Bacterial Signatures in Prostate Tissue Linked to Cancer in Landmark French Study

For decades, the prostate was assumed to be a sterile organ, shielded from the microbial world that populates the gut, the skin, and the mouth. That assumption has now collapsed. A large French clinical trial known as MICROPROSTK has delivered the most detailed portrait yet of the bacteria living inside prostate tissue, and its findings point to a provocative possibility: men with prostate cancer carry a measurably different microbial community in their prostates than men whose biopsies come back clean. The study, conducted across six tertiary care hospitals between February 2021 and June 2023, enrolled 296 patients and ultimately analyzed 235, combining prostate biopsies, urine samples, and rectal swabs from each participant. Using cutting-edge full-length 16S rDNA sequencing on the PacBio Sequel II HiFi platform, the researchers achieved something earlier efforts could not: species-level identification of the bacteria residing in one of the most inaccessible organs in the male body.

The technical leap matters enormously. Most previous studies of the prostate microbiome relied on short-read sequencing of the 16S ribosomal DNA gene, a workhorse method that can reliably identify bacteria only down to the genus level. Because closely related species within a genus can behave very differently in the body, that resolution limit left researchers guessing about which specific organisms might matter. By sequencing the full-length 16S gene and processing the reads into amplicon sequence variants, or ASVs, the MICROPROSTK team could distinguish individual species with far greater confidence. The payoff was a catalog of remarkable breadth: across prostate biopsy samples alone, the researchers identified 22 phyla, 31 classes, 83 orders, 158 families, 330 genera, and 959 species. In total, 11,922 ASVs were characterized in prostate tissue, alongside 3,741 in urine and 15,424 in rectal samples.

The cohort itself was designed to reflect real clinical practice. All participants were men with a clinical suspicion of prostate cancer, triggered by an abnormal digital rectal examination, elevated prostate-specific antigen, or suspicious findings on magnetic resonance imaging. After excluding patients who had recently taken antibiotics, dropped out, or deviated from the protocol, the final analysis included 122 men with biopsy-confirmed prostate cancer and 113 without malignancy. In the subgroup with adequate DNA yield from all three sample types, 72 cancer patients were compared against 69 controls. The two groups were broadly similar, though cancer patients were slightly older, with a mean age of 70.0 versus 67.0 years, and had higher comorbidity scores. Notably, PSA levels did not differ significantly between the groups, underscoring the well-known limitations of that blood test and the need for complementary biomarkers.

Because prostate biopsies yield very little tissue, and therefore very little DNA, the researchers took extraordinary precautions against contamination, a notorious pitfall in low-biomass microbiome studies. Sampling procedures were standardized across all six centers, DNA extraction and sequencing followed uniform protocols, and a blank control was included in every extraction batch to monitor for stray genetic material. Stringent quality filtering and bioinformatic processing were then applied to reduce the impact of potential contaminants. Even so, the authors acknowledge that low-level residual contamination cannot be entirely excluded in studies of this kind, a caveat that applies to virtually all tissue microbiome research and one they weigh carefully in interpreting their results.

The headline finding concerns diversity. In prostate biopsies, both species richness and Shannon diversity, a standard metric that combines the number of species with how evenly they are distributed, were significantly higher in men with prostate cancer than in those without, with p-values of 0.046 and 0.019 respectively. No significant differences emerged in urine or rectal samples, although both diversity indices trended higher in cancer patients across all sample types. Intriguingly, beta diversity analyses, which assess whether whole microbial communities differ in composition, showed no significant separation between cancer and non-cancer patients in any sample type. But the beta diversity comparisons did confirm something else important: the prostate, urine, and rectum each harbor clearly distinct microbial communities, reinforcing the idea that the prostate hosts its own resident ecosystem rather than merely collecting bacteria drifting in from neighboring sites.

When the researchers drilled down to which bacteria were actually enriched in cancerous tissue, a distinctive pattern emerged. At the phylum level, Synergistota stood out as significantly more abundant in prostate cancer patients. At the genus level, Bacteroides, Agathobacter, Ruminococcus, Cutibacterium, and Lachnoclostridium were enriched in cancer tissue, while Chryseobacterium was more abundant in non-cancer samples. The species-level results were even more striking: Eubacterium rectale, Cutibacterium acnes, Bacteroides dorei, Ruminococcus torques, Bacteroides massiliensis, Ruminococcus lactaris, Eubacterium halii, Bilophila wadsworthia, Clostridium disporicum, and Clostridium spiroforme were all significantly enriched in prostate cancer patients. Five of these species, E. rectale, C. acnes, B. dorei, L. reuteri, and R. torques, showed mean relative abundances above one percent in at least one of the two groups, marking them as the strongest candidates for future validation.

