Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke

Background: Significant dysbiosis occurs in the gut microbiome of stroke patients. Condensing these broad, complex changes into one index would greatly facilitate the clinical usage of gut microbiome data. Here, we formulated a gut microbiota index in patients with acute ischemic stroke based on the...

Full description

Bibliographic Details
Main Authors: Geng-Hong Xia, Chao You, Xu-Xuan Gao, Xiu-Li Zeng, Jia-Jia Zhu, Kai-Yu Xu, Chu-Hong Tan, Ruo-Ting Xu, Qi-Heng Wu, Hong-Wei Zhou, Yan He, Jia Yin
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-04-01
Series:Frontiers in Neurology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fneur.2019.00397/full
_version_ 1828748979791200256
author Geng-Hong Xia
Chao You
Chao You
Xu-Xuan Gao
Xiu-Li Zeng
Jia-Jia Zhu
Kai-Yu Xu
Chu-Hong Tan
Ruo-Ting Xu
Qi-Heng Wu
Hong-Wei Zhou
Yan He
Jia Yin
author_facet Geng-Hong Xia
Chao You
Chao You
Xu-Xuan Gao
Xiu-Li Zeng
Jia-Jia Zhu
Kai-Yu Xu
Chu-Hong Tan
Ruo-Ting Xu
Qi-Heng Wu
Hong-Wei Zhou
Yan He
Jia Yin
author_sort Geng-Hong Xia
collection DOAJ
description Background: Significant dysbiosis occurs in the gut microbiome of stroke patients. Condensing these broad, complex changes into one index would greatly facilitate the clinical usage of gut microbiome data. Here, we formulated a gut microbiota index in patients with acute ischemic stroke based on their gut microbiota dysbiosis patterns and tested whether the index was correlated with brain injury and early outcome.Methods: A total of 104 patients with acute ischemic stroke and 90 healthy individuals were recruited, and their gut microbiotas were compared and to model a Stroke Dysbiosis Index (SDI), which representing stroke-associated dysbiosis patterns overall. Another 83 patients and 70 controls were recruited for validation. The association of SDI with stroke severity (National Institutes of Health Stroke Scale [NIHSS] score) and outcome (modified Rankin scale [mRS] score: favorable, 0–2; unfavorable, >2) at discharge was also assessed. A middle cerebral artery occlusion (MCAO) model was used in human flora-associated (HFA) animals to explore the causal relationship between gut dysbiosis and stroke outcome.Results: Eighteen genera were significantly different between stroke patients and healthy individuals. The SDI formula was devised based on these microbiome differences; SDI was significantly higher in stroke patients than in healthy controls. SDI alone discriminated stroke patients from controls with AUCs of 74.9% in the training cohort and 84.3% in the validation cohort. SDI was significantly and positively correlated with NIHSS score on admission and mRS score at discharge. Logistic regression analysis showed that SDI was an independent predictor of severe stroke (NIHSS ≥8) and early unfavorable outcome (mRS >2). Mice receiving fecal transplants from high-SDI patients developed severe brain injury with elevated IL-17+ γδ T cells in gut compared to mice receiving transplants from low-SDI patients (all P < 0.05).Conclusions: We developed an index to measure gut microbiota dysbiosis in stroke patients; this index was significantly correlated with patients' outcome and was causally related to outcome in a mouse model of stroke. Our model facilitates the potential clinical application of gut microbiota data in stroke and adds quantitative evidence linking the gut microbiota to stroke.
first_indexed 2024-12-10T11:44:48Z
format Article
id doaj.art-c16302f3d3934f41a8b6f5c188fd36c8
institution Directory Open Access Journal
issn 1664-2295
language English
last_indexed 2024-12-10T11:44:48Z
publishDate 2019-04-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Neurology
spelling doaj.art-c16302f3d3934f41a8b6f5c188fd36c82022-12-22T01:50:07ZengFrontiers Media S.A.Frontiers in Neurology1664-22952019-04-011010.3389/fneur.2019.00397444987Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of StrokeGeng-Hong Xia0Chao You1Chao You2Xu-Xuan Gao3Xiu-Li Zeng4Jia-Jia Zhu5Kai-Yu Xu6Chu-Hong Tan7Ruo-Ting Xu8Qi-Heng Wu9Hong-Wei Zhou10Yan He11Jia Yin12Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, The First People's Hospital of Zunyi, Zunyi, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaState Key Laboratory of Organ Failure Research, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaState Key Laboratory of Organ Failure Research, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaMicrobiome Medicine Center, Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, ChinaDepartment of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, ChinaBackground: Significant dysbiosis occurs in the gut microbiome of