Lactulose Improves Neurological Outcomes by Repressing Harmful Bacteria and Regulating Inflammatory Reactions in Mice After Stroke.

Background and objective Gut microbiota dysbiosis following stroke affects the recovery of neurological function. Administration of prebiotics to counteract post-stroke dysbiosis may be a potential therapeutic strategy to improve neurological function. We aim to observe the effect of lactulose on neurological function outcomes, gut microbiota composition, and plasma metabolites in mice after stroke. Methods Male C57BL/6 mice (20-25 g) were randomly divided into three groups: healthy control, photothrombotic stroke + triple-distilled water, and photothrombotic stroke + lactulose. After 14 consecutive days of lactulose administration, feces, plasma, and organs were collected. 16S rDNA sequencing, plasma untargeted metabolomics, qPCR, flow cytometry and Elisa were performed. Results Lactulose supplementation significantly improved the functional outcome of stroke, downregulated inflammatory reaction, and increased anti-inflammatory factors in both the brain and gut. In addition, lactulose supplementation repaired intestinal barrier injury, improved gut microbiota dysbiosis, and partially amended metabolic disorder after stroke. Conclusion Lactulose promotes functional outcomes after stroke in mice, which may be attributable to repressing harmful bacteria, and metabolic disorder, repairing gut barrier disruption, and reducing inflammatory reactions after stroke.