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Gut Microbiome, CAR-T, Myeloma
Can the gut microbiome influence CAR-T therapy for myeloma? According to the study linked below, bacterial diversity in your gut enhances your response to CAR-T therapy.
This finding really shouldn’t be a surprise. The gut microbiome influences many aspects of cancer.
How changes in the gut microbiome may impact patient response to CAR-T therapy
How many aspects of cancer are influenced by the cancer patient’s gut microbiome?
The gut microbiome plays a significant and multifaceted role in cancer. Research has shown that the microbiome can influence at least five major aspects of cancer in a patient:
1. Cancer Development (Carcinogenesis)
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Certain microbial species can produce toxins, inflammatory molecules, or metabolites that promote DNA damage, chronic inflammation, and oncogenesis.
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Example: Fusobacterium nucleatum is associated with colorectal cancer due to its pro-inflammatory and pro-oncogenic activity.
2. Tumor Progression and Metastasis
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The microbiome can modulate immune responses and alter the tumor microenvironment, promoting or inhibiting tumor growth and spread.
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Microbial products like short-chain fatty acids (SCFAs) or bile acid metabolites can affect cancer cell behavior.
3. Response to Cancer Therapy
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Chemotherapy: The gut microbiome affects drug metabolism and toxicity. For instance, Enterococcus hirae and Barnesiella intestinihominis enhance the efficacy of cyclophosphamide.
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Immunotherapy: Response to immune checkpoint inhibitors (e.g., anti-PD-1) is influenced by gut microbiome composition—patients with beneficial microbes like Akkermansia muciniphila show better responses.
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Radiotherapy: Gut dysbiosis can worsen side effects and reduce treatment efficacy.
4. Toxicity and Side Effects of Treatment
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Microbial metabolism can produce compounds that either protect against or exacerbate treatment-related toxicities.
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Example: Irinotecan-induced diarrhea is worsened by bacterial β-glucuronidase activity.
5. Prognosis and Survival
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The microbiome can be a biomarker for prognosis. Certain microbial profiles are associated with longer survival or reduced relapse.
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Fecal microbiota composition can predict disease-free survival in some cancers.
Emerging and Related Aspects
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Microbiome-based therapies: Fecal microbiota transplantation (FMT), probiotics, and prebiotics are being investigated as adjuncts to improve cancer treatment outcomes.
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Nutritional modulation: Diet-induced microbiome changes can affect cancer risk and treatment.
Summary
At least five key aspects of cancer—development, progression, therapy response, side effects, and prognosis—are influenced by the gut microbiome. Ongoing research continues to uncover even more complex interactions, suggesting that the microbiome is a critical factor in personalized oncology.
I am a long-term myeloma survivor. Are you a multiple myeloma survivor? Are you considering CAR-T cell therapy? Email me at David.PeopleBeatingCancer@gmail.com with your questions about both conventional and non-conventional therapies.
Good luck,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
Longitudinal analysis of gut microbiome and metabolome correlates of response and toxicity with idecabtagene vicleucel
Key Points
- Major microbiome disruption was associated with toxicities following ide-cel administration in patients with multiple myeloma.
- Bacterial diversity decreased post-ide-cel infusion and bacterial composition was associated with ide-cel response and toxicities.
- Flavonifractor plautii,
- Bacteroides thetaiotaomicron,
- Blautia fecis,
- and Dysosmobacter species
in ide-cel responders. A notable finding was the link between major microbiome disruption, defined as dominant specific taxa (greater than 35% prevalence) and increased facultative pathobionts like Enterococcus, with ide-cel toxicities, especially cytokine release syndrome (CRS).
Patients with genus dominance in baseline samples had a higher incidence of grade 2 or higher CRS at 46.2% compared to those without genus dominance (11.1%, p=0.043).
Additionally, network analysis and mass spectrometric assessment of stool metabolites revealed important associations and pathways, such as Flavonifractor plautii being linked to increased indole metabolites and pathways in responders.
Our findings uncover novel microbiome associations between ide-cel responses and toxicities that may be useful for developing modalities to improve CAR-T outcomes.
gut microbiome CAR-T myeloma gut microbiome CAR-T myeloma gut microbiome CAR-T myeloma