The use of broad-spectrum antibiotics in mice with malignant melanoma, an aggressive kind of skin cancer, increased their metastatic bone development, according to a recent study by researchers at Emory University in Atlanta.
This most likely occurred as a result of the medications’ effects on the mice’s immune system and gut flora. According to one of the study’s authors, Subhashis Pal, Ph.D., a postdoctoral fellow in endocrinology at the Emory University School of Medicine, the findings highlight the significance of the gut microbiome in overall health and suggest that physicians should carefully consider the gastrointestinal effects when using antibiotic therapies to treat cancer or other diseases.
“Any disease or therapy that harms the gut microbiome could have a negative impact on our health,” said Dr. Pal, who presented the report today at the annual meeting of the American Society of Bone and Mineral Research in Austin, Texas, USA.
“In our study we found that the gut microbiome restrains the progression of melanoma bone lesions in mice by promoting the expansion of intestinal natural-killer (NK) cells and T helper (Th1) cells and enhancing their migration to the tumor site,” Dr. Pal said. “Using oral antibiotics depleted the gut microbiome and reduced the population of intestinal NK cells and Th1 cells. This made the mice more vulnerable for tumor growth. They had a higher melanoma tumor burden than control mice whose gut microbiomes were intact.”
Malignant melanoma complications include osteolytic bone metastases. The scientists reasoned that depleting the gut microbiota of mice with antibiotics would disrupt their intestinal immune cells, modify their immunological response, and hasten bone metastases. Mice given broad-spectrum antibiotic treatment had their hearts and bones injected with B16-F10 melanoma cells. Contrary to control mice that had not gotten the injections, the antibiotic injections in those mice increased bone metastasis growth.
Malignant melanoma complications include osteolytic bone metastases. The scientists reasoned that depleting the gut microbiota of mice with antibiotics would disrupt their intestinal immune cells, modify their immunological response, and hasten bone metastases. Mice given broad-spectrum antibiotic treatment had their hearts and bones injected with B16-F10 melanoma cells. Contrary to control mice that had not gotten the injections, the antibiotic injections in those mice increased bone metastasis growth.
The study identified the melanoma’s metastatic growth mechanism. Intestinal NK and Th1 cells’ growth in response to melanoma and their migration from the gut to tumor-bearing bones were both blocked by microbiome removal, according to a flow cytometric examination of Peyer’s patches and bone marrow cells within tumour lesions. Antibiotics significantly reduced the migration of NK and Th1 cells from the gut to the tumour site, as measured directly by NK and Th1 cell migration in Kaede mice, a type that expresses a photo-convertible fluorescent protein that enables direct tracking of intestinal lymphocytes.
This study strongly indicates that microbiome modifications induced by antibiotics might have negative clinical consequences not only with melanoma, but with other diseases as well, Dr. Pal said. “For example, inflammatory bowel disease, or other gut conditions that create inflammation, can lead to increased Th17 cells, TNF producing cell numbers in the gut, which ultimately has a negative impact on our bone health. Similarly, we have seen that in a murine model of surgical menopause, reduced levels of estrogen cause bacterial metabolites to pass more easily through the gut barrier and hyperactivate the immune system. As a result, the number of intestinal and bone marrow cytokine producing T cells rises, largely contributing to the development of bone loss.”
Dr. Pal added: “We should be very much careful with our gut microbiome, and of the unforeseen adverse consequence of antibiotic regimens. Conversely, probiotics can play a major role to maintain healthy gut microbiome, and better overall health.”
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