Lactiplantibacillus plantarum BF_15 Confers Protection Against Ulcerative Colitis by Orchestrating Gut Microbiota-Barrier-Immune Triad Homeostasis.

Ulcerative colitis (UC) is a prevalent chronic inflammatory bowel disease globally, driven mainly by immune dysregulation and gut microbiota dysbiosis. This study focused on Lactiplantibacillus plantarum BF_15, an infant-derived strain with potential to alleviate UC. Four experimental groups were established, including the control group, DSS group, BF_15 group, and LGG group. Probiotics were administrated at a dosage of 1 × 109 CFU/mL and 0.1 mL/10 g body weight (BW) for 21 days. The therapeutic effects and mechanisms of BF_15 against UC were explored based on physiological indicators, gut microbiota, and tandem mass tag (TMT)-based quantitative proteomics. The results showed that BF_15 intervention significantly reduced the disease activity index (DAI) from 3.00 ± 0.50 to 1.16 ± 0.36 (p < 0.05) and mitigated UC-related symptoms including body weight loss and colon shortening, with colon length restored from 4.43 ± 0.32 cm to 5.41 ± 0.26 cm (p < 0.05). Meanwhile, BF_15 downregulated the levels of pro-inflammatory factors such as interleukin IL-6 and IL-17A, and upregulated the levels of IL-10 (from 565.92 ± 79.40 pg/mL to 656.84 ± 66.01 pg/mL) and secretory immunoglobulin A (SIgA, from 9.75 ± 1.29 μg/mL to 12.79 ± 1.77 μg/mL) (p < 0.05), with a therapeutic effect comparable to that of LGG. Further, gut microbiota analysis demonstrated that BF_15 restored the relative abundance of Bacteroidetes (from 28.02% to 30.85%) and regulated gut microbiota homeostasis. Finally, TMT-based proteomic analysis indicated that BF_15 regulated 528 differentially expressed proteins (DEPs) and exhibited a superior regulatory effect on the antigen presentation and processing (APC) pathway compared with LGG. The above findings provide potential novel therapeutic targets and probiotic strain resources for the treatment of UC.