Broad-spectrum antibiotics in malignant melanoma mice An aggressive form of skin cancer accelerates their metastatic bone growth, likely because the drugs deplete the gut microbiota and weaken the immunity of mice, according to a new study by researchers at Emory University in Atlanta. reaction.
The findings underscore the importance of the gut microbiome in overall health and recommend that physicians weigh carefully when using Gastrointestinal effects are administered concurrently with antibiotics in the treatment of cancer or other conditions, said Dr. Subhashis Pal, a postdoctoral fellow in endocrinology at Emory University School of Medicine and one of the authors of the study.
“Any disease or therapy that compromises the gut microbiome can have a negative impact on our health,” Dr. Parr said he presented the report today at the annual meeting of the American Society for Bone and Mineral Research in Austin, Texas
“In our study, we found that the gut microbiome inhibits progression by promoting the expansion of gut natural killer (NK) cells and T helper (Th1) cells and enhancing their migration to the tumor site, thereby reduced melanoma bone lesions in mice,” said Dr. Parr. “Using oral antibiotics depletes the gut microbiota and reduces the number of gut NK cells and Th1 cells. This makes the mice more prone to tumor growth. Compared to control mice with intact gut microbiomes, their melanoma The tumor burden is higher.”
Osteolytic bone metastases are a complication of malignant melanoma. The researchers hypothesized that depleting the mice’s gut microbiota with antibiotics affected their gut immune cells, thereby altering their immune responses, leading to accelerated bone metastases. They injected B16-F10 melanoma cells into the hearts and bones of mice treated with broad-spectrum antibiotics. As predicted, antibiotic injection accelerated the growth of bone metastases in these mice compared to control mice that did not receive the injection.
This study sheds light on the mechanism of metastatic growth of melanoma. Flow cytometric analysis of Peyer’s patches and bone marrow cells within tumor foci showed that microbiome depletion prevented melanoma-induced expansion of intestinal NK and Th1 cells and their migration from the gut to the tumor bone. Direct measurement of NK and Th1 cell migration using Kaede mice, which express a photoconverting fluorescent protein that directly tracks intestinal lymphocytes, showed that antibiotics reduced the migration of NK and Th1 cells from the gut to the tumor site by approximately eight Times.
When NK cells and Th1 cells leave the gut as part of the body’s immune response, the process is controlled by S1PR5 and S1PR1 receptors. Pharmacological blockade of cell migration by receptors including S1PR5 and NK cells, or S1PR1 and Th1 cells mimics the effect of antibiotics. Blockade prevented the expansion of NK cells and Th1 cells in the bone marrow and resulted in accelerated growth of bone metastases.
NK and Th1 cells are directed to the chemokine ligand CXCL9 expressed by myeloid cells and CXCR3 expressed by NK and Th1 cells. tumor site. Global deletion of CXCR3 or antibody neutralization of CXCL9 reduced tumor NK and Th1 cell frequencies and increased tumor growth.
This study strongly suggests that antibiotic-induced microbiome modification may not only have a negative clinical impact on melanoma, Dr. Pal said. And it has negative effects on other diseases as well. “For example, inflammatory bowel disease or other intestinal diseases that cause inflammation can lead to increased numbers of Th17 cells, TNF-producing cells, in the gut, which ultimately negatively affects our bone health. Similarly, we have demonstrated in a mouse model of surgical menopause In humans, lower estrogen levels lead to easier passage of bacterial metabolites across the gut barrier and over-activation of the immune system. As a result, the number of T cells producing gut and bone marrow cytokines increases, which largely contributes to bone loss.”
Dr. Pal added: “We should be very careful about our gut microbiome, and the Unforeseen adverse consequences. Instead, probiotics can play an important role in maintaining a healthy gut microbiome and improving overall health.”
provided by the American Association for the Study of Bone and Minerals
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