In a compelling ASCO 2025 educational session at a recent oncology conference, Drs. Ariel Elkrief, Jennifer McQuade, and Lawrence Zitvogel delivered a powerful message that’s been gaining traction across immunotherapy circles: what’s happening in the gut may be just as important as what’s happening in the tumor.
Their focus? The profound—and often under-appreciated—impact of the microbiome on immunotherapy outcomes. Specifically, how antibiotics and other medications might undermine our best efforts with immune checkpoint inhibitors (ICIs), and how interventions like fecal microbiota transplantation (FMT) are opening new therapeutic doors.
Antibiotics: A Double-Edged Sword in Cancer Care
Antibiotics are a mainstay in oncology, where patients are immunocompromised and infections are a constant threat. But the overuse—or even just poorly timed use—of antibiotics may come at a steep cost.
In one pivotal study of patients with advanced non-small cell lung cancer, those who received antibiotics near the start of immunotherapy had a median survival of just 7.9 months, compared to 24.6 months for those who didn’t. That’s a striking gap—and not a one-off. Meta-analyses involving 46,000+ patients confirm that antibiotic exposure can significantly reduce both progression-free and overall survival in patients receiving IO. Importantly, these effects were not seen when antibiotics are given alongside chemotherapy or targeted therapy, pointing to a unique vulnerability in immunotherapy.
What’s the Mechanism?
The gut microbiome plays a key role in regulating the immune system. Antibiotics can wipe out beneficial bacteria, leading to a less responsive immune environment. Mouse models show that antibiotic-treated animals have blunted anti-tumor responses. Human data echoes this, suggesting increased immune exhaustion and reduced IO efficacy after microbiome disruption. There’s even emerging evidence that antibiotic use might increase the risk and severity of immune-related side effects.
Not All Microbiome Interventions Are Equal
While it might be tempting to reach for over-the-counter probiotics to “fix” the microbiome, the panel was clear: don’t. There’s no good evidence these products help in the IO setting. In fact, some studies suggest they may actually worsen outcomes!
On the other hand, fecal microbiota transplantation (FMT)—where gut bacteria from a healthy or IO-responsive donor are transplanted into a patient—has shown real promise. In small clinical trials, FMT has helped some patients who were previously resistant to anti-PD-1 therapy start responding again. Response rates in these studies ranged from 20% in PD1-refractory cases to as high as 65% in first-line settings. There’s even early data in lung cancer and renal cell carcinoma suggesting synergistic benefits when FMT is combined with immunotherapy.
Practical Takeaways for Providers
This isn’t just theory—it’s a call to action (detailed review). Providers should:
- Use antibiotics judiciously: Confirm infections, use narrow-spectrum agents, and keep courses short.
- Avoid routine probiotic use: No proven benefit, and potential harm.
- Consider the microbiome in clinical decisions, especially when managing IO patients.
- Collaborate with ID and stewardship teams to minimize collateral damage to the gut.
- Minimize Polypharmacy ie Benzos, PPIs
There’s also growing awareness of other medications—proton pump inhibitors, laxatives, benzodiazepines—that may negatively affect IO efficacy. It’s a reminder that in immunotherapy, polypharmacy matters.
A New Frontier
The future of immunotherapy may lie not just in the drugs we give, but in the ecosystems our patients carry within them. With ongoing trials exploring diet modifications, prebiotics, and next-gen microbiome interventions, we’re just beginning to understand the full impact of the gut on cancer care.
So next time you reach for a prescription pad—or review a medication list—pause and ask: what might this mean for the microbiome?
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. He brings a wealth of expertise to the complex and challenging world of oncology
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