A new study in mice suggests that antibiotics may accelerate the growth of bone-spread melanoma by disrupting the gut microbiota and weakening the immune response. Journal of Clinical Investigation Presented at the American Bone Mineral Research (ASBMR) 2022 Annual Meeting.

The microbiome in health and disease

The gut microbiome is a collection of trillions of microorganisms, including bacteria, viruses and fungi, that live in the gut. Bacteria are the best-studied members of our gut microbiome, with an estimated 200 to 1000 species of bacteria living in our gut.Studies have shown that the composition of the gut microbiota can affect the body’s health during illnesss Such as autoimmune diseases and inflammatory bowel disease. In addition, the microbiome is involved in bone tissue health, including regulation of bone density, skeletal development, and osteoporosis (weakening of bones).

Many types of cancer often spread (metastasize) to distant parts of the body, including melanoma, an aggressive skin cancer that often spreads to the bones. Her 5-year survival rate for patients who have metastasized is usually only 30%. Importantly, microbiome disruption and imbalance (known as dysbiosis) is associated with cancer progression, but the role of the microbiome in bone tumor growth is unclear.

In the current study, Emory University researchers used a mouse model to investigate how the microbiome influences immune responses and bone melanoma growth.

Microbiome disruption increases bone tumor growth

Scientists modeled the spread of melanoma to bone by injecting human melanoma cells directly into the heart (intracardiac) or into the tibia of the mouse leg (intratibia). Their microbiomes were depleted using a cocktail of broad-spectrum antibiotics, including ampicillin, vancomycin, and metronidazole.The results of the trial showed that antibiotic treatment eliminated more than 99% of their microbiome, and they were treated with antibiotics. They found that treated mice had significantly higher tumor growth compared to untreated controls.

To rule out accidental ‘off-target’ effects of antibiotics that may promote tumor growth, researchers are using so-called ‘non-absorbable’ antibiotics (acting locally in the intestine and The experiment was repeated using a drug that is not absorbed into body. These also depleted the microbiome, resulting in increased tumor growth.

But what was the mechanism that caused this? The team investigated two types of immune cells known to act in the immune response to melanoma: natural killer (NK) cells and T helper 1 (Th1) cells, and what role they play in this phenomenon. I checked to see if there were any. They showed that the presence of bone tumors increased the number of NK and Th1 cells in the bone marrow. However, antibiotic-induced microbiome depletion hampered this increase. Furthermore, using Kaede mice (a special mouse strain that produces a fluorescent signal in these cells) to visualize NK and Th1 cells, we found that antibiotics reduce migration of NK and Th1 cells from the gut to the tumor. Proven. This therefore suggests that antibiotic-induced microbiome alterations may alter the immune response against cancer cells in bone.

Overall, these results indicate that there is a level of iliac crosstalk in immune responses. Subhashis Pal, Ph.D., lead author of the study and fellow at Emory University School of Medicine, said: technology network about the results. “Our findings showed that antibiotic-induced gut microbiota depletion accelerated bone metastasis of melanoma,” explained Pal. “Depletion of the gut microbiome prevented melanoma-induced expansion of gut NK and Th1 cells and their migration from the gut to tumor-bearing bone.”

Does this apply to other cancer types as well?

The results of this study strongly suggest a role for the microbiome in regulating the immune response to bone tumors and suggest that antibiotic use may adversely affect melanoma patients with bone metastases. increase.

Nonetheless, Pal and colleagues plan to investigate to what extent these findings apply not only to human patients, but also to other types of cancer. “We are continuously working to better understand the gut-bone crosstalk during bone metastasis. Currently, using a breast cancer model, we are demonstrating that the gut microbiota is associated with bone metastasis in breast cancer. We also plan to study the effects of the human microbiome on tumor growth using clinical samples from cancer patients.

Dr. Subhashis Pal was talking with Sarah Whelan, Science Writer at Technology Networks.

reference: Pal S, Perien DS, Yumoto T, et al Microbiome suppresses melanoma bone growth by promoting homing of intestinal NK and Th1 cells to bone. J Clean Invest2022;132(12). Doi: 10.1172/JCI157340