Lactobacillus plantarum Lp2 alleviates the splenic and intestinal injury in cyclophosphamide-induced mice

As a frontline chemotherapeutic agent, cyclophosphamide (CTX) frequently induces severe treatment-related adverse effects. Probiotics have emerged as promising dietary adjuvants to alleviate chemotherapy-induced toxicity. This study aimed to explore the alleviate mechanism of Lactobacillus plantarum Lp2 isolated from a traditional fermented food on CTX-induced splenic and intestinal injuries. In CTX-induced mice, oral Lp2 concurrently activated the TLR2/NF-κB/NLRP3 and Nrf2/HO-1 signaling pathways in the spleen, thereby enhancing the levels of cytokines (IL-2, IL-6, IL-1β, TNF-α, and IFN-γ) and the activity of antioxidant enzymes (CAT, SOD, and GSH), protecting splenic architecture and function. Intestinal NLRP3 inflammasome activation by Lp2 modulated similar cytokine profiles (IL-2, IL-6, IL-1β, TNF-α, IFN-γ), demonstrating its gut- immunoregulatory capacity in CTX-induced mice. Furthermore, Lp2 enhanced short-chain fatty acid (SCFA) metabolism and intestinal barrier by modulating the gut microbiota composition through specific bacterial populations, including Clostridium, Duncaniella, Alistipes, Muribaculum, among others, thereby sustaining intestinal physiological homeostasis. These findings established Lp2 as a multifunctional probiotic capable of mitigating CTX chemotherapy-associated side effects, providing a theoretical basis for the development of probiotic dietary supplements.