Cancer and the Gut Microbiome: What’s the Latest Research?
The gut microbiome – an intricate community of trillions of bacteria, fungi and other microorganisms – has emerged as a central focus in cancer research. Once thought of mainly as a digestive aid, it is now recognized as a powerful regulator of immunity, inflammation and metabolism, all of which are tightly linked to cancer biology.
When this ecosystem falls out of balance, a state known as dysbiosis, harmful microbes can disrupt immune signaling and weaken the intestinal barrier. Such changes have been connected to the development of colorectal, liver and breast cancers by fueling inflammation, generating carcinogenic compounds and creating conditions that favor tumor growth.
Growing evidence suggests that decoding the interplay between the microbiome and cancer could transform prevention, diagnosis and treatment. By mapping microbial patterns tied to disease risk, researchers aim to uncover biomarkers and design interventions that restore a healthier balance.
In a recent Technology Networks miniseries, we explored how the microbiome shapes cancer therapies, the role of diet and how bacteria themselves can be engineered to fight cancer. This article distills the key take-home messages from those discussions.
How the microbiome shapes cancer therapy effectiveness
The microbiome not only influences cancer risk but also impacts how patients respond to treatment. Evidence has shown that gut microbes affect how chemotherapy and immunotherapy are metabolized, tolerated and ultimately, how effective they are.
Dr. Peter Turnbaugh, professor of microbiology and immunology at UC San Francisco, explained: “Recent research has implicated the microbiome in the metabolism, absorption and even mechanism-of-action of both chemotherapy and immunotherapy. While much of the data comes from cell culture or animal models, compelling associations are now emerging in human patients as well.”
Checkpoint inhibitors, a class of immunotherapy, are especially dependent on the microbiome. Certain microbial communities appear to boost T-cell activity, strengthening the immune system’s ability to detect and destroy tumors. However, dysbiosis can blunt these responses, limiting treatment success. This has prompted new strategies to manipulate the microbiome before treatment – including dietary interventions, antibiotics, probiotics and fecal microbiota transplantation (FMT) – to enhance immunotherapy outcomes.
Chemotherapy also profoundly reshapes the gut microbiome, often reducing its diversity and fostering the overgrowth of pathogenic species. One notable example is Fusobacterium nucleatum, which has been associated with resistance to chemotherapy in colorectal cancer. Researchers found that this bacterium can activate autophagy pathways and immune signaling that promote tumor survival, complicating treatment.
On the other hand, beneficial bacteria may protect patients during chemotherapy. In a recent study led by Turnbaugh’s team, gut microbes surviving fluoropyrimidine chemotherapy metabolized the drug into a harmless byproduct, reducing severe side effects such as nausea and vomiting. The researchers also found that these bacteria could predict patient responses – and when transferred into mice, they alleviated treatment-related toxicity.
Another protective mechanism involves vitamin K2. Turnbaugh’s group observed that chemotherapy-induced expansion of bacterial genes for vitamin K2 synthesis helped shield both microbial and host cells from drug toxicity. These discoveries highlight a paradigm shift: the microbiome is not merely a bystander but an active participant in shaping cancer therapy outcomes.
Diet, the microbiome and cancer development
Diet is one of the most direct and modifiable influences on the microbiome, and by extension, cancer risk. The Western diet, characterized by a high intake of processed meats, refined sugars, saturated fats and ultra-processed foods, is strongly linked to obesity, chronic inflammation and microbiome disruption. These changes are associated with elevated risks of cancers, particularly colorectal cancer (CRC).
The World Health Organization’s International Agency for Research on Cancer classified red and processed meats as probable human carcinogens in 2015. Data shows that eating just 50g of processed meat daily increases CRC risk by 16%, with risk rising further at higher intake. These dietary patterns also seem to enrich microbial species such as Bacteroides, Bilophila and Alistipes, which promote mucosal damage, inflammation and the production of carcinogenic metabolites.
By contrast, diets high in fiber, fruits and vegetables foster microbial communities that produce short-chain fatty acids like butyrate, known for its anti-inflammatory and anti-carcinogenic effects. Still, the relationship between diet, the microbiome and cancer remains complex.
“There is good evidence that specific foods are associated with cancer risk,” Dr. Emily Vogtmann, Earl Stadtman Investigator at the National Cancer Institute, told Technology Networks. “However, the relationship between the gut microbiome and cancer, or how the gut microbiome may mediate associations between diet and cancer, is less well understood.”
Vogtmann emphasized the need for prospective studies that track diet, microbiome changes and cancer development over time, as most existing data are cross-sectional or animal-based. She also highlighted a key nuance: while diet shapes risk at the population level, individual outcomes vary widely. A person eating a poor diet may never develop cancer, while another following a healthy diet may still be diagnosed, underscoring the multifactorial nature of disease.
For now, much of the actionable advice remains rooted in established guidelines: reduce processed meat intake, increase fruits/vegetables/fiber and adopt healthier lifestyle behaviors, such as not smoking and limiting alcohol. Still, future integration of microbiome data may help refine cancer prevention strategies at the individual level.
Engineering the microbiome for cancer therapy
As research deepens, scientists are moving beyond observation to intervention, seeking ways to engineer the microbiome itself for therapeutic benefit.
FMT, already used successfully for recurrent Clostridioides difficile infections, is being investigated in oncology to restore microbial diversity and reprogram the tumor microenvironment toward an anti-tumor state. However, as University of Chicago researchers have pointed out, FMT is best viewed as a proof-of-concept. The approach introduces entire microbial ecosystems, making host-microbe interactions difficult to predict, especially in immunocompromised patients.
Probiotics and prebiotics offer more targeted options. Probiotics have shown potential to reduce postoperative complications in CRC surgery and may support treatment responses with minimal side effects. Yet, their benefits are not without caution: in vulnerable patients, probiotics can occasionally cause infections or contribute to antibiotic resistance.
The frontier of this field lies in synthetic biology. Researchers are engineering “smart” bacteria capable of sensing their environment and delivering therapeutic molecules with precision. In preclinical models, Pediococcus pentosaceus (P. pentosaceus) engineered to secrete a protein called P8 significantly reduced tumor growth in colorectal cancer. Unlike attenuated pathogenic bacteria, lactic acid bacteria such as P. pentosaceus are safe, food-grade strains well-suited for therapeutic delivery.
Other approaches target the tumors directly. Neobe Therapeutics, for example, is developing engineered bacteria designed to infiltrate solid tumors and degrade their fibrotic barriers, which often prevent drugs from penetrating effectively. “Our engineered bacteria act as biological Trojan horses, remodeling tumors from the inside to make them vulnerable to existing drugs,” Dr. Pedro Correa de Sampaio explained to Technology Networks. By exploiting bacteria’s natural tendency to colonize tumors, this strategy aims to turn a challenge into a therapeutic advantage.
The gut microbiome is emerging as both a driver and a target in cancer. From shaping treatment responses to being reshaped by diet and even engineered for therapy, this microbial ecosystem is central to the future of oncology. Harnessing its power could transform cancer prevention, treatment and personalized medicine.
