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Abstract Objective Bladder cancer(BCa) was a disease that seriously affects patients’ quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer. Methods We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms. Results The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4+T and CD8+T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group. Conclusion P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.

Overactive bladder (OAB) is a condition characterized by an urgency to urinate, which is associated with the urodynamic observation of detrusor overexcitation. Although the etiology of OAB is currently unclear, it has been suggested that in patients with OAB, disruption of bladder epithelial barrier integrity can disturb the normal contractile function of the detrusor. Additionally, dietary preferences have been suggested to influence the severity of OAB. Therefore, the aim of the present study was to investigate the effect of a high salt diet (HSD) on the development of OAB in a murine model. Mice were fed either a HSD or standard diet for 8 weeks, following which voiding characteristics and bladder barrier function were assessed. The present study demonstrated that a HSD in mice was associated with OAB-like symptoms such as increased urinary frequency and non-voiding bladder contractions. The HSD group demonstrated a thinner bladder mucus layer and decreased expression of bladder barrier markers, tight junction protein-1 and claudin-1, which may be potentially indicative of induced bladder damage. A HSD for 8 weeks in mice and a high salt treatment at the uroepithelium cellular (SV-HUC-1s) level resulted in increased uroepithelial oxidative stress and inflammatory cell infiltration, as indicated by increased expression levels of TNF-α and IL-1β, as well as activation of the nucleotide-binding domain leucine-rich-containing family pyrin domain-containing 3 (NLRP3) and NF-κB signaling pathways in vivo and in vitro. Therefore, the present study indicated that a HSD could be a potentially important risk factor for the development of OAB, as it may be associated with overactivation of contractile function of the bladder by impairing the integrity of the bladder epithelial barrier and activation of the NLRP3 and NF-κB signaling pathways. Remodeling of the bladder barrier and reduction of the inflammatory response may be potential targets for the treatment of OAB in the future. [ABSTRACT FROM AUTHOR]