Exploring the promising connection between CBM588, the gut microbiome, and immunotherapy outcomes
In the relentless battle against cancer, scientists are exploring an unexpected frontier: the human gut. Within our digestive systems lives a vast universe of microorganisms—the gut microbiome—that appears to play a crucial role in how our bodies respond to cancer treatments. Recent groundbreaking research has revealed that modifying this microbial ecosystem with a specific bacterial supplement might significantly improve outcomes for patients with metastatic renal cell carcinoma (mRCC), the most common form of kidney cancer. This article explores the fascinating science behind this discovery and what it means for the future of cancer therapy.
The human body is home to trillions of microorganisms, collectively known as the microbiome. With approximately 38 trillion bacterial cells, our microbial inhabitants nearly equal the number of human cells in our bodies 1 . The largest concentration of these microbes resides in our gastrointestinal tract, particularly the colon, which hosts bacteria, viruses, and fungi that form a complex ecosystem essential to our health.
This microbial community is not just along for the ride—it performs crucial functions that keep us healthy. The gut microbiome helps with nutrient metabolism, maintains the intestinal barrier, and plays a fundamental role in educating and regulating our immune system 1 . The constant communication between our gut bacteria and immune cells helps determine how our bodies respond to threats—including cancer cells.
When the microbial community falls out of balance (a condition called dysbiosis), it can contribute to various diseases, including inflammatory conditions and potentially cancer 1 . Conversely, a healthy, diverse microbiome appears to support overall health and proper immune function.
Kidney cancer remains a significant health burden, with approximately 82,000 new cases diagnosed in the United States each year 1 . When the disease spreads beyond the kidney (becomes metastatic), treatment traditionally has involved targeted therapies and immunotherapy drugs called immune checkpoint inhibitors (ICIs).
These treatments have revolutionized mRCC care, but they still have significant limitations. Despite these advances, the five-year survival rate for metastatic kidney cancer remains around 15% 1 . Additionally, treatment response is highly variable—some patients experience complete remission while others see little benefit 1 .
Oncologists noticed that the composition of a patient's gut microbiome seemed to influence how they responded to immunotherapy. Subsequent research across different cancer types, including melanoma and lung cancer, revealed that patients with certain beneficial bacterial species in their gut tended to respond better to ICIs 1 . This raised an intriguing question: Could modifying the gut microbiome improve cancer treatment outcomes?
CBM588 is a live bacterial product containing a strain of Clostridium butyricum, a bacterium that naturally occurs in healthy human guts 3 . Unlike probiotics that contain multiple bacterial strains, CBM588 is a targeted biotherapeutic that has been used for decades in Japan for various gastrointestinal disorders 3 .
The potential anticancer mechanism of CBM588 is fascinatingly indirect. Rather than attacking cancer cells itself, CBM588 appears to create a more favorable environment in the gut for other beneficial bacteria to thrive 3 .
Specifically, CBM588 produces butyrate, a short-chain fatty acid that has multiple beneficial effects:
Additionally, CBM588 fosters the growth of Bifidobacterium species—beneficial bacteria that have been associated with better response to immunotherapy in previous studies 3 .
Researchers conducted two pioneering clinical trials to evaluate whether CBM588 could enhance the effectiveness of standard immunotherapy regimens for metastatic kidney cancer 2 3 :
Patients received either standard treatment (nivolumab + ipilimumab) or standard treatment plus CBM588 2
Patients received either standard treatment (cabozantinib + nivolumab) or standard treatment plus CBM588 3
| Trial Identifier | Standard Treatment | Experimental Arm | Number of Patients | Primary Endpoint |
|---|---|---|---|---|
| NCT03829111 | Nivolumab + Ipilimumab | + CBM588 | 58 total | Bifidobacterium abundance |
| NCT05122546 | Cabozantinib + Nivolumab | + CBM588 | 30 total | Bifidobacterium abundance |
The studies included patients with histologically confirmed metastatic renal cell carcinoma who had not received prior systemic therapy for their advanced disease 3 . Participants had varying risk profiles according to the International mRCC Database Consortium (IMDC) criteria, with the majority having intermediate or poor-risk disease 3 .
Patients were randomized to receive either standard treatment alone or standard treatment plus CBM588. The researchers collected stool samples from all participants at baseline and after 12-13 weeks of treatment 2 3 . These samples underwent metagenomic sequencing—a sophisticated DNA analysis technique that identifies the types and quantities of bacteria present in the gut 3 .
The variety of bacterial species within each sample
The differences in microbial communities between samples
Changes in particular bacterial species known to be associated with treatment response
While the primary endpoint of increasing Bifidobacterium abundance wasn't met in either trial, CBM588 administration led to other significant microbial changes 2 3 :
Patients receiving CBM588 maintained levels of Eubacterium siraeum—a species repeatedly associated with better response to immune checkpoint inhibitors in melanoma and other cancers 2 . In contrast, those receiving standard treatment alone showed a significant decrease in this important bacterium.
The CBM588 arms showed a decrease in this ratio from 100% at baseline to 75.7% at 12 weeks, suggesting a shift toward a more balanced microbiome signature 2 . The standard treatment group maintained a nearly unchanged ratio (89.0% to 96.4%).
The most exciting findings came from the clinical results:
| Outcome Measure | Standard Treatment (n=10) | CBM588 Group (n=19) | P Value |
|---|---|---|---|
| Objective Response Rate | 20% (2 patients) | 74% (14 patients) | 0.01 |
| 6-Month Progression-Free Survival | 60% (6 patients) | 84% (16 patients) | Not reported |
| Significant Toxicity | Comparable to known safety profile | No significant difference | Not significant |
| Bacterial Species | Change in Standard Care Group | Change in CBM588 Group | Clinical Significance |
|---|---|---|---|
| Eubacterium siraeum | Significant decrease (log fold change: -1.75) | Maintained | Associated with better ICI response |
| Bifidobacterium spp. | No significant difference | No significant difference | Primary endpoint not met |
| Firmicutes/Bacteroidetes ratio | Remained stable (89.0% to 96.4%) | Decreased (100% to 75.7%) | Shift toward more balanced microbiome |
Understanding how scientists study the microbiome helps appreciate the complexity of this research. Here are the key tools and techniques used in these groundbreaking studies:
The compelling results from these initial trials have paved the way for further investigation. As Dr. Nazli Dizman, a researcher involved in these studies, noted: "A phase 3 study is planned within the cooperative groups to evaluate the clinical activity and gut microbiome modulation capacity of CBM588 in combination with ICIs in mRCC" 2 .
Dr. Dizman encourages patients to "participate in studies looking at lifestyle interventions, biotherapeutics, or even FMT, which, so far, has very strong proof-of-concept evidence" .
The research exploring CBM588's impact on the gut microbiome of kidney cancer patients represents a fascinating convergence of microbiology, immunology, and oncology. While much remains to be understood about the precise mechanisms through which our gut bacteria influence cancer treatment outcomes, these studies provide compelling evidence that modifying the microbiome can potentially enhance the effectiveness of existing therapies.
As this field advances, we may be heading toward a future where cancer treatment plans routinely include personalized microbiome modulation strategies—whether through specific bacterial supplements, dietary recommendations, or other approaches—to give patients the best possible chance of overcoming their disease.