Abstract
Crohn’s disease (CD) is a chronic gastrointestinal disorder involving host genetics, environment, and gut microbiota, with microbial-based approaches holding high therapeutic potential. This study focused on the potential of Lactobacillus plantarum to attenuate intestinal inflammation in SAMP1/YitFc mouse models of colitis and ileitis. We tested the potential of L. plantarum to; (i) protect against the severity of dextran sodium sulfate (DSS)-induced colitis (acute flare model), (ii) prolong Dexamethasone (DEX)-induced remission in older SAMP mice with established ileitis (remission model), (iii) prevent/attenuate disease onset in young SAMP mice (preclinical model). Body weight, fecal myeloperoxidase (fMPO), gut permeability (fluorescein isothiocyanate (FITC)-dextran), colonoscopy, 3-D stereomicroscopy and histology of intestinal tissues were assessed. Administration of L. plantarum (Lac) significantly attenuated intestinal inflammation across multiple SAMP mouse models. In DSS-induced colitis, treatment improved clinical and histologic disease activity, evidenced by greater weight retention, preserved colon length, enhanced barrier integrity, and reduced fMPO and colonoscopy scores (Lac: 3.1 ± 0.8 vs. control: 5.3 ± 1.2, p = 0.02). In DEX-induced remission model, L. plantarum prolonged remission and reduced relapse severity, demonstrated by improved weight maintenance, decreased gut permeability and inflammatory burden, and lower histologic scores (Lac: 6.0 ± 2.1 vs. control; 9.6 ± 2.0, p = 0.03). Early-life intervention further mitigated spontaneous ileitis, with reductions in intestinal permeability, inflammatory activity, and macroscopic lesion severity (Lac: 0.6 ± 0.7 vs. control: 1.9 ± 0.6, p = 0.03). L. plantarum improved gut barrier integrity and attenuated intestinal inflammation in experimental colitis and chronic ileitis models of IBD.