The long-held understanding of cancer causation has historically focused on genetic mutations and environmental toxins, but a growing body of evidence points to an unexpected biological culprit: bacteria. While the link between cancer and bacteria is not as ubiquitous as with viruses, certain bacterial species are now formally recognized as carcinogens. This connection is primarily driven by chronic infection and the collective community of microbes, known as the microbiome. Understanding this microbial influence is reshaping how researchers approach cancer prevention, diagnosis, and treatment.
Established Bacterial Links to Cancer
The most recognized and well-studied bacterial carcinogen is the spiral-shaped microbe Helicobacter pylori, which colonizes the stomach lining. Persistent infection with H. pylori is strongly associated with approximately 70% of all gastric cancer cases worldwide, making it a major contributor to this malignancy. The bacterium also causes nearly all cases of mucosa-associated lymphoid tissue (MALT) lymphoma, a cancer arising in the stomach. For patients diagnosed with early-stage MALT lymphoma, eliminating the H. pylori infection using a course of antibiotics can often lead to complete remission of the cancer.
Beyond the stomach, other bacteria are implicated in cancers of the digestive tract, particularly colorectal cancer (CRC). The oral bacterium Fusobacterium nucleatum is frequently found enriched within CRC tumor tissue. Its presence is associated with a poorer prognosis for patients. Other species, such as certain toxigenic strains of Escherichia coli and Streptococcus gallolyticus, have been linked to an increased risk of colorectal cancer.
Mechanisms: How Bacteria Promote Tumor Growth
The carcinogenic effect of bacteria is exerted through two primary cellular pathways: the induction of long-term inflammation and the direct damage caused by bacterial toxins. Chronic inflammation, regardless of its initial cause, creates a pro-tumor microenvironment that favors uncontrolled cell growth. Persistent bacterial presence recruits immune cells like neutrophils and macrophages to the infection site, which in turn release high levels of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS). These highly reactive molecules are intended to kill the invaders but also cause oxidative stress that damages the DNA of the host cells, leading to mutations and genomic instability.
Alongside this inflammatory process, many pathogenic bacteria produce compounds that directly interfere with host cell function. For instance, the H. pylori virulence factor Cytotoxin-associated gene A (CagA) is injected into gastric cells via the Type IV Secretion System. Once inside, CagA hijacks and disrupts multiple host signaling pathways, including those that control cell growth and survival. CagA also impairs the host cell’s ability to repair damaged DNA, accelerating the accumulation of cancer-promoting mutations.
Other microbes contribute to cancer through the production of potent genotoxins. Certain strains of E. coli harbor a gene cluster that allows them to produce a genotoxin called colibactin. Colibactin can enter host cells and chemically modify (alkylate) the DNA, causing double-strand breaks. If the host cell survives this damage, the resulting genomic instability can drive the cell toward malignant transformation.
The Broader Impact of the Microbiome
The influence of bacteria on cancer extends far beyond single pathogenic species to the entire community of microbes residing in the body, primarily in the gut, known as the microbiome. A state of microbial imbalance, termed dysbiosis, is frequently observed in cancer patients and can create an environment conducive to tumor development. The protective function of a healthy, diverse microbiome centers on the fermentation of dietary fiber, which produces beneficial metabolites called Short-Chain Fatty Acids (SCFAs), such as butyrate.
Butyrate serves as the primary energy source for the cells lining the colon, helping to maintain the integrity of the intestinal barrier and reduce inflammation. In a healthy colon, butyrate acts as a tumor suppressor by inducing programmed cell death in abnormal cells and inhibiting the inflammatory NF-κB signaling pathway. When the microbiome is imbalanced, SCFA production is diminished, leading to increased inflammation and a higher risk of colorectal cancer.
The composition of the gut microbiome also plays a substantial role in determining the effectiveness of modern cancer treatments, particularly immune checkpoint inhibitors (ICIs). Patients with a more diverse microbial profile, often characterized by the presence of bacteria like Akkermansia muciniphila and Bifidobacterium, show better responses to ICIs. Conversely, antibiotic use, which disrupts the gut community, is associated with a poor response to these immunotherapies. This suggests that the gut flora can enhance the anti-tumor immune response by promoting the function of tumor-fighting CD8+ T cells.
Prevention and Therapeutic Strategies
The established link between bacteria and cancer provides direct targets for prevention and intervention. The most straightforward approach is the eradication of established pathogenic infections, such as using antibiotics to clear H. pylori infection to prevent gastric cancer and treat MALT lymphoma. For other bacteria, a focus is on dietary modulation to support a protective microbiome. A diet rich in high-fiber foods feeds the beneficial bacteria necessary for robust SCFA production. This dietary approach helps to maintain a healthy gut barrier and reduces the inflammation that can otherwise drive tumor growth.
The therapeutic potential of the microbiome is now being explored through targeted microbial interventions. Researchers are investigating the use of probiotics containing SCFA-producing or immune-boosting strains to improve cancer outcomes. Fecal Microbiota Transplantation (FMT), which involves transferring the microbial community from a healthy donor to a patient, has shown promise in reversing resistance to immunotherapy. Furthermore, beneficial microbial metabolites, such as butyrate, are being studied as potential therapeutic agents to directly suppress tumor growth or enhance the effects of chemotherapy and immunotherapy.