The blockade prevented the expansion of NK cells and Th1 cells in the bone marrow and induced a faster development of bone metastases. The circulating NK and Th1 cell lines to the tumor site are directed by the chemokine ligand CXCL9, expressed by bone marrow cells, and CXCR3, expressed by NK and Th1 cells. Complete deletion of CXCR3 or antibody neutralization of CXCL9 reduces the occurrence of tumor NK and Th1 cells and increases tumor growth.
“For example, inflammatory bowel disease or other intestinal conditions that cause inflammation, can lead to an increase in Th17 cells, the number of TNF cells produced in the gut, which ultimately has a negative impact on Similarly, we have seen that in the maternal model of surgical menopause, reduced estrogen levels make it easier for bacterial metabolites to pass through the intestinal barrier and activate immune system. bone loss.”
Dr. Pal added: “We should be extremely careful with our gut microbiome and the unintended adverse consequences of antibiotic regimens. In contrast, probiotics can play a role. important role in maintaining a healthy gut microbiome and overall better health.”