Autophagy-driven modulation of stem cell dynamics in -induced gastric diseases in mice.

Chronic infection is a major contributor to gastric disease progression, with its involvement in autophagy and stem cell dynamics playing a critical role in disease mechanisms. This study investigated how . , particularly in combination with the carcinogen N-nitroso-N-methylurea (NMU), disrupted autophagy and stem cell function, driving gastric pathology. . infection significantly increased autophagy, promoted the epithelial-mesenchymal transition, suppressed and expression in mouse gastric organoids, and enhanced stem cell proliferation (organoid numbers increased 92% compared to control at 24 weeks,  < 0.001), while NMU caused milder autophagy, severe inflammation, glandular dilation, and reduced stemness markers (CD133 decreased 30% at 24 weeks,  < 0.05). Combined . and NMU exposure synergistically dysregulated / expression, exacerbated autophagic flux disruption, and impaired stem cell function, reducing organoid budding (decreased 43% vs. . alone at 36 weeks,  < 0.01) and dysregulating , , , and expression. Pathologically, this combination led to severe gastric damage, including intestinal metaplasia and neutrophil infiltration. Chloroquine (CQ) treatment mitigates these effects by reversing autophagic dysfunction, restoring stem cell capacity ( increased 97% at 44 weeks,  < 0.05), differentially modulating /: potentiating and suppressing Ghrelin, normalizing organoid growth, attenuating the EMT, and reducing inflammation, particularly in the .  + NMU group. These findings elucidate how . and NMU drive gastric pathology through autophagy-stem cell crosstalk and highlight CQ's potential as a targeted therapeutic strategy for infection-associated gastric damage.