Pediococcus acidiactii alleviates Shigella induced colitis

Background: Shigellosis is a major worldwide health problem that mainly affects young children everywhere, and Shigella flexneri is one of the most common pathogens causing this disease. Epidemiological studies show that pathogenic bacteria associated with intestinal disorder can be transferred to humans, like pet owners and clinical staffs, therefore leading to development of intestinal disease. This study aimed to investigate whether supplementing with Pediococcus acidilactici has a beneficial effect on colitis induced by Shigella flexneri, as well as to uncover the possible mechanisms involved.Results: Through fecal microbiota transplantation (FMT), pediococcus acidilactici in the intestines of healthy dogs may be the main cause affecting fecal morphology and nutrient absorption. To verify this hypothesis, the isolated Pediococcus acidilactici was used to feed the Shigella-infected mouse. The experimental results show that Pediococcus acidilactici can significantly improve the intestinal barrier function of mice, reduce inflammatory responses, and alleviate oxidative stress. In addition, when we administered Pediococcus acidilactici orally to the dogs with diarrhea, we found that the morphology of their feces changed significantly before and after feeding, and the digestibility of nutrients also improved significantly. Furthermore, untargeted metabolomic profiling was employed to analyze the in vivo and in vitro fermentation metabolites of Pediococcus acidilactici, the key role of nicotinic acid ribonucleoside (NAR) in this mechanism was identified through investigations. To deeply explore the mechanism of action of NAR, NAR solution at a concentration of 10 mg/mL was injected to mice with Shigella-induced enteritis. Experimental evidence demonstrates that NAR significantly elevates intestinal nicotinamide adenine dinucleotide (NAD+) levels in mice, subsequently activating the SIRT1-FOXO3 signaling axis. This cascade promotes macrophage polarization toward the anti-inflammatory M2 phenotype, thereby effectively mitigating Shigella-induced colonic cell pyroptosis and inflammatory responses.Conclusion: Our research indicates that Shigella may be a potential pathogen causing diarrhea due to intestinal barrier disruption in dogs. Pediococcus acidilactici, as a potential probiotic, can effectively alleviate colitis caused by Shigella through the NAR-SIRT1-FOXO3 signaling pathway.