The Emerging Role of the Microbiome in Pediatric Oncology

In this Q&A with Consult QD, Seth J. Rotz, MD, pediatric oncologist in the Department of Pediatric Hematology & Oncology at Cleveland Clinic Children’s, highlights the most important findings about the emerging role of the microbiome in pediatric oncology. The interview has been edited for length and clarity.

What are some of the causes of microbiome dysbiosis in the pediatric oncology setting?

Dr. Rotz: Our understanding of this is, honestly, really incomplete, but we think that there are a couple of main contributors. The first is that oncology patients have a weakened immune system and because of that they’re at risk of infections and are frequently on broad-spectrum antibiotics. The exposure to antibiotics will directly affect the bacteria in the gut and on the skin. We also know that chemotherapy itself can affect the microbiome; we know that most chemotherapy, even without the antibiotics, will reduce the diversity of the microbiome. Finally, there’s the effect of nutrition, such as supplemental nutrition through feeding tubes or IV nutrition that can affect the types of bacteria swimming around in the intestines. There is probably also the effect of the immune system…and the effects of cancer chemotherapy on the immune system.

The effects of microbiome dysbiosis on pediatric cancer and treatment

In what ways can dysbiosis negatively affect pediatric cancer patients?

Dr. Rotz: The most obvious way is through an increased risk of bloodstream infections and the strongest evidence [for this] comes from the bone marrow transplant population, the patients that are really immunocompromised. There were studies of patients who ended up with sepsis where intestinal domination was discovered in their stool. The most common bacterial infections associated with changes in the microbiome is Clostridium deficile, a diarrhea-associated illness. Common bloodstream infections with strains of E. coli, Klebsiella and Enterococcus have all been observed after intestinal domination.

We also know that abnormalities in the microbiome probably play a role in a lot of different things, but our understanding of those is much less complete at this point.

How can the microbiome influence the immune system?

Dr. Rotz: We don’t know the exact reason why dysbiosis influences the immune system, but we do know that certain characteristics of the microbiome can predict graft vs. host disease in HCT, which is a devastating effect of the bone marrow transplant where the donor’s cells attack the host.

How much is known about the effects of the microbiome on the efficacy of cancer therapies?

Dr. Rotz: Immunotherapies may work better or worse depending on different characteristics of the microbiome. A lot of this work has been done [on immune checkpoint inhibitors, ICIs] in melanoma and, thankfully, we don’t have a lot of melanoma in pediatric oncology. But, ICIs are slowly making their way into the treatment of cancers that we see more typically in pediatric oncology, such as Hodgkin’s lymphoma. One of the big questions that remain is: is there a big difference between the pediatric and adult microbiomes? We know that, as we age, our microbiome changes. So, although some of the lessons being learned right now about immunotherapies and the role of the microbiome in adults will probably be transferrable, others may not.

How do the microbiota influence the development of cancer?

Dr. Rotz: The classic tumor where dysbiosis is mostly observed is colon cancer, which is not a typical pediatric tumor. Again, why this happens is less known. We don’t know if the tumor develops because of it or if those bacteria thrive because there is a tumor in the colon. In pediatric oncology, again, the data is much more sparse.

Modulating the microbiome

How can the microbiome be modulated? Is there a future for microbiome modulation in pediatric cancer treatment?

Dr. Rotz: There are several ways to modulate the microbiome and the first one is prevention. There are different strategies to minimize the use of antibiotics and still keep a patient safe. Then there are also prebiotics, delivered either as a pill/supplement or through dietary changes and incorporation of more fiber. We also think that probiotics — such as the good bacteria in yogurt — make for a healthy microbiome. But we don’t really have a ton of great evidence that doing these things absolutely restores the microbiome to a “happy place”.

On the more aggressive side, there is the fecal microbiome transplant (FMT), which entails transplanting good bacteria [from the stool of a healthy donor] into the gut of a patients where they can reestablish a healthy ecosystem. There have been studies of FMT indicating that it may be helpful in a couple of different conditions, such as Clostridium difficile, inflammatory bowel disease and graft versus host disease, although this field is still in infancy. Safety is a big concern [with this procedure], after several recent reports of the transfer of resistant strains in immunocompromised people.