ObjectiveStroke is a leading cause of death and disability worldwide. Neuroprotective approaches have failed in clinical trials, thus warranting therapeutic innovations with alternative targets. The gut microbiota is an important contributor to many risk factors for stroke. However, the bidirectional interactions between stroke and gut microbiota remain largely unknown.DesignWe performed two clinical cohort studies to capture the gut dysbiosis dynamics after stroke and their relationship with stroke prognosis. Then, we used a middle cerebral artery occlusion model to explore gut dysbiosis post-stroke in mice and address the causative relationship between acute ischaemic stroke and gut dysbiosis. Finally, we tested whether aminoguanidine, superoxide dismutase and tungstate can alleviate post-stroke brain infarction by restoring gut dysbiosis.ResultsBrain ischaemia rapidly induced intestinal ischaemia and produced excessive nitrate through free radical reactions, resulting in gut dysbiosis with Enterobacteriaceae expansion. Enterobacteriaceae enrichment exacerbated brain infarction by enhancing systemic inflammation and is an independent risk factor for the primary poor outcome of patients with stroke. Administering aminoguanidine or superoxide dismutase to diminish nitrate generation or administering tungstate to inhibit nitrate respiration all resulted in suppressed Enterobacteriaceae overgrowth, reduced systemic inflammation and alleviated brain infarction. These effects were gut microbiome dependent and indicated the translational value of the brain–gut axis in stroke treatment.ConclusionsThis study reveals a reciprocal relationship between stroke and gut dysbiosis. Ischaemic stroke rapidly triggers gut microbiome dysbiosis with Enterobacteriaceae overgrowth that in turn exacerbates brain infarction.

The link between the gut microbiota and metabolic syndrome (MetS) has attracted widespread attention. Christensenellaceae was recently described as an important player in human health, while its distribution and relationship with MetS in Chinese population is still unknown. This study sought to observe the association between Christensenellaceae and metabolic indexes in a large sample of residents in South China. A total of 4,781 people from the GGMP project were included, and the fecal microbiota composition of these individuals was characterized by 16S rRNA sequencing and analyzed the relation between Christensenellaceae and metabolism using QIIME (Quantitative Insight Into Microbial Ecology, Version 1.9.1). The results demonstrated that microbial richness and diversity were increased in the group with a high abundance of Christensenellaceae, who showed a greater complexity of the co-occurrence network with other bacteria than residents who lacked Christensenellaceae. The enriched bacterial taxa were predominantly represented by Oscillospira, Ruminococcaceae, RF39, Rikenellaceae and Akkermansia as the Christensenellaceae abundance increased, while the abundances of Veillonella, Fusobacterium and Klebsiella were significantly reduced. Furthermore, Christensenellaceae was negatively correlated with the pathological features of MetS, such as obesity, hypertriglyceridemia and body mass index (BMI). We found reduced levels of lipid biosynthesis and energy metabolism pathways in people with a high abundance of Christensenellaceae, which may explain the negative relationship between body weight and Christensenellaceae. In conclusion, we found a negative correlation between Christensenellaceae and MetS in a large Chinese population and reported the geographical distribution of Christensenellaceae in the GGMP study. The association data from this population-level research support the investigation of strains within Christensenellaceae as potentially beneficial gut microbes.

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