RT Journal Article SR Electronic T1 Rapid gut dysbiosis induced by stroke exacerbates brain infarction in turn JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 1486 OP 1494 DO 10.1136/gutjnl-2020-323263 VO 70 IS 8 A1 Kaiyu Xu A1 Xuxuan Gao A1 Genghong Xia A1 Muxuan Chen A1 Nianyi Zeng A1 Shan Wang A1 Chao You A1 Xiaolin Tian A1 Huiling Di A1 Wenli Tang A1 Pan Li A1 Huidi Wang A1 Xiuli Zeng A1 Chuhong Tan A1 Fanguo Meng A1 Hailong Li A1 Yan He A1 Hongwei Zhou A1 Jia Yin YR 2021 UL http://gut.bmj.com/content/70/8/1486.abstract AB Objective Stroke 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.Design We 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.Results Brain 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.Conclusions This 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.Data are available in a public, open access repository. Data are available upon reasonable request. The raw data for 16 S rRNA gene sequences for clinical cohorts and animal experiments are available from the European Nucleotide Archive (https://www.ebi.ac.uk/ena/) at accession number PRJEB38503 and PRJEB38504.