stroke patients. Condensing these broad, complex changes into one index would greatly facilitate the clinical usage of gut microbiome data. Here, we formulated a gut microbiota index in patients with acute ischemic stroke based on their gut microbiota dysbiosis patterns and tested whether the index was correlated with brain injury and early outcome.Methods: A total of 104 patients with acute ischemic stroke and 90 healthy individuals were recruited, and their gut microbiotas were compared and to model a Stroke Dysbiosis Index (SDI), which representing stroke-associated dysbiosis patterns overall. Another 83 patients and 70 controls were recruited for validation. The association of SDI with stroke severity (National Institutes of Health Stroke Scale [NIHSS] score) and outcome (modified Rankin scale [mRS] score: favorable, 0–2; unfavorable, >2) at discharge was also assessed. A middle cerebral artery occlusion (MCAO) model was used in human flora-associated (HFA) animals to explore the causal relationship between gut dysbiosis and stroke outcome.Results: Eighteen genera were significantly different between stroke patients and healthy individuals. The SDI formula was devised based on these microbiome differences; SDI was significantly higher in stroke patients than in healthy controls. SDI alone discriminated stroke patients from controls with AUCs of 74.9% in the training cohort and 84.3% in the validation cohort. SDI was significantly and positively correlated with NIHSS score on admission and mRS score at discharge. Logistic regression analysis showed that SDI was an independent predictor of severe stroke (NIHSS ≥8) and early unfavorable outcome (mRS >2). Mice receiving fecal transplants from high-SDI patients developed severe brain injury with elevated IL-17+ γδ T cells in gut compared to mice receiving transplants from low-SDI patients (all P < 0.05).Conclusions: We developed an index to measure gut microbiota dysbiosis in stroke patients; this index was significantly correlated with patients' outcome and was causally related to outcome in a mouse model of stroke. Our model facilitates the potential clinical application of gut microbiota data in stroke and adds quantitative evidence linking the gut microbiota to stroke.https://www.frontiersin.org/article/10.3389/fneur.2019.00397/fullstrokebrain injurymicrobiota dysbiosisfecal microbiome transplantationoutcome
spellingShingle Geng-Hong Xia
Chao You
Chao You
Xu-Xuan Gao
Xiu-Li Zeng
Jia-Jia Zhu
Kai-Yu Xu
Chu-Hong Tan
Ruo-Ting Xu
Qi-Heng Wu
Hong-Wei Zhou
Yan He
Jia Yin
Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke
Frontiers in Neurology
stroke
brain injury
microbiota dysbiosis
fecal microbiome transplantation
outcome
title Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke
title_full Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke
title_fullStr Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke
title_full_unstemmed Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke
title_short Stroke Dysbiosis Index (SDI) in Gut Microbiome Are Associated With Brain Injury and Prognosis of Stroke
title_sort stroke dysbiosis index sdi in gut microbiome are associated with brain injury and prognosis of stroke
topic stroke
brain injury
microbiota dysbiosis
fecal microbiome transplantation
outcome
url https://www.frontiersin.org/article/10.3389/fneur.2019.00397/full
work_keys_str_mv AT genghongxia strokedysbiosisindexsdiingutmicrobiomeareassociatedwithbraininjuryandprognosisofstroke
AT chaoyou strokedysbiosisindexsdiingutmicrobiomeareassociatedwithbraininjuryandprognosisofstroke
AT chaoyou strokedysbiosisindexsdiingutmicrobiomeareassociatedwithbraininjuryandprognosisofstroke
AT xuxuangao strokedysbiosisindexsdiingutmicrobiomeareassociatedwithbraininjuryandprognosisofstroke
AT xiulizeng strokedysbiosisindexsdiingutmicrobiomeareassociatedwithbraininjuryandprognosisofstroke
AT jiajiazhu strokedysbiosisindexsdiingutmicrobiomeareassociatedwithbraininjuryandprognosisofstroke
AT kaiyuxu strokedysbiosisindexsdiingutmicrobiomeareassociatedwithbraininjuryandprognosisofstroke
AT chuhongtan strokedysbiosisindexsdiingutmicrobiomeareassociatedwithbraininjuryandprognosisofstroke
AT ruotingxu strokedysbiosisindexsdiingutmicrobiomeareassociatedwithbraininjuryandprognosisofstroke
AT qihengwu strokedysbiosisindexsdiingutmicrobiomeareassociatedwithbraininjuryandprognosisofstroke
AT hongweizhou strokedysbiosisindexsdiingutmicrobiomeareassociatedwithbraininjuryandprognosisofstroke
AT yanhe strokedysbiosisindexsdiingutmicrobiomeareassociatedwithbraininjuryandprognosisofstroke
AT jiayin strokedysbiosisindexsdiingutmicrobiomeareassociatedwithbraininjuryandprognosisofstroke