Antibiotics can make skin cancer worse

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Researchers believe this is because antibiotics deplete the gut flora and weaken their immune response.

According to a new study, the use of antibiotics can make melanoma worse by damaging the gut microbiome.

According to a recent study by researchers at Emory University in Atlanta, the use of broad-spectrum antibiotics in mice with malignant melanoma, an aggressive type of skin cancer, accelerated their metastatic bone growth. This was likely because the drugs depleted the mice’s gut flora and weakened their immune response.

According to one of the study authors, Subhashis Pal, Ph.D., a postdoctoral fellow in endocrinology at Emory University School of Medicine, the findings highlight the importance of the gut microbiome in overall health. and suggest that physicians should carefully consider gastrointestinal adverse effects when using antibiotic therapies to treat cancer or other diseases.

“Any disease or therapy that harms the gut microbiome could negatively impact our health,” said Dr. Pal, who presented the report today at the American Society of Bone and Mineral Research’s annual meeting in Austin, Texas, USA.

“In our study, we found that the gut microbiome inhibits the progression of melanoma bone lesions in mice by promoting the expansion of intestinal natural killer (NK) cells and helper T cells (Th1) and enhancing their migration to the tumor site,” says Dr. Pal. “The use of oral antibiotics depleted the gut microbiome and reduced the population of intestinal NK cells and Th1 cells. This made the mice more vulnerable to tumor growth. They had a higher melanoma tumor burden than the mice controls whose gut microbiomes were intact.

Osteolytic bone metastasis is a complication of malignant melanoma. The researchers hypothesized that depleting mice’s gut microbiota with antibiotics would impact their gut immune cells and consequently alter their immune response, leading to accelerated bone metastasis. They injected B16F10 melanoma cells into the hearts and bones of mice treated with broad-spectrum antibiotics. Antibiotic injections, as expected, increased bone metastatic growth in these animals compared to control mice that did not receive the treatments.

Research has revealed the mechanism of metastatic growth of melanoma. Flow cytometry analysis of Peyer’s patches and bone marrow cells within tumor lesions demonstrated that microbiome depletion inhibited melanoma-induced expansion of intestinal NK and Th1 cells and their migration from the intestine to the tumour-bearing bones. Direct measurement of NK and Th1 cell migration using Kaede mice, a strain expressing a photoconvertible fluorescent protein that allows direct tracking of intestinal lymphocytes, revealed that antibiotics reduced cell migration approximately eight-fold NK and Th1 from gut to tumor site.

When NK cells and Th1 cells leave the gut as part of the body’s immune response, the process is mediated by S1PR5 and S1PR1 receptors. Pharmacological blockade of cell migration via receptors – involving S1PR5 with NK cells or S1PR1 with Th1 cells – mimicked the effects of antibiotics. The blockade prevented the expansion of NK cells and Th1 cells in the bone marrow and caused accelerated growth of bone metastases.

The influx of circulating NK and Th1 cells to the tumor site is driven by the chemokine ligand CXCL9, which is expressed by bone marrow cells, and CXCR3, which is expressed by NK and Th1 cells. Global deletion of CXCR3 or neutralization of CXCL9 antibodies decreased the frequency of NK and Th1 tumor cells and increased tumor growth.

This study strongly indicates that antibiotic-induced changes in the microbiome could have negative clinical consequences not only with melanoma but also with other diseases, Dr. Pal said. “For example, inflammatory bowel disease or other bowel conditions that create inflammation can lead to an increase in Th17 cell counts, with TNF producing cell counts in the gut, which ultimately has a negative impact on the health of our bones. Similarly, we have seen that in a mouse model of surgical menopause, reduced levels of estrogen make it easier for bacterial metabolites to pass through the intestinal barrier and overactivate the immune system. As a result, the number of intestinal and bone marrow cytokine-producing T cells increases, largely contributing to the development of bone loss.

Dr Pal added: “We have to be very careful with our gut microbiome and the unintended adverse consequences of antibiotic regimens. Conversely, probiotics can play a major role in maintaining a healthy gut microbiome and better overall health.

Meeting: American Society for Bone and Mineral Research 2022 Annual Meeting

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