The microbiota refers to the assemblage of microorganisms present in a particular environment, which can maintain homeostasis and modulate immune function in the human body. Microbiota dysbiosis disrupts bodily functions, leading to a series of human diseases, including cancer. Recent studies have suggested that tumor microbiota play important roles in the tumorigenesis of bladder cancer (BLCA), including malignant proliferation, invasion and metastasis, chemo-radiotherapy resistance, and immune response. In this review, we systemically classify the microbiota of the digestive and urinary systems associated with BLCA, as well as the intratumoral microbiota within BLCA tissue. This review provides a comprehensive summary of the characteristics of these microbial populations and explores their potential roles in the development, detection, diagnosis, and treatment of BLCA, with a focus on immunotherapy, while also discussing existing problems and possible development directions. Given the complexity and breadth of this field, clinicians should carefully consider the influence of the microbiota throughout the entire diagnostic and therapeutic process for BLCA.
Neutrophil dysfunction and activation of the absent in melanoma 2 (AIM2) inflammasome have been implicated in ulcerative colitis (UC) pathogenesis. However, whether these two immune responses interact synergistically and their precise role in UC remains unclear. Here, we performed bioinformatics and clinical analyses to assess neutrophil extracellular traps (NETs) and AIM2 inflammasome cascades in UC, including their correlation. Dual immunofluorescence revealed the predominant cell types expressing AIM2. Neutrophil activation and NETs release were examined in Fusobacterium nucleatum ( Fn )-stimulated cell models, while in vitro and in vivo studies investigated the effect of NETs on AIM2 inflammasome activation, UC severity, and therapeutic potential. Bioinformatics revealed co-up-regulation and significant co-expression of AIM2 inflammasome cascade-related genes and NETs-related genes in active UC. Confocal imaging showed that AIM2 primarily localized to intestinal epithelial cells in intestinal biopsies from UC patients and colon tissues from UC model mice. Fn infection partially promoted neutrophil activation and the release of NETs via neutrophil extracellular vesicles (nEVs). NETs were carried by nEVs and internalized by intestinal epithelial cells, subsequently triggering AIM2 inflammasome-dependent pyroptosis. In vivo studies demonstrated that elevated AIM2 inflammasome-related indicators triggered by Fn -stimulated nEVs-NETs were related to UC severity. Therapeutically, blockade of the nEVs-NETs/AIM2 inflammasome cascade using the NET-degrading agent DNase I or the AIM2 inhibitor A151 effectively attenuated colitis. Collectively, AIM2 inflammasome cascade activation by NETs-laden nEVs triggered by Fn exacerbates ulcerative colitis, highlighting the nEVs-NETs/AIM2 inflammasome cascade as a promising therapeutic target.
Moyamoya disease (MMD) is a progressive cerebrovascular disorder characterized by arterial stenosis and compensatory neovascularization, but its upstream drivers remain poorly defined. Here, we identify Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), a traditionally probiotic species, as a context-dependent pathobiont. Integrated metagenomic and metabolomic analyses revealed enrichment of B. pseudocatenulatum in MMD, closely associated with elevated microbial-derived histamine and serotonin. In mice, chronic oral administration of B. pseudocatenulatum disrupted intestinal barrier integrity and increased gut microbial production and systemic levels of histamine and serotonin. These changes were accompanied by systemic inflammation and activation of angiogenic pathways, which together promoted MMD-relevant cerebrovascular remodeling in experimental models. Notably, direct administration of histamine or serotonin to mice reproduced key MMD-like vascular phenotypes, supporting the conclusion that these microbial metabolites are sufficient to induce selected MMD-relevant vascular changes in experimental models. Our findings propose a microbial–metabolite–vascular axis and suggest that the role of specific Bifidobacterium strains may be more nuanced than previously recognized. These results provide a mechanistic framework for understanding the gut–brain axis in neurovascular pathology and nominate the microbiome and its metabolic products as potential targets for non-invasive diagnostics and precision therapeutic interventions in MMD.
