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The effect of a drug, or the impact of a treatment like chemotherapy, doesn’t just depend on your body. The success of a particular drug also depends on the trillions of bacteria in your gut.
The 100 trillion bacteria that live in the human digestive tract – known as the human gut microbiome – help us extract nutrients from food, boost the immune response, and modulate the effects of drugs.
Recent research, including mine, has implicated the gut microbiome in seemingly unrelated states, ranging from response to cancer treatments to obesity and a host of neurological diseases, including Alzheimer’s disease, Parkinson’s disease, depression, schizophrenia and autism.
What underlies these seemingly inconspicuous observations is the unifying idea that the gut microbiota sends signals beyond the gut, and that these signals have broad effects over a wide band of target tissues.
I am a medical oncologist whose research is to develop new therapies for melanoma. To assess whether changing the microbiome might be of benefit to cancer patients, my colleagues and I evaluated the transfer of feces from melanoma patients who responded well to immunotherapy to patients for whom immunotherapy had failed.
Just appeared in the newspaper Science, our results show that this treatment helped shrink tumors in patients with advanced melanoma when other therapies had not worked.
What connects cancer and gut bacteria?
The gut microbiota has been linked to the success and failure of several cancer treatments, including chemotherapy and cancer immunotherapy with immune checkpoint inhibitors such as nivolumab and pembrolizumab.
In the most recent studies, the species and relative populations of gut bacteria have determined the likelihood of a cancer patient responding to drugs called “immune checkpoint inhibitors”.
This research showed that differences in the gut microbiome between individual patients were associated with varying outcomes for these drugs. But the precise mechanisms underlying microbiome-immune interactions remain unclear.
Can fecal microbes help drugs reach hard-to-treat melanoma?
Oncologists often treat patients with advanced melanoma with immunotherapies targeting specific proteins on the surface of immune cells called PD-1 and CTLA-4. These work in a subset of patients, however – 50 to 70 percent of patients have cancers that get worse despite treatment.
No medical treatment has been approved to treat patients with melanoma who have failed PD-1 immunotherapies.
To determine whether certain types of microbes could increase the effectiveness of PD-1 immunotherapies, my colleagues and I developed a study in which we collected fecal microbes from patients who had responded well to this therapy and administered them to patients. cancer patients who did not benefit from it. checkpoint drugs.
We chose stools from patients who responded well to immunotherapy because they believed they would have higher amounts of bacteria involved in reducing cancer.
(Diwakar Davar / CC BY-ND)
Since it is difficult to identify one or two species of bacteria responsible for the beneficial response to these therapies, we used the entire bacterial community – hence the transplant of fecal microbes.
The transplant recipients were patients whose melanoma had never responded to immunotherapy. Recipients and donors have been screened for disease to ensure that no infectious agent is transmitted during transplantation.
Following a biopsy of their tumor, the patients received a transplant of fecal microbes from patients who received immunotherapy with a medicine called pembrolizumab, which was continued every three weeks.
My colleagues and I evaluated the fecal microbe transplant 12 weeks after treatment. Patients whose cancer had shrunk or remained the same size after transplantation of fecal microbes continued to receive pembrolizumab for up to two years.
Results of a new clinical trial
(Diwakar Davar / CC BY-ND)
Following this fecal microbe transplant treatment, the tumors of six of the 15 patients in the study had tumors that shrank or stayed the same. The treatment was well tolerated, although some patients experienced minor side effects, including fatigue.
When we analyzed the gut microbiota of treated patients, we observed that the six patients whose cancers had stabilized or improved had increased numbers of bacteria that had previously been associated with responses to immunotherapy.
My colleagues and I also analyzed the workers’ blood and tumors. In doing so, we observed that responders had lower levels of unwanted immune cells called myeloid cells, and higher levels of immune memory cells. Additionally, by analyzing proteins in the blood serum of treated patients, we observed reductions in the levels of key immune system molecules associated with resistance in responders.
These results suggest that the introduction of certain intestinal microorganisms into a patient’s colon may help the patient respond to drugs that improve the ability of the immune system to recognize and kill tumor cells.
Ultimately, we hope to move beyond fecal microbe transplants to specific collections of microbes in cancers besides melanoma, paving the way for standardized microbial drug therapy to treat tumors resistant to the disease. immunotherapy. 
Diwakar Davar, Assistant Professor of Medicine, University of Pittsburgh.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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