Study finds antibiotics can make melanoma worse by depleting the gut microbiome

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Use of broad-spectrum antibiotics in mice with malignant melanoma, an aggressive form of skin cancer, accelerated their metastatic bone growth, likely because the drugs depleted the mice’s gut flora and weakened their immune response , according to a new study by Emory researchers. Atlanta University.

The findings underscore the importance of the gut microbiome in overall health and suggest physicians should carefully weigh gastrointestinal effects when using antibiotic therapies while treating cancer or other diseases, one of the researchers said. Study authors, Subhashis Pal, Ph.D., a postdoctoral fellow in endocrinology at Emory University School of Medicine.

“Any disease or therapy that harms the gut microbiota 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,” said 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 using antibiotics to deplete the gut microbiome of mice would affect their gut immune cells and thereby alter their immune response, leading to accelerated bone metastasis. They injected B16-F10 melanoma cells into the hearts and bones of mice that had been treated with broad-spectrum antibiotics. As expected, the antibiotic injections accelerated metastatic bone growth in these mice, compared to control mice that did not receive the injections.

The study revealed the mechanism of metastatic growth of melanoma. Flow cytometry analysis of Peyer’s patches and bone marrow cells in tumor lesions revealed that microbiome depletion prevented melanoma-induced expansion of intestinal NK and Th1 cells and their migration from the gut to tumor-bearing bones. Direct measurement of NK and Th1 cell migration using Kaede mice, a strain expressing a photo‐convertible fluorescent protein that allows direct tracking of intestinal lymphocytes, revealed that antibiotics decreased migration approximately eight-fold NK and Th1 cells from the intestine 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 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 increased Th17 cell counts, TNF producing cell counts in the gut, which ultimately negatively 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. the number of intestinal and bone marrow cytokine-producing T cells increases, contributing greatly to the development of bone loss.”

Dr Pal added: “We need to be very careful about 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.


The oral microbiome contributes to healthy jawbones by influencing immune cell interactions with bone cells


Provided by the American Society for Bone and Mineral Research

Quote: Study finds antibiotics can worsen melanoma by depleting the gut microbiome (September 11, 2022) Retrieved September 12, 2022 from https://medicalxpress.com/news/2022-09-antibiotics-melanoma-worse-depleting-gut .html

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