Antibiotics can worsen skin cancer

According to a new study, antibiotic use may worsen melanoma
by disrupting the gut microbiota.

According to a recent study by researchers at Emory University in Atlanta, applying broad-spectrum antibiotics to mice with malignant melanoma, an aggressive form of skin cancer, accelerated their metastatic bone growth
.
This is most likely because the drug depleted the rats' gut flora, weakening their immune response
.

Dr.
Subhashis Pal, one of the study's authors and a postdoctoral fellow in endocrinology at Emory University School of Medicine, said the findings underscore the importance of the gut microbiome in overall health and recommend that doctors carefully consider the impact of
the gut when using antibiotic therapy to treat cancer or other conditions.

"Any disease or therapy that damages the gut microbiota can negatively impact our health," said Dr.
Pal, who presented the report
today at the annual meeting of the American Society for Bone and Mineral Research in Austin, Texas.

Dr Pal said: "In our study, we found that the gut microbiome inhibits the progression
of melanoma osteopathies in mice by promoting the expansion of natural intestinal killer cells (NK) and T helper cells (Th1) and enhancing their migration to tumor sites.
The use of oral antibiotics depletes the gut microbiota and reduces the number of
intestinal NK cells and Th1 cells.
This makes it easier for mice to grow tumors
.
They had a higher melanoma burden
than control mice with intact gut microbiota.
”

Osteolytic bone metastases are a complication
of malignant melanoma.
The researchers hypothesized that depleting the gut microbiota of mice with antibiotics affected their gut immune cells, altering their immune response and leading to accelerated bone metastasis
.
They injected B16F10 melanoma cells into the hearts and bones of mice treated with broad-spectrum antibiotics
.
Compared to control mice not treated with antibiotics, antibiotic injections increased bone metastasis growth
in these animals.

Studies have revealed the mechanism
of metastatic growth of melanoma.
Flow cytometry analysis of Peyer plaques and bone marrow cells within tumor lesions found that the reduction in the microbiome inhibited melanoma-induced expansion of intestinal NK cells and Th1 cells and their migration
from the gut to the tumor carrier bone.
Direct measurements of NK cell and Th1 cell migration using Kaede mice, a strain expressing a light-convertible fluorescent protein capable of directly tracking intestinal lymphocytes, found that antibiotics reduced the migration of NK cells and Th1 cells from the gut to the tumor site by about 8-fold
.

When NK cells and Th1 cells leave the intestine as part of the body's immune response, this process is mediated by S1PR5 and S1PR1 receptors
.
Pharmacological blockade of cell migration through receptors—including S1PR5 and NK cells, or S1PR1 and Th1 cells—mimicked the effects of
antibiotics.
Blocking blocks the proliferation of NK cells and Th1 cells in the bone marrow and accelerates bone metastasis growth
.

Circulating NK and Th1 cell flow to the tumor site is guided by the chemokine ligands CXCL9 and CXCR3, which are expressed in bone marrow cells and CXCR3 in
NK and Th1 cells.
Global deletion of CXCR3 or neutralization of antibodies to CXCL9 reduces the frequency of tumor NK and Th1 cells and increases tumor growth
.

Dr Pal said the study strongly suggests that the microbiome changes caused by antibiotics may have negative clinical consequences
not only for melanoma, but also for other diseases.
"For example, inflammatory bowel disease or other intestinal diseases that cause inflammation can lead to an increase in Th17 cells, which is the number of TNF-producing cells in the gut that ultimately negatively affects
our bone health.
" Similarly, we have seen that in a mouse model of surgical menopause, reduced estrogen levels lead to easier passage of bacterial metabolites through the intestinal barrier and highly activate the immune system
.
Therefore, the number of cytokine-producing T cells in the intestine and bone marrow increases, which greatly contributes to the development of
bone loss.
”

Dr Pal added: "We should be very careful about our gut microbiota, as well as the unforeseen adverse consequences
of antibiotic regimens.
Instead, probiotics can play an important role
in maintaining a healthy gut microbiome and better overall health.
”