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<p>Antibiotics remain the recommended first-line therapy for eradicating <i>Helicobacter pylori</i> infection. However, the harsh gastric physicochemical environment severely limits drug bioavailability, contributing to treatment failure (~10%), gut dysbiosis, and the emergence of antimicrobial resistance. Inspired by <i>H. pylori</i> adhesins binding to gastric epithelial glycan, we developed a biomimetic nanocomposite drug delivery system (BSNG) composed of genetically engineered adhesin-functionalized silk fibroin nanoparticles (BS-NPs) embedded within a fluid silk fibroin hydrogel (FSF-Gel) for targeted anti-<i>H. pylori</i> therapy. BS-NPs exhibit <i>H. pylori</i>-like adhesion to gastric epithelial cells, enabling prolonged gastric retention of over 72&#xa0;h. FSF-Gel provides conformal coverage of the gastric mucus layer and supports sustained antibiotic release, and prevents acid-induced aggregation of the encapsulated BS-NPs. Upon gastric administration, amoxicillin-loaded BSNG (BSNG@Amo) significantly enhanced both peak drug concentrations and extended therapeutic retention in gastric tissue. In vivo antibacterial studies confirmed that BSNG@Amo achieved superior <i>H. pylori</i> eradication compared to conventional amoxicillin at equivalent doses. Notably, reduced-frequency BSNG@Amo administration maintained therapeutic efficacy while markedly preserving gut microbiota homeostasis. These results highlight BSNG as a precise, long-acting, and microbiota-sparing platform for sustainable gastric antibiotic delivery.</p> Graphical abstract <p></p>

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Silk-based biomimetic nanocomposite for precision eradication of Helicobacter pylori and gut microbiome preservation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月27日

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  • Guangcheng Huang,
  • Chi Tian,
  • Qingsong Liu,
  • Yuancheng Wang,
  • Feng Wang,
  • Qingxiu He,
  • Qingyou Xia,
  • Ping Zhao

摘要

Antibiotics remain the recommended first-line therapy for eradicating Helicobacter pylori infection. However, the harsh gastric physicochemical environment severely limits drug bioavailability, contributing to treatment failure (~10%), gut dysbiosis, and the emergence of antimicrobial resistance. Inspired by H. pylori adhesins binding to gastric epithelial glycan, we developed a biomimetic nanocomposite drug delivery system (BSNG) composed of genetically engineered adhesin-functionalized silk fibroin nanoparticles (BS-NPs) embedded within a fluid silk fibroin hydrogel (FSF-Gel) for targeted anti-H. pylori therapy. BS-NPs exhibit H. pylori-like adhesion to gastric epithelial cells, enabling prolonged gastric retention of over 72 h. FSF-Gel provides conformal coverage of the gastric mucus layer and supports sustained antibiotic release, and prevents acid-induced aggregation of the encapsulated BS-NPs. Upon gastric administration, amoxicillin-loaded BSNG (BSNG@Amo) significantly enhanced both peak drug concentrations and extended therapeutic retention in gastric tissue. In vivo antibacterial studies confirmed that BSNG@Amo achieved superior H. pylori eradication compared to conventional amoxicillin at equivalent doses. Notably, reduced-frequency BSNG@Amo administration maintained therapeutic efficacy while markedly preserving gut microbiota homeostasis. These results highlight BSNG as a precise, long-acting, and microbiota-sparing platform for sustainable gastric antibiotic delivery.

Graphical abstract