Abstract
Background and ObjectiveGut 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.MethodsMale 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.ResultsLactulose 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.ConclusionLactulose 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.
Highlights
As technology and science advance, a complex interaction among the brain, gut, and microbiota residing in the gut, which comprises the concept of a microbiota-gut-brain axis, has been gradually accepted (Cryan et al, 2019)
We further calculated infarct volume, and the results showed that lactulose supplementation significantly decreased lesion volumn (Figure 1C)
We found that the brain expression levels of IL1b, tumor necrosis factor a (TNFa), monocyte chemoattractant protein-1 (MCP-1), and TLR4 in the photothrombotic stroke + triple-distilled water (PTS_TDW) group were significantly elevated, even at 14 days after stroke, compared with the healthy control (HC) group; while lactulose supplementation significantly decreased the expression of these factors, as shown in Figures 2A, B
Summary
As technology and science advance, a complex interaction among the brain, gut, and microbiota residing in the gut, which comprises the concept of a microbiota-gut-brain axis, has been gradually accepted (Cryan et al, 2019). Stroke causes gut dysfunction, which involves increased intestinal permeability and dysmotility, leading to gut dysbiosis. Increased intestinal permeability might lead to bacterial translocation, which may result in post-stroke complications, such as pneumonia (Stanley et al, 2016). The results of dysbiosis after stroke differ in various studies. Targeting the microbiota-gutbrain axis provides important new directions to treat or prevent stroke and its complications. 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
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