Microbiota transplant alleviates colitis in certain cancer patients

Immunotherapy is a mainstay in the treatment of various tumors, such as melanoma, non-small cell lung cancer, and genitourinary cancer.. The administration of checkpoint inhibitors – drugs that lift the brakes on a patient's immune system to attack cancer – has added survival, thanks to this innovative self-defense strategy, but has also brought new side effects and toxicities. to cancer plants.

One of them is immune-mediated colitis. In fact, the gastrointestinal tract is among the organs most affected by checkpoint inhibitors, and this results in diarrhea and colicky abdominal pain of varying intensity.

Patients suffering from these symptoms have to discontinue cancer treatment or resort to immunosuppressive drugs.. In both cases, there is a risk of compromising the results of the treatment.

But there could be another possibility or at least those are being studied.. A team of researchers at the University of Texas MD Anderson Cancer Center in Houston has conducted a trial of twelve patients showing that fecal microbiome transplants from healthy donors reduce intestinal inflammation, diarrhea, and more intestinal side effects of immunotherapy.

Achieve remission in more than 90% of cases

More than half of the patients with severe colitis or diarrhea who did not respond to conventional treatments experienced a remission in symptoms. Ten of them showed clear improvement and seven complete responses.

At the end of the study, 92% of the patients were in clinical remission.. Details of the work led by Yinghong Wang, a gastroenterology specialist at MD Anderson, can be found in the pages of Science Translational Medicine.

As Jordi Guardiola, head of the Digestive System Service and the Inflammatory Bowel Disease Unit of the Bellvitge University Hospital in Barcelona explains, colitis associated with immunotherapeutic drugs is caused by an exacerbation of the patient's immunity; “It has nothing to do with the digestive symptoms that chemotherapy causes by affecting the intestinal mucosa, for example.”

Guardiola is a pioneer in Spain in the study of the microbiome and promoter of the Transversal Unit for the Study of the Human Microbiome at Hospital de Bellvitge, where a multidisciplinary team investigates microbiota transplantation and its potential application in different pathologies.

Remember that when immune-mediated colitis occurs, symptomatic treatment is resorted to: “Some patients respond quickly to glucocorticoids and do not need more. If not, we use biologic drugs, which are also used in inflammatory bowel disease.”

The study included patients where standard treatments have failed. “The interesting thing about the work”, Jordi Guardiola clarifies, “is that they achieve success in refractory patients with a treatment that is not immunosuppressive, but is based on the modulation of the microbiome”.

In line, he mentions that in other “preliminary and therefore cautious” research, it has been observed how the modulation of the microbiota can translate into a better response of patients to immunotherapy.

“Even if these observations don't end up generating a change in clinical practice, they will teach us a lot about why some patients respond and others don't.”

How safe is the procedure?

A priori it may give some qualms to administer millions of microbes to a cancer patient. Fecal microbiome transplantation is not a risk-free procedure. However, Guardiola adds, the possibility of transferring multi-resistant germs that end up causing severe sepsis is eliminated by screening the donated material.

In addition, he adds that a systematic review by gastroenterologist Gianluca Ianiro, from the Catholic University of Rome, found after analyzing almost 6,000 fecal microbiota transplants that it is a safe procedure.

At the moment, it is only indicated to treat recurrent Clostridium difficile infection, although its potential efficacy is being investigated in multiple fields.

The review concluded that mild and transient adverse effects (flatulence, bloating) occur in one in five patients, and serious ones in 1%, mostly related to procedures that may sometimes be required to transfer the microbiota (sedation, intubation).

Convey the predisposition

“It is a safe therapy”, affirms Jordi Guardiola. “Actually, what worries us most now is not the potential short-term adverse effects, but the possibility of transmitting the predisposition to disease.”

Since the intestinal microbiota has been associated with all kinds of diseases (from diabetes to depression), it is conceivable that the risk of developing a pathology can be transmitted.

“That is why it is so important to have transplant traceability records, to detect the possibility of a disease occurring. I think it's unlikely, but we have to keep an eye on it.”