The gut microbiome—the trillions of bacteria and other microorganisms that live in our intestines—plays an extensive role in human health and disease. An imbalance between healthy and unhealthy gut bacteria has been linked to a wide variety of adverse health conditions, including irritable bowel syndrome, inflammatory bowel disease, obesity, and type 2 diabetes. And conversely, a healthy gut microbiome has been linked to lower risk of disease, including reduced cholesterol and heart disease risk.
Research shows that diet plays a key role in keeping the gut microbiome healthy and in balance, especially a diet rich in probiotic-rich fermented foods and high-fiber prebiotics (food for probiotic bacteria). Probiotic supplements, too, have been investigated both for their ability to promote a healthy gut microbiome and perhaps to prevent disease.
But the health benefits of probiotics might also run to the therapeutic, according to new research from City of Hope National Medical Center in Los Angeles that investigated the possible benefits of a targeted probiotic added to conventional cancer treatment. The results of the study were published in Nature Medicine in June.
The City of Hope study focused on a live biotherapeutic product known as CBM588, which is a probiotic containing a specific strain of Clostridium butyricum known for its potential immunomodulatory and anti-inflammatory effects. In the single-center, Phase I trial, researchers recruited 30 people with recently diagnosed metastatic kidney cancer. Participants were randomized to receive conventional immunotherapy with or without the addition of an oral supplement of CBM588.
Participants’ gut microbiomes were analyzed via stool samples in the beginning for a baseline and then 13 weeks into treatment, with researchers looking specifically for evidence of a change in the relative abundance of Bifidobacterium spp. The researcher also evaluated certain efficacy measures, such as objective response rate (ORR), progression-free survival (PFS), and toxicity profile.
While analysis did not show an appreciable increase in Bifidobacteria abundance, researchers did note an increase of bacteria in the Ruminococcaceae family, which has previously been associated with improved clinical outcomes. Analysis also indicated statistically significant improvements in several efficacy measures, leading researchers to conclude that the addition of CBM588 to conventional treatment may improve patient outcomes.
Conclusions
“We at City of Hope are the first to demonstrate a live bacterial product’s ability to improve clinical outcomes for patients with kidney cancer treated with immunotherapy,” said corresponding author Sumanta Pal, MD. “CBM588 could be exciting in cancer treatment because of its potential to enhance the efficacy of immune checkpoint inhibitor-based treatment, improve patient outcomes, and modulate the gut microbiota in beneficial ways.”
While acknowledging the study’s small sample size as a limiting factor, Pal’s team stresses that the results are promising enough to spur further research. They are currently at work designing Phase II/III clinical trials to assess the novel use of CBM588 and microbiome modulation in people with advanced cancer.
“Ongoing and larger clinical trials are crucial to validate these benefits and address current challenges,” said Pal. “If the positive results…are confirmed, CBM588 could become a valuable supplement in the treatment of various cancers, particularly for patients treated with immune checkpoint inhibitors.”
“While not yet part of standard cancer treatment protocols, microbiome modulation is a promising area of research with the potential to enhance the efficacy of cancer therapies, particularly immunotherapies,” said Hedyeh Ebrahimi, MD, MPH, the study’s lead author. “Current applications are primarily within clinical trials, but the growing body of evidence suggests that microbiome-based interventions may soon become a valuable component of cancer treatment strategies.”
