free counter
Health And Medical

Study finds antibiotics could make melanoma worse, by depleting the gut microbiome

antibiotic
Credit: CC0 Public Domain

The usage of broad-spectrum antibiotics in mice with malignant melanoma, an aggressive type of skin cancer, accelerated their metastatic bone growth, likely as the drugs depleted the mice’s intestinal flora and weakened their immune response, in accordance with a fresh study by researchers at Emory University in Atlanta.

The findings underscore the significance of the in general health and claim that doctors should carefully weigh the gastrointestinal effects if they use antibiotic therapies while treating cancer or other diseases, said among the study’s authors, Subhashis Pal, Ph.D., a postdoctoral fellow in endocrinology at the Emory University School of Medicine.

“Any disease or therapy that harms the gut may have a negative effect on our health and wellness,” said Dr. Pal, who presented the report today at the annual meeting of the American Society of Bone and Mineral Research in Austin, Texas, U.S..

“Inside our study we discovered that the gut microbiome restrains the progression of melanoma lesions in mice by promoting the expansion of intestinal natural-killer (NK) 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 populace of intestinal NK cells and Th1 cells. This made the mice more vulnerable for . That they had an increased melanoma tumor burden than control mice whose gut microbiomes were intact.”

Osteolytic bone metastasis is really a complication of . The researchers hypothesized that using antibiotics to deplete the gut microbiome of mice would affect their intestinal immune cells and therefore alter their , resulting in accelerated bone metastasis. They injected B16F10 melanoma cells in to the hearts and bones of mice that were treated with broadspectrum antibiotics. As predicted, the antibiotic injections accelerated bone metastatic growth in those mice, weighed against control mice that hadn’t received the shots.

The analysis revealed the mechanism for the metastatic growth of melanoma. Flow cytometric analysis of Peyer’s patches and bone-marrow cells within tumor lesions revealed that microbiome depletion prevented the melanomainduced expansion of intestinal NK and Th1 cells and their migration from the gut to tumorbearing bones. Direct measurement of NK and Th1 cells migration using Kaede mice, a strain expressing a photoconvertible fluorescent protein which allows direct tracking of intestinal lymphocytes, revealed that antibiotics decreased by about eightfold the migration of NK and Th1 cells from the gut to the tumor site.

When NK cells and Th1 cells leave the gut within the body’s immune response, the procedure is mediated by S1PR5 and S1PR1 receptors. Pharmacological blockade of the cells’ migration via the receptorsinvolving S1PR5 with NK cells, or S1PR1 with Th1 cellsmimicked the consequences of antibiotics. The blockade prevented expansion of NK cells and Th1 cells in the bone marrow and caused accelerated bone metastasis growth.

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

This study strongly indicates that microbiome modifications induced by antibiotics may have negative clinical consequences not merely with melanoma, but with other diseases aswell, Dr. Pal said. “For instance, , or other gut conditions that induce inflammation, can result in increased Th17 cells, TNF producing cell numbers in the gut, which ultimately includes a negative effect on our bone health. Similarly, we’ve seen that in a murine style of surgical menopause, reduced degrees of estrogen cause bacterial metabolites to pass easier through the gut barrier and hyperactivate the disease fighting capability. Consequently, the amount of intestinal and cytokine producing T rises, largely adding to the development of bone loss.”

Dr. Pal added: “We have to be quite definitely careful with this gut microbiome, and of the unforeseen adverse consequence of antibiotic regimens. Conversely, probiotics can play a significant role to keep healthy gut microbiome, and better general health.”



Provided byAmerican Society for Bone and Mineral Research

Citation: Study finds antibiotics could make melanoma worse, by depleting the gut microbiome (2022, September 11) retrieved 12 September 2022 from https://medicalxpress.com/news/2022-09-antibiotics-melanoma-worse-depleting-gut.html

This document is at the mercy of copyright. Aside from any fair dealing for the intended purpose of private study or research, no part could be reproduced minus the written permission. This content is provided for information purposes only.

Read More

Related Articles

Leave a Reply

Your email address will not be published.

Back to top button

Adblock Detected

Please consider supporting us by disabling your ad blocker