Cyclophosphamide (CTX) is a widely used anticancer drug in clinical practice; however, its administration can lead to gastrointestinal damage and immune suppression. Lactobacillus murinus (L. murinus) has been shown to regulate immune cell activity and protect the gastrointestinal system, showing potential application as a functional food. The objective of this study was to investigate the effects of L. murinus ZNL-13 on CTX-induced intestinal mucosal injury and gut microbiota in mice. The results demonstrated that L. murinus ZNL-13 significantly alleviated weight loss and intestinal pathological damage. Moreover, in CTX-induced intestinal injury mice, L. murinus ZNL-13 enhanced the release of immune factors, suppressed cell apoptosis, and protected the intestinal mucosal barrier. Additionally, it activated the TLR4/NF-κB pathway, thereby promoting immune cell activity. Furthermore, L. murinus ZNL-13 contributed to the restoration of gut microbial homeostasis by increasing the relative abundance of short-chain fatty acid-producing bacteria. Taken together, this investigation highlights the potential of L. murinus ZNL-13 in protecting the intestinal barrier and enhancing immune function while laying the groundwork for its development as a novel probiotic and functional food.

(1) Background: Chronic inflammation is considered an important pathological basis underlying the development and progression of multiple metabolic liver diseases; although hydrogen-rich water (HRW) has shown beneficial effects in acute inflammation, its long-term impact on chronic hepatic inflammation remains unclear. (2) Methods: Sprague–Dawley rats were pretreated with HRW for 8 months, after which a lipopolysaccharide (LPS)-induced rat model of chronic hepatic inflammation was established, with continuous HRW administration throughout the experimental period. (3) Results: Long-term HRW consumption significantly reduced LPS-induced inflammatory cell infiltration in liver tissue, suppressed the abnormal elevation of pro-inflammatory factors, and maintained relatively stable expression levels of anti-inflammatory factors. In addition, HRW attenuated pro-apoptotic signaling associated with the death receptor pathway, mitochondrial pathway, and endoplasmic reticulum stress (including Bax, Cyt c, Caspase-3, Caspase-8, Caspase-9, Caspase-12, CHOP, and GRP78), while preserving the expression of the anti-apoptotic protein Bcl-2, thereby partially preventing the tendency toward hepatocyte apoptosis induced by chronic inflammation. (4) Conclusions: Long-term consumption of HRW may delay the onset and progression of chronic inflammation-related liver injury by alleviating inflammatory responses, oxidative stress, mitochondrial dysfunction, and apoptotic activity, thus exerting a preventive protective effect on the liver.