Bladder cancer (BC) is the fourth most prevalent cancer in men and 11th in women. Environmental toxins that enter the body are eventually excreted through kidneys, and they interact with the urinary tract microbiome to generate metabolites that may contribute to the development of BC. Members of the microbiome impact production of HBDs2 and 3 but the production of HBD1 is constitutive and host-specific. As antimicrobial peptides, HBDs 2 and 3 create a feedback loop with the bladder mucosa microbiome in which each controls the steady state of the other. However, in bladder cancer patients host-specific HBD1 production may decrease, which could impact the delicate interplay between human and microbial HBD production, and autonomous defensin production by tumor cells could further alter microbiome-defensin dynamics in the bladder of BC patients. To elucidate microbiome-defensin dynamics in BC patients, the authors sampled mucosal tissue from BC patients, performed histological analysis, measured microbiome-produced defensin levels, and collected urine samples for defensin level quantification. Quantifying HBD levels revealed increases in HBD2 and HBD3, and a decrease in HBD1 expression in BC mucosal tissue. The research group extracted DNA and amplified the16S rRNA gene from the tissue samples as well. Taxonomic profiling and statistical analysis of mucosal microbiome samples on the CosmosID-HUB Microbiome illustrated increases of Staphylococcus, Corynebacterium and Oxyphotobacteria, and decreases of Faecalibacterium and Bacteroides abundance in tumor samples compared to non-tumor samples. The increase of HBD2 and HBD3 levels in tumor samples were associated with the decrease of Bacteroides, Parabacteroides and Faecalibacterium. In contrast, increased Corynebacterium and Staphylococcus abundance correlated with microbial HBD production. The findings indicate an alteration of the interplay between the microbiome, host and antimicrobial peptides in BC patients, illuminating a potential avenue of research to develop adjuvant antitumor therapies. Click here to read the paper.