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

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.