This Research Topic invites mechanistic studies that elucidate how commensal and probiotic microorganisms—or their purified/secreted factors—attenuate pathogen virulence within the gut. We seek work that dissects causal cellular pathways by which beneficial microbes restrict colonization, suppress virulence gene expression, modulate quorum sensing, block adhesion/invasion, and disrupt biofilm formation at intestinal epithelial interfaces. We particularly welcome investigations leveraging gnotobiotic systems, intestinal organoids, gut-on-chip platforms, and infection-relevant co-cultures to resolve host–microbe–pathogen interactions with single-cell and spatial readouts. Studies examining metabolite-mediated crosstalk (e.g., SCFAs, bile acid derivatives, bacteriocins), contact-dependent inhibition, receptor competition, and barrier fortification are encouraged, as are rigorous characterizations of pathogen-facing outcomes (transcriptional programs, virulence effectors, adhesion kinetics, biofilm architecture).

Translational contributions that bridge mechanism to therapy are a priority, including rational design of probiotic consortia, engineered strains, targeted delivery systems (e.g., encapsulation, mucoadhesive carriers), and combination strategies with antibiotics or antimicrobial peptides. We welcome work quantifying impacts on antimicrobial tolerance and resistance trajectories, and defining pharmacodynamic principles for anti-virulence interventions in the gut. Multimodal approaches—spanning genetics, chemical biology, metabolomics, imaging, and computational modeling—are highly suitable, provided they offer mechanistic resolution and reproducible, infection-relevant endpoints. Reviews and perspectives are invited if they synthesize emerging mechanistic frameworks, standardize readouts, or chart translational pathways from bench to clinic.

We welcome articles addressing, but not limited to, the following themes:

-Mechanistic suppression of pathogen virulence programs by commensals/probiotics (gene regulation, quorum sensing, effector delivery)
-Competitive exclusion and receptor competition at the intestinal epithelium; mucus and glycocalyx-mediated interactions
-Secreted and surface-associated probiotic factors (bacteriocins, SCFAs, indoles, bile acid metabolites, T6SS/T7SS interactions) with defined targets
-Host epithelial and innate immune pathways mediating anti-virulence effects (barrier integrity, AMP induction, inflammasome/TLR signaling)
-Biofilm inhibition/disruption in gut-relevant pathogens with structural and functional readouts
-Gnotobiotic, organoid, and gut-on-chip models enabling causal, cellular-resolution analyses
-Combination strategies with antibiotics/AMPs; impacts on tolerance, persistence, and resistance evolution
-Encapsulation and targeted delivery systems that enhance site-specific anti-virulence efficacy
-Standardized assays and quantitative metrics for pathogen-side outcomes (adhesion/invasion, biomass, transcriptomics, virulence phenotypes)
-Computational and systems approaches linking microbial metabolites, host signaling, and pathogen responses to guide therapeutic design

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Probiotic and Commensal Modulation of Pathogen Virulence: Cellular Pathways and Therapeutic Implications