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<p>Chronic, relapsing colonic inflammation defines ulcerative colitis (UC) and heightens long-term colorectal cancer risk. Probiotics, proven beneficial, have emerged as a promising adjunctive strategy for UC management. We conducted a two-tiered evaluation of the breast-milk-derived strain <i>Lactobacillus gasseri</i> FN136. In vitro, FN136 secreted anti-inflammatory amino acids and indole derivatives‌, displayed pronounced acid- and bile-salt tolerance, and exhibited significant antimicrobial activity. In vivo, daily oral administration of 1 × 10⁹ CFU FN136 markedly attenuated DSS-induced UC: serum L-arginine was restored, splenic regulatory T cells frequency increased by 42.09% (<i>P</i> &lt; 0.05), and nitric oxide production was elevated, while disease activity index, body-weight loss, and colonic shortening were all significantly reduced (<i>P</i> &lt; 0.05). Histopathology revealed intact crypt architecture and diminished inflammatory infiltration; systemic inflammation was suppressed as evidenced by decreased interleukin-6, myeloperoxidase, lipopolysaccharide, and FITC-dextran levels (<i>P</i> &lt; 0.05). However, 16&#xa0;S rRNA sequencing revealed no significant alterations in global microbial composition, indicating that FN136 exerts protection <i>via</i> a microbiota-independent postbiotic–host axis. Collectively, FN136 mitigates DSS-induced UC by restoring serum arginine and orchestrating immune–barrier homeostasis through a postbiotic pathway, offering a novel framework for precision UC intervention.</p>

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Breast-Milk Lactobacillus Gasseri FN136 Alleviates DSS-Induced Ulcerative Colitis Through Microbiota-Independent Metabolite–Host Interactions

  • 期刊论文

  • 发表日期：

    2025年11月28日

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  • Qingcui Li,
  • Wenhao Wang,
  • Fan Zhou,
  • Xin Geng,
  • Ce Qi,
  • Chengwen Li,
  • Jin Sun

摘要

Chronic, relapsing colonic inflammation defines ulcerative colitis (UC) and heightens long-term colorectal cancer risk. Probiotics, proven beneficial, have emerged as a promising adjunctive strategy for UC management. We conducted a two-tiered evaluation of the breast-milk-derived strain Lactobacillus gasseri FN136. In vitro, FN136 secreted anti-inflammatory amino acids and indole derivatives‌, displayed pronounced acid- and bile-salt tolerance, and exhibited significant antimicrobial activity. In vivo, daily oral administration of 1 × 10⁹ CFU FN136 markedly attenuated DSS-induced UC: serum L-arginine was restored, splenic regulatory T cells frequency increased by 42.09% (P < 0.05), and nitric oxide production was elevated, while disease activity index, body-weight loss, and colonic shortening were all significantly reduced (P < 0.05). Histopathology revealed intact crypt architecture and diminished inflammatory infiltration; systemic inflammation was suppressed as evidenced by decreased interleukin-6, myeloperoxidase, lipopolysaccharide, and FITC-dextran levels (P < 0.05). However, 16 S rRNA sequencing revealed no significant alterations in global microbial composition, indicating that FN136 exerts protection via a microbiota-independent postbiotic–host axis. Collectively, FN136 mitigates DSS-induced UC by restoring serum arginine and orchestrating immune–barrier homeostasis through a postbiotic pathway, offering a novel framework for precision UC intervention.