A session at United European Gastroenterology (UEG) Week 2025 shined a spotlight on the emerging role of the gut microbiome in gastrointestinal (GI) cancer.

From the stomach to the colon, manipulating the gut microbiome may hold the key to prevention, diagnosis, and even treatment of colorectal cancer and other GI malignancies, but only if science, medicine, and technology evolve together, attendees heard.

Beyond Helicobacter pylori: A Broader Microbial Map

In his lecture, Juozas Kupcinskas, MD, PhD, chief of gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania, acknowledged the well-established role of H pylori in gastric cancer but noted that this bacterium cannot be the whole story.

“Regardless of all the research efforts, we don’t understand why only very few individuals infected with H pylori develop gastric cancer. Furthermore, we have patients who do not have H pylori, and they still develop gastric cancer,” Kupcinskas said.

Kupcinskas noted that while H pylori “fulfills all the postulates for the bacteria that can cause cancer,” growing evidence suggests other microbial players may also influence carcinogenesis “because when we do sequencing, we find lots of bacteria.” His team has been probing whether bacteria beyond H pylori adhere to the stomach mucosa and potentially drive inflammation or cancer development.

Diet, Drugs, and the Disrupted Ecosystem

In a separate lecture, Gianluca Ianiro, MD, associate professor of gastroenterology at the Catholic University of Rome, Rome, Italy, noted that the microbiome’s composition is shaped by both genes and the environment, but environmental factors have a much larger influence — meaning it can be modified “for bad and for good.”

Ianiro described modern Western lifestyles as “a disaster for the microbiome,” noting that dietary habits, antibiotic exposure, and sedentary behaviors have collectively eroded microbial diversity — a hallmark of gut health.

“This loss of alpha diversity is seen across virtually all chronic disorders — and cancer is no exception,” Ianiro said. Environmental risk factors linked to colorectal cancer, including smoking, alcohol, aging, and poor diet, all share the common denominator of disrupting microbial balance, he said.

Kupcinskas noted that medications such as proton pump inhibitors and antibiotics can dramatically alter the stomach’s microbial landscape, which may induce “strong inflammation and, in the long run, cancer.”

Ianiro echoed similar concerns for the lower GI tract, highlighting how diets rich in choline and processed fats can drive production of colibactin — a bacterial toxin that can alter DNA and increase the risk for colorectal cancer.

Together, emerging data reinforce that microbial imbalance — or dysbiosis — may be a shared carcinogenic mechanism throughout the GI system, Ianiro said.

Diagnostics and Therapeutic Breakthroughs

The promise of microbiome-driven diagnostics and therapies for GI cancer is growing.

Ianiro noted that stool-based biomarkers are now recommended in colorectal cancer screening guidelines, with various options such as fecal immunochemical test and multi-target stool DNA tests now standard. These tests can detect microbial “signatures” associated with colorectal cancer, offering noninvasive alternatives to colonoscopy for some patients, Ianiro said.

Kupcinskas’ group is developing artificial intelligence-assisted diagnostic tools that combine microbiome, genomic, and imaging data to identify precancerous gastric lesions through the European Union’s Horizon Europe Artificially Intelligent Diagnostic Assistant project.

Therapeutically, Ianiro highlighted the potential of fecal microbiota transplantation (FMT).

Once confined to treating Clostridium difficile infections, early research suggests that FMT can enhance immunotherapy outcomes and mitigate its side effects.

Ianiro cited clinical trials in which FMT alleviated immune-related colitis — a common complication of immune checkpoint inhibitors — and even extended progression-free survival in patients with renal cell carcinoma receiving combined chemo-immunotherapy.

He also pointed to another advance — the TopoScore — a microbial panel developed by researchers at the Gustave Roussy Cancer Institute in Villejuif, France, that predicts a patient’s response to cancer immunotherapy on the ecological topology of their gut microbiome.

Kupcinskas noted similar microbial links to immunotherapy response. In one study from France, Faecalibacterium prausnitzii was associated with a better response to immune checkpoint inhibition in patients with gastric cancer. There have been similar successes in melanoma, where fecal transplants from responders resensitized nonresponders to immunotherapy, he noted.

Toward Clinical Integration — and Standardization

Despite the promise the microbiome holds in GI cancer, both researchers emphasized the need for rigor and standardization going forward.

Kupcinskas warned that microbiome research remains fraught with “technical inconsistencies” across sequencing and sample handling that can lead to unreliable results. He also warned that failing to adjust for confounding factors such as diet, medication, and stool consistency can drastically change results.

Ianiro described the current microbiome research landscape as “chaotic and dysregulated,” with fragmented markets and few structured FMT programs.

“Building an FMT service is tough,” he admitted, citing logistical and educational gaps. “Most clinicians are not trained to be microbial scientists,” which slows adoption of microbiome-based therapies, Ianiro said.

To move forward, Ianiro outlined four key pillars: standardization of methods, rational trial design, integration of basic and clinical science, and improved interdisciplinary communication. These, he said, would form the foundation for safely and effectively incorporating microbial manipulation into clinical care.

Kupcinskas added that large-scale biobanking and collaboration will be essential to bring microbiome-based diagnostics and therapies into clinical practice.

Both experts converged on a vision of iterative, translational science — where discoveries in microbial ecology directly inform patient care. “Starting from clinical observation,” Ianiro said, “we must go back and forth — from correlation to causation, and back to the clinic.”

Kupcinskas agreed. Manipulating the microbiome, he said, remains an exciting but early frontier. “The only way to answer those questions is doing further research.”

Kupcinskas and Ianiro had no relevant disclosures.