Some of these organisms carry compelling biological backstories. Cutibacterium acnes, formerly known as Propionibacterium acnes, has been repeatedly detected in prostate tissue in prior studies and is known to provoke chronic inflammation and modulate immune responses. Mouse models using human prostate cancer-derived isolates of the bacterium have induced chronic prostatic inflammation, and laboratory work suggests the organism can induce immunosuppressive gene expression in macrophages and even invade prostate epithelial cells. Eubacterium rectale, meanwhile, has been implicated in inflammation-related colorectal carcinogenesis, raising the speculative but tantalizing question of whether similar mechanisms could operate in the prostate. On the protective side of the ledger, Lactobacillus reuteri was significantly more abundant in the non-cancer group, and this species has documented anti-inflammatory properties, including the production of reuterin, a compound shown in other work to suppress colorectal cancer growth by altering redox balance in cells.

The study’s design carries inherent limitations that the authors confront directly. Every participant received a single oral dose of the antibiotic ciprofloxacin two hours before biopsy as standard prophylaxis, a uniform exposure across both groups that may nonetheless have altered microbial composition. Because taking prostate biopsies from healthy men is not ethically justifiable, the comparison group consisted of men biopsied for suspected cancer whose histology showed no malignancy, a clinically relevant but imperfect control group that included some patients with prostatitis or benign prostatic abnormalities. The predominance of low-grade tumors, with ISUP grade 1 accounting for roughly 41 percent of cancers, means the findings mainly reflect early-stage disease, which is ideal for biomarker discovery but may not extend to aggressive cancers. And because the study was cross-sectional, capturing a single moment in time, it cannot determine whether the observed microbial differences contribute to cancer development or merely accompany it.

What comes next could determine whether this research translates into clinical tools. The team proposes validating the bacterial signatures with species-specific quantitative PCR and culturomics on prostate tissue, then extending the search to urine and rectal samples, specimens that can be collected without a needle in the prostate. If microbial signatures reliably detectable in urine track with the tissue findings, the door opens to non-invasive screening tests that could complement PSA, MRI, and biopsy. Functional studies in laboratory and animal models will then be needed to establish whether the enriched bacteria actively drive tumorigenesis or simply flourish in the altered environment of a tumor. Prostate cancer remains the second most frequently diagnosed cancer in men worldwide and the fifth leading cause of cancer death, with an estimated 473,011 new cases and 115,182 deaths in Europe alone in 2022. No specific prevention strategy can currently be recommended, and existing treatments, however effective, often compromise sexual function and quality of life. Against that backdrop, the idea that a handful of bacterial species, some potentially targetable with antibiotics, probiotics, or other interventions, might influence prostate cancer risk represents one of the most consequential open questions in urological oncology today.

Subject of Research: Prostate tissue microbiota dysbiosis and its association with prostate cancer

Article Title: Prostate tissue microbiota dysbiosis associated with prostate cancer: results from the MICROPROSTK multicenter study

Article References: Lotte, R., Gaudart, A., Cruzel, C., Droupy, S., Lavigne, J., Bruyère, F., Lanotte, P., Lechevallier, E., Dubourg, G., Fournier, P., Haider, R., Lotte, L., Youssef, K., Emery, A., Madany, R., Payen, M., Pfauwadel, L., Tibi, B., Ahallal, Y., … Ruimy, R. (2026). Prostate tissue microbiota dysbiosis associated with prostate cancer: results from the MICROPROSTK multicenter study. New Microbes and New Infections, Article 101862. https://doi.org/10.1016/j.nmni.2026.101862

Image Credits: AI Generated

DOI: 10.1016/j.nmni.2026.101862

Keywords: prostate cancer, microbiota, dysbiosis, 16S rDNA sequencing, Cutibacterium acnes, Eubacterium rectale, Lactobacillus reuteri, MICROPROSTK, biomarkers, urinary microbiome, inflammation, multicenter study