Pancreatic ductal adenocarcinoma has an extremely poor prognosis. Pancreatic ductal adenocarcinoma harbors a multidomain intratumoral microbial community dominated by bacteria and also containing fungi; its composition differs fundamentally from that of normal pancreatic tissue and drives malignant progression through three major axes: inflammatory-immune signaling, metabolic-epigenetic regulation, and stromal remodeling. Gammaproteobacterial lipopolysaccharide establishes a chronic proinflammatory microenvironment through the Toll-like receptor 4-nuclear factor kappa B axis, whereas in situ gemcitabine inactivation by the long isoform of bacterial cytidine deaminase represents the best-supported microbiome-mediated mechanism of drug resistance to date. In experimental systems, Fusobacterium nucleatum has been linked to tumor-cell invasion and alternatively activated macrophage polarization. In mouse and cell models, intratumoral fungi have been implicated in immunosuppressive signaling through the C-type lectin receptor dectin-1-interleukin 33 axis and the mannose-binding lectin-complement pathway; their relevance to human pancreatic ductal adenocarcinoma remains debated. These three axes may converge on stromal activation and epithelial-mesenchymal transition and contribute to invasion and treatment resistance. Antimicrobial strategies targeting drug-resistance-associated bacteria can restore gemcitabine efficacy in animal experiments and have been explored experimentally alongside programmed cell death protein 1 blockade; the clinically appropriate patient populations and optimal sequencing of such combinations remain to be defined in prospective trials.

Irritable bowel syndrome is a disorder of gut–brain interaction characterized by recurrent abdominal pain and altered bowel habits. Interactions among intestinal microorganisms and their metabolites, the epithelial barrier, mucosal immunity, and gut–brain signaling provide important insights into the heterogeneity of this condition. Engineered micro- and nanoscale carriers may improve the stability of orally administered bioactive agents and facilitate local intestinal delivery while modulating relevant pathological processes through protection of viable microorganisms, delivery of microbial metabolites, or direct regulation of host cells. This review examines major mechanisms underlying microbiota–immune interactions and summarizes advances in colon-targeted delivery, protective carriers for probiotics, plant-derived vesicle-like preparations, and microalgae-based hybrid systems. We further discuss the biological characteristics of different clinical subtypes and key translational challenges, including safety, quality control, and rigorous verification of therapeutic efficacy. In particular, evidence from direct irritable bowel syndrome studies is distinguished from findings in symptom-based models, other disease models, and fundamental mechanistic experiments.