How Your Microbiome Influences Treatment Success
Discover how gut microbiome signatures predict survival outcomes in breast cancer patients receiving eribulin immunotherapy
Imagine that living inside your body right now are trillions of microorganisms—bacteria, viruses, and fungi—that outnumber your own human cells. This complex ecosystem, known as the microbiome, is not just a passive resident but an active player in your health, potentially influencing everything from digestion to cancer treatment outcomes.
Recent groundbreaking research has revealed that the composition of these microscopic communities, particularly those in our gut, may hold the key to understanding why some patients with hormone receptor-positive metastatic breast cancer respond better to certain treatments than others.
The human microbiome consists of diverse communities of microorganisms inhabiting various parts of our bodies, with the most extensive and influential population residing in our gastrointestinal tract. Think of it as a complex metropolis of microbial life, where different species perform specialized functions, communicate with each other, and interact with our human systems.
These microorganisms aren't just hitchhikers; they've evolved with us over millennia, forming symbiotic relationships that benefit both microbes and host 2 7 .
Gut microbes help educate and train our immune cells
Bacteria produce compounds that affect distant tissues
Microbes influence hormone metabolism
Gut-brain axis allows bidirectional communication
For hormone receptor-positive breast cancer—which constitutes approximately 70% of all breast cancers—the relationship between gut microbes and estrogen metabolism is particularly significant.
The estrobolome refers to the collection of bacterial genes capable of metabolizing estrogens. These bacteria produce an enzyme called β-glucuronidase that deconjugates estrogen compounds, allowing them to be reabsorbed into the bloodstream instead of being excreted 6 .
Beyond hormone metabolism, gut microbes shape the tumor microenvironment through immunomodulatory effects. Certain bacterial species can stimulate the activity of CD8+ T cells and other immune cells that attack tumors, while others may suppress these beneficial responses 2 7 .
This immunomodulatory capacity becomes particularly important in the context of immunotherapy, where the goal is to unleash the body's own defenses against cancer.
The research connecting gut microbiome signatures to treatment response emerged from an exploratory analysis of the KELLY phase II study (NCT03222856), which investigated a novel combination therapy for advanced breast cancer 1 3 .
The trial enrolled patients with hormone receptor-positive/HER2-negative metastatic breast cancer who had received prior treatments—a population with limited therapeutic options and generally poor outcomes.
The CALADRIO study was an exploratory retrospective analysis nested within the KELLY trial that aimed to profile both the oral and gut microbiota of a subset of participants.
Twenty-eight consenting patients provided fecal and saliva samples at multiple time points: before treatment began (baseline), after three treatment cycles, and at the end of treatment 1 3 .
Patients Enrolled:
88 randomized
Treatment Arms:
Eribulin alone vs Eribulin + Pembrolizumab
Microbiome Samples:
58 fecal + 67 saliva samples collected
Patients in the CALADRIO study provided fecal samples using standardized protocols from the International Human Microbiome Standard guidelines to ensure consistency and reliability 1 . These samples were stored in DNA preservation buffers to prevent degradation until analysis.
Saliva samples (5 mL each) were collected into sterile containers, aliquoted, and stored at -80°C until processing. For DNA extraction, 2 mL of each saliva sample was centrifuged, and the pellet was resuspended in a bead solution before using specialized kits to extract bacterial DNA 1 .
The researchers used two complementary approaches:
After sequencing, sophisticated bioinformatics tools were employed to process the massive datasets. For the 16S rRNA data, researchers used QIIME v1.9.1 to group sequences into operational taxonomic units (OTUs). For metagenomic data, they used tools like KneadData to remove human DNA sequences 1 .
The final step involved linking microbial features to clinical outcomes. Researchers used statistical approaches to identify which microorganisms were more abundant in patients who experienced clinical benefit compared to those with no clinical benefit 1 .
| Microbial Feature | Location | Association with Outcome | Potential Mechanism |
|---|---|---|---|
| Bacteroides fragilis | Gut | Improved clinical benefit | Induces cancer cell death via microbial metabolites |
| Streptococcus spp. (≥30%) | Oral cavity | Improved clinical benefit | Unknown; may modulate systemic immunity |
| Faecalibacterium | Gut | Dominant genus; possible beneficial role | Produces anti-inflammatory short-chain fatty acids |
| Prevotella | Gut and Oral | Present in both sites; possible interaction | May facilitate gut-oral axis communication |
| Reagent/Material | Function in Research | Application in This Study |
|---|---|---|
| DNA Preservation Buffer | Stabilizes genetic material for accurate analysis | Preserved fecal samples during storage and transport |
| QIAamp PowerFecal Kit | Extracts microbial DNA from complex samples | Isolated bacterial DNA from fecal samples |
| Promega Maxwell RSC PureFood GMO and Authentication Kit | Extracts DNA from food and environmental samples | Processed and quantified DNA from fecal samples |
| PowerSoil Bead Solution | Breaks down tough microbial cell walls | Used in initial processing of saliva samples |
| NovoSeq Platform | High-throughput DNA sequencing | Performed shotgun metagenomic sequencing |
The most immediate application of these findings is the potential development of microbiome-based biomarkers to predict treatment response. If validated in larger studies, testing for specific bacteria like B. fragilis or high oral Streptococcus abundance could help oncologists select patients most likely to benefit from eribulin-based therapies 1 2 .
Specific beneficial bacteria could be administered as live biotherapeutic products to enhance treatment response.
Nutrients that selectively promote the growth of beneficial bacteria could be provided to shape the microbiome.
Transferring stool from responsive patients to non-responders might improve outcomes through microbial community transfer.
Isolated bacterial products with anti-cancer effects could be developed as targeted drugs.
The discovery that gut microbiome signatures can predict survival in patients with hormone receptor-positive metastatic breast cancer receiving eribulin with or without pembrolizumab represents a paradigm shift in oncology.
It suggests that successful cancer treatment depends not only on targeting cancer cells directly but also on nurturing the trillions of microbial partners that share our bodies and influence our health.
While more research is needed to validate these findings and translate them into clinical practice, the message is clear: the future of cancer therapy may involve not just advanced drugs and technologies but also a deeper understanding of our internal microbial ecosystem. As we learn to cultivate this inner garden, we may discover powerful new ways to fight cancer—by harnessing the healing power of our smallest companions.