LPxTG proteins mediate microbial interactions to modulate Lactiplantibacillus plantarum C8 in alleviating antibiotic-associated diarrhea

To address the challenges of intestinal dysbiosis and antibiotic-associated diarrhea (AAD) caused by antibiotic treatment, this study investigated the potential of an LPxTG surface protein overexpression strategy for probiotic modulation. Specifically, we established a co-culture model comprising a recombinant Lactiplantibacillus plantarum C8 strain (overexpressing LPxTG proteins) and the wild-type strain, and evaluated its efficacy in alleviating clindamycin-induced AAD in mice. Our findings indicate that the overexpression of LPxTG proteins enhanced the adhesive colonization capabilities and anti-inflammatory properties of the strain. Crucially, this co-culture model demonstrated significantly superior efficacy in regulating the intestinal microecology compared to single-strain models. Experimental data revealed that the co-culture system not only effectively restored the abundance and diversity of the compromised gut microbiota (P < 0.05) but also exerted protective effects through a dual mechanism: it significantly improved the immune microenvironment by modulating key cytokines (reducing pro-inflammatory interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) while elevating anti-inflammatory interleukin-10 (IL-10)) and repaired the intestinal physical barrier by upregulating the expression of tight junction proteins, Occludin and ZO-1. These results confirm that constructing a co-culture microecological system utilizing LPxTG-overexpressing recombinant strains represents a highly efficient and superior probiotic therapeutic strategy for managing antibiotic-induced intestinal dysbiosis.