Nature Immunology, Published online: 30 January 2026; doi:10.1038/s41590-026-02442-5
Publisher Correction: Lymphotoxin-dependent elevated meningeal CXCL13:BAFF ratios drive gray matter injury
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A team at the Johns Hopkins Kimmel Cancer Center and the Bloomberg~Kimmel Institute for Cancer Immunotherapy reports that a mouth-dwelling bacterium tied to periodontal disease could help set breast cancer in motion and make it more aggressive. In their experiments, the microbe appeared to injure DNA and push breast cells toward behaviors linked with cancer growth and spread.
The work, published in Cell Communication and Signaling, focuses on Fusobacterium nucleatum. This bacterium has previously been associated with colorectal and other cancers, and the new study suggests it may also reach the breast. The researchers found evidence that it can enter the bloodstream, settle in breast tissue, and spark inflammation along with other changes that can precede cancer.
Dipali Sharma, Ph.D., a professor of oncology and a John Fetting Fund for Breast Cancer Prevention investigator, led the study. Her team observed that the bacterium sped up tumor growth and made it easier for cancer cells to spread from the breast to the lung in animal models designed to mimic human breast cancer.
“The key takeaway is that this oral microbe can reside in breast tissue and that there is a connection between this pathogen and breast cancer,” says Sharma, adding that the team’s study was inspired by many small studies that looked at thousands of patients and connected periodontal disease to breast cancer.
“We wanted to dig deeper and see if we could uncover the underlying connections,” says Sheetal Parida, Ph.D., first author and a research associate working with Sharma.
To probe how the bacterium might influence the earliest steps of disease, the researchers combined mouse experiments with tests in human breast cancer cells. When F. nucleatum was introduced directly into the breast duct area in mice, the tissue developed metaplastic and hyperplastic lesions, which are noncancerous changes that reflect abnormal growth or shifts in cell identity. These lesions appeared alongside inflammation, signs of DNA damage, and increased cell growth, a pattern consistent with conditions that can raise cancer risk.
When introduced into the bloodstream, the bacterium significantly accelerated the growth and spread of established breast tumors.
The researchers also identified a molecular mechanism underlying these effects. Exposure to F. nucleatum caused DNA damage to cells and activated repair pathways that can introduce mistakes, including nonhomologous end joining, a fast but error-prone way that cells repair broken DNA by directly connecting the broken ends back together.
The researchers found that even brief exposure to the bacterium initiated increased expression of a protein called PKcs that was associated with enhanced tumor cell migration, invasion, stem-like behavior, and resistance to chemotherapy.
The researchers also found that epithelial cells (the cells that line the breast ducts) and breast cancer cells with BRCA1 mutations were particularly vulnerable. BRCA1-mutant cells showed higher levels of a surface sugar (Gal-GalNAc) that helps bacteria bind to and enter a cell. Breast cells with BRCA-1 gene mutations showed increased uptake and long-term retention of F. nucleatum, even across multiple generations of cells, amplifying DNA damage and tumor-promoting effects.
“Our findings reveal a link between oral microbes and breast cancer risk and progression, particularly in genetically susceptible individuals,” says Sharma. “Nothing happens in isolation. The results suggest that multiple risk factors come together with F. nucleatum acting as an environmental factor that may cooperate with inherited BRCA1 mutations to promote breast cancer and tumor aggressiveness.”
She says further studies are needed to explore the clinical implications of these findings, and whether oral health should be considered a risk factor for breast cancer.
Reference: “A pro-carcinogenic oral microbe internalized by breast cancer cells promotes mammary tumorigenesis” by Sheetal Parida, Deeptashree Nandi, Deepak Verma, Mingyang Yi, Ashutosh Yende, Jessica Queen, Kathleen L. Gabrielson, Cynthia L. Sears and Dipali Sharma, 15 January 2026, Cell Communication and Signaling.
DOI: 10.1186/s12964-025-02635-9
The research was funded by the Breast Cancer Research Foundation, Congressionally Directed Medical Research Programs Department of Defense Breast Cancer Research Program grants BC191572 and BC210668), the John Fetting Fund for Breast Cancer Prevention, and the Bloomberg~Kimmel Institute for Cancer Immunotherapy.
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A study finds that oral–gut translocation of collagenase-producing bacteria underpins the well-known association between microbiome perturbations and advanced chronic liver disease (ACLD) in humans. Importantly, Jin et al. detected oral microbial dysbiosis even in patients with compensated ACLD, and both oral and faecal dysbiosis worsened with the stage of liver disease, suggesting that oral dysbiosis precedes similar changes in the gut.
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