When metabolic disease rewrites infection biology: Long-term multiorgan consequences of Helicobacter pylori infection in diabetes

Figure 1 Proposed mechanistic pathway from Helicobacter pylori infection under diabetic conditions to multiorgan injury. The stepwise pathway depicts: (1) Impaired mucosal immunity allowing prolonged gastric colonization; (2) Irreversible mucosal fibrosis and inflammation; (3) Exosome/outer membrane vesicles-mediated extra-gastric antigen translocation via the portal circulation; (4) Hepatic NF-κB activation and non-alcoholic fatty liver disease progression; (5) Renal cytokine-mediated podocyte injury; (6) Compounded microbiota dysbiosis with metabolic endotoxemia; and (7) Convergent systemic apoptotic signalling. NAFLD: Non-alcoholic fatty liver disease; OMV: Outer membrane vesicles; NASH: Non-alcoholic steatohepatitis; IL: Interleukin; TNF-α: Tumor necrosis factor-alpha; SCFA: Short-chain fatty acid; LPS: Lipopolysaccharide; H. pylori: Helicobacter pylori.

Figure 2 Schematic overview of the host-pathogen-metabolic axis in diabetic Helicobacter pylori infection. Hyperglycaemia-driven immune suppression prolongs H Helicobacter pylori gastric colonization, triggering progressive mucosal inflammation, exosome-mediated virulence factor dissemination to the liver, compounded gut microbiota dysbiosis, and convergent apoptosis across the pancreas, liver, and kidneys. Divergent arrows illustrate the temporal dissociation between bacterial load decline and persistent tissue injury. NAFLD: Non-alcoholic fatty liver disease; OMV: Outer membrane vesicles; IL: Interleukin; TNF-α: Tumor necrosis factor-alpha; LPS: Lipopolysaccharide; H. pylori: Helicobacter pylori.

Figure 3 Proposed clinical algorithm for Helicobacter pylori management in patients with type 2 diabetes mellitus. A stepwise algorithm is proposed integrating: (1) Universal Helicobacter pylori screening at type 2 diabetes mellitus diagnosis; (2) Virulence genotyping (CagA/VacA) for risk stratification; (3) Early eradication with glycemic co-optimization; (4) Probiotic adjunction for microbiota resilience; and (5) Post-eradication multiorgan surveillance encompassing hepatic function, renal parameters, and HbA1c. H. pylori: Helicobacter pylori; T2DM: Type 2 diabetes mellitus; ALT: Alanine aminotransferase; UBT: Urea breath test; LFT: Liver function test; uACR: Urine albumin-to-creatinine ratio; eGFR: Estimated glomerular filtration rate.