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<p>Ulcerative colitis is a chronic inflammatory disease with rising global incidence and limited treatment options. Despite growing interest in probiotic-based therapies, the dose- and time-specific efficacy of antioxidant strains remains poorly defined. Here, we investigated the therapeutic effects of intervention doses (Low, Medium, High) and pre-treatment times (7, 14, 21 days) of <i>Lactiplantibacillus plantarum</i> AS21 on DSS-induced colitis in mice. <i>L. plantarum</i> AS21 significantly reduced disease activity index and histological scores, enhancing IL-10 expression while suppressing IL-1β, IL-6, TNF-α, and IFN-γ (<i>p</i> &lt; 0.05). Colon length shortening was attenuated, and spleen weight was reduced in the treated groups. Oxidative stress markers MDA and MPO decreased, whereas SOD, CAT, and GSH increased in a dose- and time-dependent manner (<i>p</i> &lt; 0.05). Mucosal barrier integrity was restored through claudin-1 and occludin upregulation and increased goblet cell counts (<i>p</i> &lt; 0.05). Alpha diversity showed no significant differences, but beta diversity revealed significant separation across groups (<i>p</i> &lt; 0.05). Beneficial taxa (Firmicutes, <i>Ileibacterium</i>, <i>Allobaculum</i>) were enriched, while pathogenic taxa (<i>Akkermansia</i>, Proteobacteria) were reduced in treated groups (<i>p</i> &lt; 0.05). Anti-inflammatory metabolites (7-dehydrocholesterol, riboflavin, citric acid, lipid derivatives) and short-chain fatty acids were significantly upregulated (<i>p</i> &lt; 0.05). Medium and high doses, together with 14- and 21-day pre-treatment, conferred significantly greater protective effects than 7-day pre-treatment or low-dose groups (<i>p</i> &lt; 0.05). These findings establish precise dose- and time-dependent parameters for maximizing <i>L. plantarum</i> AS21 anti-colitic efficacy, positioning it as a promising candidate for microbiota- and metabolism-targeted UC therapy.</p>

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Lactiplantibacillus plantarum AS21 Reduces Colitis in Mice by Modulating Inflammation, Gut Barrier Function, and Microbiota in an Intervention Dose and Time-dependent Manner

  • 期刊论文

  • 发表日期：

    2026年5月12日

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  • Ali Sher Bacha,
  • Mengyan Chen,
  • Zitong Ding,
  • Mengya Jia,
  • Hu Chen,
  • Ikram Khan,
  • Muhammad Ishaq,
  • Azmat Ullah Jan,
  • Ashiq Khan,
  • Xusheng Guo

摘要

Ulcerative colitis is a chronic inflammatory disease with rising global incidence and limited treatment options. Despite growing interest in probiotic-based therapies, the dose- and time-specific efficacy of antioxidant strains remains poorly defined. Here, we investigated the therapeutic effects of intervention doses (Low, Medium, High) and pre-treatment times (7, 14, 21 days) of Lactiplantibacillus plantarum AS21 on DSS-induced colitis in mice. L. plantarum AS21 significantly reduced disease activity index and histological scores, enhancing IL-10 expression while suppressing IL-1β, IL-6, TNF-α, and IFN-γ (p < 0.05). Colon length shortening was attenuated, and spleen weight was reduced in the treated groups. Oxidative stress markers MDA and MPO decreased, whereas SOD, CAT, and GSH increased in a dose- and time-dependent manner (p < 0.05). Mucosal barrier integrity was restored through claudin-1 and occludin upregulation and increased goblet cell counts (p < 0.05). Alpha diversity showed no significant differences, but beta diversity revealed significant separation across groups (p < 0.05). Beneficial taxa (Firmicutes, Ileibacterium, Allobaculum) were enriched, while pathogenic taxa (Akkermansia, Proteobacteria) were reduced in treated groups (p < 0.05). Anti-inflammatory metabolites (7-dehydrocholesterol, riboflavin, citric acid, lipid derivatives) and short-chain fatty acids were significantly upregulated (p < 0.05). Medium and high doses, together with 14- and 21-day pre-treatment, conferred significantly greater protective effects than 7-day pre-treatment or low-dose groups (p < 0.05). These findings establish precise dose- and time-dependent parameters for maximizing L. plantarum AS21 anti-colitic efficacy, positioning it as a promising candidate for microbiota- and metabolism-targeted UC therapy.