For decades, cancer treatment has followed a relatively straightforward path: surgery, radiation, chemotherapy, and more recently, immunotherapy. But in recent years, scientists have begun to uncover a powerful influencer that operates quietly behind the scenes, our gut microbiota.

While it might seem strange that gut microbes could influence the outcomes of lung cancer treatment, the role of our gut microbiome in a wide array of illnesses and routine physiological processes throughout the body is becoming ever clearer. The gut is home to trillions of bacteria that help us digest food, regulate immune responses, and even produce essential nutrients. But these microbes also play a role in how our bodies respond to illness, including cancer.

Previous research has shown that the gut microbiome can influence the success of immunotherapy, a type of cancer treatment that harnesses the body’s immune system to attack tumors. What makes Prof. Facciabene’s study unique is its focus on how the microbiome might interact with radiation therapy, particularly for patients who aren’t eligible for surgery.

The study focused on patients with early-stage non-small cell lung cancer who couldn’t undergo surgery and were instead treated with stereotactic body radiotherapy (or SBRT for short), a highly precise form of radiation therapy. These patients were randomly divided into two groups. One group received SBRT alone, while the other also took oral vancomycin, a well-known antibiotic that doesn’t leave the gut.

Why vancomycin? Unlike antibiotics that spread throughout the body and often harm helpful bacteria, vancomycin stays in the gut and selectively targets certain bacteria, mostly gram-positive ones. This means that it can shift the balance of the microbiome without broadly disrupting it.

Over five weeks, the researchers tracked not just the safety and tolerability of this combination but also a wide array of biological changes, from immune cell activity to shifts in the molecular byproducts of metabolism.

The results were striking. Patients who received vancomycin along with SBRT had significantly better progression-free and overall survival rates than those who received SBRT alone. In other words, their cancer was less likely to return, and they were more likely to live longer.

Even more fascinating were the biological changes under the microscope. Vancomycin led to a dramatic restructuring of the gut microbiota. Certain bacteria known to dampen immune responses were reduced, while others that promote immune activity became more dominant. This shift was accompanied by a drop in short-chain fatty acids, which normally help reduce inflammation. Paradoxically, lowering these anti-inflammatory compounds seemed to help the immune system stay on high alert, ready to fight cancer cells.

The immune system responded to these microbial changes. Dendritic cells and T cells, key players in identifying and attacking tumors, became more active. Blood tests showed that genes responsible for presenting antigens (tiny flags that tell immune cells what to attack) were more highly expressed. In essence, the body’s cancer-fighting machinery was turned up a notch.

The implications of this work are profound. First, it challenges a longstanding assumption that antibiotics always hurt cancer patients by weakening the immune system. Prof. Facciabene’s team showed that when used thoughtfully, some antibiotics might do the opposite.

Second, it points toward a more personalized, nuanced approach to cancer treatment. Rather than seeing the gut microbiome as a passive bystander, this research positions it as an active player, one that can be manipulated to make traditional therapies more effective.

Third, and perhaps most importantly for patients, this strategy uses a low-cost, well-understood medication with minimal side effects. The worst reported outcomes were mild gastrointestinal discomfort, nothing compared to the harsh side effects of many cancer drugs, such as classic chemotherapies.

Excitingly, this research is just the beginning. The study shows that the gut microbiome can be strategically targeted, not just preserved, to help the immune system recognize and destroy cancer. The results give us a foundation to explore similar interventions in other cancers and therapies.

The researchers have advocated for larger clinical trials to validate these findings and explore how gut-targeted antibiotics might synergize with other treatments, including immunotherapy. As with any pilot study, there are limitations. The study involved a small number of patients and was partially affected by disruptions from the COVID-19 pandemic. But even with these hurdles, the results are promising and warrant further investigation.

We’re entering an era where treating cancer doesn’t have to mean adding more toxicity to the body. It might mean rethinking the battlefield altogether and arming the immune system with help from an unlikely ally: the bacteria in our guts.

In the future, a course of antibiotics such as vancomycin could be prescribed not to fight infection, but to improve the body’s own ability to fight cancer. If this line of research continues to bear fruit, we’ll owe part of that progress to the curiosity and tenacity of scientists such as Prof. Andrea Facciabene, who are willing to look at old drugs in new ways, and see the potential where few thought to look.