This study is reported by Lizeng Gao's group from the Institute of Biophysics, Chinese Academy of Sciences, Beijing. The growing issue of antibiotic resistance necessitates alternative treatments for the highly prevalent Helicobacter pylori infection. Gao's group has unexpectedly identified hydrogen polysulfide (H₂Sₙ, n≥2) as an active anti-H. pylori compound in garlic, rather than organic polysulfides. Mechanistic studies reveal that H₂Sₙ specifically inactivates H. pylori glucose-6-phosphate dehydrogenase (G6PDH) by disrupting the electron transfer process between glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide phosphate (NADP⁺). However, garlic derivatives produce low yields of H₂Sₙ, limiting their effectiveness as reliable H₂Sₙ donors for treating H. pylori infection.
To overcome this challenge, Gao's group developed a polysulfide transformation process that converts garlic-derived organosulfur compounds into Fe₃S₄, achieving a 25- to 58-fold increase in H₂Sₙ yield. Furthermore, the development of a chitosan-encapsulated gastric-adaptive H₂Sₙ microreactor (GAPSR) significantly enhanced the treatment outcomes. Under gastric conditions, GAPSR demonstrated 250 times higher efficacy in eradicating H. pylori compared to conventional methods. Remarkably, a single GAPSR treatment achieved a faster eradication of H. pylori than combined antibiotic therapy, while preserving gut microbiota integrity.
These findings highlight a novel mechanism of action driven by polysulfides, presenting a promising alternative strategy for combating H. pylori infections.
