Organ microbiome: identification of the endogenous (commensal) 'non-human' component with translational, diagnostic, prognostic, and therapeutic potential

Co PI, Dott.ssa Elda Tagliabue

Microorganisms—including bacteria, viruses, fungi, and protozoa—constitute the human microbiota. The majority of these microbes colonize the gastrointestinal tract, where they play crucial roles in metabolism and immune system regulation. Thanks to advances in high-throughput DNA sequencing technologies, it has become evident that, beyond the gut, several tissues once considered sterile actually harbor symbiotic microbial communities. Notably, tumors themselves host a distinct microbiota that differs from that of healthy tissue. Recent preclinical studies suggest that microbes can influence the tumor microenvironment by modulating immune pathways, producing bioactive metabolites, and directly interacting with host cells, ultimately impacting tumor biology and clinical outcomes. 

In this context, we have initiated a stepwise research approach aimed at identifying specific microbial communities capable of distinguishing early-stage tumors with poor prognosis from those with less aggressive behavior. The cancers’ type under investigation represent the most prevalent and lethal solid malignancies, including: 

• Non-Small Cell Lung Cancer: examining the microbiota in the tumor and in normal lung tissues in relation to disease progression. 
• High-Grade Serous Ovarian Cancer: comparing the microbiota found in peritoneal washings from at-risk healthy women to the microbiota in ascitic fluid from patients with aggressive disease, with the goal of identifying early markers of disease onset and peritoneal dissemination. 
• Breast Cancer: (i) analyzing the tumor microbiota in patients with ductal carcinoma in situ (DCIS) who do or do not progress into invasive cancer, to identify prognostic and management-related microbial markers; (ii) measuring circulating levels of lipopolysaccharides (LPS) as potential predictors of response in intervention studies targeting women with metabolic syndrome, and consequently increased risk of developing breast cancer. 
• Prostate Cancer: investigating the microbiota of normal prostate tissue in patients under active surveillance to identify microbial markers that could help distinguish truly indolent from potentially upgrading tumors. 
• Pseudomyxoma Peritonei: characterizing the microbial communities of the gut, appendix, and peritoneal cavity to explore their involvement in disease dissemination. 

All collected samples have undergone bacterial DNA extraction/enrichment, 16S rRNA gene library preparation, and sequencing of variable regions, with bioinformatic analysis currently in progress. Obtained results are expected to shed light on tumor-associated microbial signatures linked to disease progression, immune modulation, and clinical outcomes. These findings may pave the way for the development of novel biomarkers and microbiome-informed therapeutic strategies, ultimately contributing to more personalized and effective approaches in oncology.