Abstract: Objective: To investigate the effects of seaweed polysaccharides fermented by Pediococcus pentosaceus CQFP202447 on alleviating antibiotic-induced neuroinflammation and oxidative stress and the regulatory effect on the intestinal flora in mice. Methods: A mixed antibiotic preparation was used to create a mouse model by intraperitoneal injection. After the experiment, weight-bearing swimming and exhaustive running time, liver index, oxidative and inflammatory indexes of the serum and brain, and intestinal flora composition were measured. The pathological changes of brain tissue were observed by hematoxylin-eosin (HE) staining. The expression of inflammatory pathway genes in the brain and the expression of key intestinal barrier genes were detected by using real-time quantitative polymerase chain reaction (qPCR). Results: Compared with the model group, P. pentosaceus CQFP202447 and its fermented preparation (PP-PS) significantly prolonged the weight-bearing swimming and running time of mice (P < 0.05), the latter being more effective, while liver index did not change significantly (P > 0.05). HE staining showed that both of them improved the cell morphology of mouse brain tissue, increased the number of cells, and reduced pyknosis. Meanwhile, they reduced the levels of malondialdehyde (MDA), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum and brain, and increased the levels of superoxide dismutase (SOD), glutathione (GSH) and IL-10. PP-PS showed more significant effect in down-regulating MDA and TNF-α levels in the serum and in up-regulating SOD and IL-10 levels in brain tissue (P < 0.05). Both CQFP202447 and PP-PS activated and enhanced the gene expression of Akt, Creb, Bdnf, Erk1 in the brain, the latter being more effective in this regard. In addition, they regulated the intestinal flora, changing the α and β diversity, increasing the relative abundance of the beneficial bacteria Muribaculaceae, Akkermansia, Prevotella and Lachnospiraceae, and reducing the relative abundance of the harmful bacterium Desulfovibrio. Conclusion: P. pentosaceus CQFP202447 and its fermented preparation can reduce antibiotic-induced neuroinflammation and oxidative stress and simultaneously improve the composition of intestinal flora. This study provides a theoretical basis for understanding the role of P. pentosaceus CQFP202447 and its fermented preparation in alleviating neuroinflammation and oxidative stress and promoting intestinal health, thereby providing new ideas for the development of related functional foods.

Key words: Pediococcus pentosaceus CQFP202447; seaweed polysaccharides; antibiotics; motor function; brain; intestinal flora