<p>Slow transit constipation (STC) is a prevalent gastrointestinal disorder caused by colon dysfunction. Poly-γ-glutamic acid (γ-PGA), an anionic polymer known for its moisture retention, degradability, and food safety, was studied for its effects on loperamide-induced STC in mice. Treatment with γ-PGA for one week significantly increased both defecation frequency and fecal water content, with the high-dose group (10&#xa0;g/kg/d) restoring fecal water content to 34.23%, outperforming the low- (16.16%) and medium-dose (27.08%) groups and exceeding the positive control, PEG, by 1.35 times. γ-PGA enhanced intestinal peristalsis and reduced the expression of inflammatory markers (<i>IL-1β</i>, <i>IL-6</i>, <i>caspase-1</i>, <i>TLR2</i>) and water-electrolyte transport genes (<i>AQP3</i>, <i>AQP4</i>, <i>ENaC-β</i>), while improving the expression of tight junction proteins (<i>Claudin-1</i>, <i>Occludin</i>, <i>ZO-1</i>) damaged by loperamide. Histopathological analyses confirmed γ-PGA’s capacity to repair intestinal damage. Additionally, Western Blot analysis indicated reduced AQP3/4 levels in the colon, and molecular docking showed good binding affinity between γ-PGA and AQPs. γ-PGA also positively altered gut microbiota composition. Overall, γ-PGA shows promise in treating STC by modulating aquaporins and gut microbiota.</p>

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Poly-γ-glutamic acid alleviates slow transit constipation by regulating aquaporin and gut microbes

  • Xiaoru Wang,
  • Jie Zhou,
  • Zengkun Sun,
  • Ruilei Jia,
  • Diyi Huang,
  • Dongqi Tang,
  • Tao Xia,
  • Fang Xiao

摘要

Slow transit constipation (STC) is a prevalent gastrointestinal disorder caused by colon dysfunction. Poly-γ-glutamic acid (γ-PGA), an anionic polymer known for its moisture retention, degradability, and food safety, was studied for its effects on loperamide-induced STC in mice. Treatment with γ-PGA for one week significantly increased both defecation frequency and fecal water content, with the high-dose group (10 g/kg/d) restoring fecal water content to 34.23%, outperforming the low- (16.16%) and medium-dose (27.08%) groups and exceeding the positive control, PEG, by 1.35 times. γ-PGA enhanced intestinal peristalsis and reduced the expression of inflammatory markers (IL-1β, IL-6, caspase-1, TLR2) and water-electrolyte transport genes (AQP3, AQP4, ENaC-β), while improving the expression of tight junction proteins (Claudin-1, Occludin, ZO-1) damaged by loperamide. Histopathological analyses confirmed γ-PGA’s capacity to repair intestinal damage. Additionally, Western Blot analysis indicated reduced AQP3/4 levels in the colon, and molecular docking showed good binding affinity between γ-PGA and AQPs. γ-PGA also positively altered gut microbiota composition. Overall, γ-PGA shows promise in treating STC by modulating aquaporins and gut microbiota.