Exploring the Connection Between Microbiomes and Cancer Treatment

Dr. Marcel van den Brink, a specialist in blood-related cancers like leukemia, has been refining a complex and delicate process since the early ’90s. Many of his patients underwent allogenic hematopoietic cell transplants, a procedure that involves erasing the patient’s existing immune system with strong chemotherapy, allowing donor cells to take over. Until the new cells establish themselves, patients are extremely vulnerable.

These transplant patients often spent extended periods in tightly controlled environments shielded from pathogens. Van den Brink recalls how nurses and family interacted with patients through gloves that extended through plastic barriers. To maintain a sterile environment until the immune system was restored, patients received heavy doses of broad-spectrum antibiotics. However, despite stringent precautions, many faced complications; in the 1990s, around a quarter of these patients died from infections or graft-versus-host disease, where the new immune cells attacked the body’s tissues.

Reflecting on these outcomes, van den Brink notes, “We recognized that some of this was self-inflicted. Our aggressive treatment caused significant collateral damage.” This awareness contributed to a burgeoning research field examining the relationship between gut microbes and immune function.

This focus gained momentum recently when U.S. Health and Human Services Secretary Robert F. Kennedy Jr. attended a research symposium at the City of Hope Cancer Center in California, where van den Brink is now president. NIH Director Dr. Jay Bhattacharya described the latest findings in this area as “mind-blowing.”

The symposium, dubbed “the next frontier of cancer prevention and care,” highlighted ongoing research into manipulating the gut microbiome to enhance cancer treatment. Nearly 100 studies are currently underway to explore this connection.

Research has shown that microbiomes significantly influence immunotherapy outcomes. In a groundbreaking move, a kidney cancer patient at University Hospitals Seidman Cancer Center is set to be the first participant in a trial that tests probiotics to enhance cancer treatment. The study will involve 700 participants who will take CBM588, a strain of bacteria known as Clostridium butyricum, along with their regular immunotherapies. This strain is already well-established in Japan as a dietary supplement for gastrointestinal concerns.

Dr. Pedro Barata, one of the study’s lead researchers, emphasizes their ambition, stating, “We aim to redefine the standard of care.” Preliminary studies hinted at success; one at City of Hope found that CBM588 could improve outcomes for renal cell carcinoma patients receiving immune treatments.

Dr. Sumanta Pal, a co-investigator on the current trial, recounts how his interest in microbiomes sprouted over a decade ago when conversations with biostatistician Dr. Paul Frankel revealed fascinating parallels between livestock health and gut bacteria. Frankel shared insights about poultry operations where fewer cleanings of litter led to healthier birds, suggesting the benefits of maintaining gut bacteria through probiotics.

Commercial agriculture may not often publish research on these practices, but recent changes to limit unnecessary antibiotic use align closely with the findings that overuse contributes to drug-resistant bacteria. Cancer researchers are now more cautious about antibiotic usage, acknowledging its profound impact on gut health. Pal comments, “We cautiously consider the implications of antibiotic stewardship and encourage doctors to reflect on the necessity of their prescriptions.”

In the realm of hematopoietic cell transplants, van den Brink and colleagues analyzed over 1,300 fecal samples. They noted a direct connection between dysbiosis—an imbalance in gut bacteria—and mortality rates in patients. Dysbiosis was also linked to diminished survival rates for patients undergoing autologous transplants, which involve using the patient’s own cells post-chemotherapy.

The causes behind these links remain complex, and many questions linger, such as how the absence of beneficial bacteria can pave the way for harmful species to thrive. Van den Brink has observed instances where patients’ gut bacteria were reduced to a single strain, highlighting a drastic shift from a diverse ecosystem to near sterility.

Food’s Impact on Immunity

The role of diet deserves attention too. A 2021 study from the University of Texas MD Anderson Cancer Center indicated that patients consuming high-fiber diets saw better treatment responses for melanoma, with risk reductions in cancer progression or mortality corresponding to higher fiber intake.

As van den Brink explains, the human gut, rich in various bacteria, is where T-cells and B-cells—key immune components—thrive, establishing a crucial learning ground for the immune system. The challenge is how to maintain this balance in immunocompromised patients heavily reliant on antibiotics.

For years, guidelines advised patients to steer clear of fresh produce for fear of contamination. Van den Brink admits that his past recommendations— advocating for energy drinks—were misguided. They learned that a diet high in sugar could fuel harmful bacteria, which prompted a shift in their approach.

Now, City of Hope has revamped its menu. Patients like Kimberly Shipman, recovering from a leukemia transplant, found joy in fresh options like an organic beet salad. “I’ve been eating so well,” she shares, highlighting how the hospital’s food service has improved.

New patients receive immediate consultation with a nutritionist to promote healthier eating. While still cautious about fresh foods that may pose contamination risks, patients are encouraged to consume washed fruits and vegetables. Research suggests that a nutritious diet can enhance responses to immunotherapy.

Dr. Robert Jenq, who oversees the Microbiome Program at City of Hope, explains that certain gut bacteria can convert fiber into short-chain fatty acids, potentially enhancing immune function and reducing inflammation.

In a novel trial, Dr. Jenny Paredes plans to provide high-fiber meals to hematopoietic cell transplant patients, analyzing their dietary impact during their hospital stay and subsequent recovery. Her goal is to collect insights on preserving microbiome balance to optimize treatment strategies.

However, the endeavor faces challenges. The complexity of the gut microbiome, which includes hundreds of bacterial species along with viruses, adds layers to the understanding of how they interact under various conditions.

Fecal microbiota transplants are increasingly seen as a way to harness the potential of these microbial landscapes. Rashidi is currently studying the effects of fecal microbiota transplants on patients having hematopoietic cell transplants, involving the use of screened, purified feces from healthy donors.

While earlier findings indicated that these transplants could correct dysbiosis, there remain gaps in understanding their efficacy in infection prevention. “I’m intrigued by the microbiome’s ability to heal but puzzled about the underlying mechanisms,” Rashidi admits.

Though fecal transplants have a history stretching back to ancient times, they are now used clinically to combat severe colon inflammation due to infections like C. difficile. More than 40 cancer trials are currently exploring fecal microbiota transplants to improve immunotherapy responses.

Elkrief points out that patients experiencing toxicities related to immunotherapy showcase distinct microbiome compositions compared to those who don’t, indicating that restoring a healthy microbiome might be key to effective treatment.

While the FDA has approved some fecal transplant products, there are commercial groups working to refine them further. Some these are “synthetic fecal transplants,” designed to mimic the microbial balance of healthy individuals or previous patients who successfully responded to treatments.

Ultimately, research has opened new avenues for exploring how diet and microbiomes can influence cancer treatment. But the field is still young, and understanding the intricacies of these interactions will require continued exploration.

Van den Brink remains hopeful, stating, “We’re seeking to evolve diet into a powerful therapeutic tool, though we’re still in the early stages of understanding how to achieve that.”