[1] Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W, Li X, Wang L, Wang L, Liu Y, Liu J, Zhang M, Qi J, Yu S, Afshin A, Gakidou E, Glenn S, Krish VS, Miller-Petrie MK, Mountjoy-Venning WC, Mullany EC, Redford SB, Liu H, Naghavi M, Hay SI, Wang L, Murray CJL, Liang X. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017:a systematic analysis for the global burden of disease study 2017[J]. Lancet, 2019, 394:1145-1158.
[2] Chinese Stroke Society, Expert Committee on the Management of Post-Stroke Cognitive Disorders. Expert consensus on the management of post-stroke cognitive impairment[J]. Zhongguo Zu Zhong Za Zhi, 2017, 12:519-531.[中国卒中学会,卒中后认知障碍管理专家委员会.卒中 后认知障碍管理专家共识[J].中国卒中杂志, 2017, 12:519-531.]
[3] Merriman NA, Sexton E, McCabe G, Walsh ME, Rohde D, Gorman A, Jeffares I, Donnelly NA, Pender N, Williams DJ, Horgan F, Doyle F, Wren MA, Bennett KE, Hickey A. Addressing cognitive impairment following stroke:systematic review and Meta-analysis of non-randomised controlled studies of psychological interventions[J]. BMJ Open, 2019, 9:e024429.
[4] Kim JY, Kang K, Kang J, Koo J, Kim DH, Kim BJ, Kim WJ, Kim EG, Kim JG, Kim JM, Kim JT, Kim C, Nah HW, Park KY, Park MS, Park JM, Park JH, Park TH, Park HK, Seo WK, Seo JH, Song TJ, Ahn SH, Oh MS, Oh HG, Yu S, Lee KJ, Lee KB, Lee K, Lee SH, Lee SJ, Jang MU, Chung JW, Cho YJ, Choi KH, Choi JC, Hong KS, Hwang YH, Kim SE, Lee JS, Choi J, Kim MS, Kim YJ, Seok J, Jang S, Han S, Han HW, Hong JH, Yun H, Lee J, Bae HJ. Executive summary of stroke statistics in Korea 2018:a report from the epidemiology research council of the Korean stroke society[J]. J Stroke, 2019, 21:42-59.
[5] Narasimhalu K, Ang S, De Silva DA, Wong MC, Chang HM, Chia KS, Auchus AP, Chen CP. The prognostic effects of poststroke cognitive impairment no dementia and domain-specific cognitive impairments in nondisabled ischemic stroke patients[J]. Stroke, 2011, 42:883-888.
[6] Mok VC, Lam BY, Wong A, Ko H, Markus HS, Wong LK. Early-onset and delayed-onset poststroke dementia:revisiting the mechanisms[J]. Nat Rev Neurol, 2017, 13:148-159.
[7] Bordet R, Ihl R, Korczyn AD, Lanza G, Jansa J, Hoerr R, Guekht A. Towards the concept of disease-modifier in post-stroke or vascular cognitive impairment:a consensus report[J]. BMC Med, 2017, 15:107.
[8] Zhang HL, Tan ZJ, Cai GX, Cai Y. The research progress of control technologies for imbalance of intestinal flora[J]. Zhongguo Wei Sheng Tai Xue Za Zhi, 2011, 23:1033-1036.[张 华玲,谭周进,蔡光先,蔡莹.肠道菌群失调调控技术研究进展[J].中国微生态学杂志, 2011, 23:1033-1036.]
[9] Yin J, Liao SX, He Y, Wang S, Xia GH, Liu FT, Zhu JJ, You C, Chen Q, Zhou L, Pan SY, Zhou HW. Dysbiosis of gut microbiota with reduced trimethylamine-N -oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack[J]. J Am Heart Assoc, 2015, 4:e002699.
[10] Larsen N, Vogensen FK, van den Berg FW, Nielsen DS, Andreasen AS, Pedersen BK, Al-Soud WA, Sørensen SJ, Hansen LH, Jakobsen M. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults[J]. PLoS One, 2010, 5:e9085.
[11] Liu Y, Kong C, Gong L, Zhang X, Zhu Y, Wang H, Qu X, Gao R, Yin F, Liu X, Qin H. The association of post-stroke cognitive impairment and gut microbiota and its corresponding metabolites[J]. J Alzheimers Dis, 2020, 73:1455-1466.
[12] Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, Petersen RC, Schneider JA, Tzourio C, Arnett DK, Bennett DA, Chui HC, Higashida RT, Lindquist R, Nilsson PM, Roman GC, Sellke FW, Seshadri S; American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia. Vascular contributions to cognitive impairment and dementia:a statement for healthcare professionals from the American Heart Association/American Stroke Association[J]. Stroke, 2011, 42:2672-2713.
[13] Houlden A, Goldrick M, Brough D, Vizi ES, Lénárt N, Martinecz B, Roberts IS, Denes A. Brain injury induces specific changes in the caecal microbiota of mice via altered autonomic activity and mucoprotein production[J]. Brain Behav Immun, 2016, 57:10-20.
[14] Xia GH, You C, Gao XX, Zeng XL, Zhu JJ, Xu KY, Tan CH, Xu RT, Wu QH, Zhou HW, He Y, Yin J. Stroke Dysbiosis Index (SDI) in gut microbiome are associated with brain injury and prognosis of stroke[J]. Front Neurol, 2019, 10:397.
[15] Benakis C, Poon C, Lane D, Brea D, Sita G, Moore J, Murphy M, Racchumi G, Iadecola C, Anrather J. Distinct commensal bacterial signature in the gut is associated with acute and long-term protection from ischemic stroke[J]. Stroke, 2020, 51:1844-1854.
[16] Chen R, Xu Y, Wu P, Zhou H, Lasanajak Y, Fang Y, Tang L, Ye L, Li X, Cai Z, Zhao J. Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota[J]. Pharmacol Res, 2019, 148:104403.
[17] Wu C, Xue F, Lian Y, Zhang J, Wu D, Xie N, Chang W, Chen F, Wang L, Wei W, Yang K, Zhao W, Wu L, Song H, Ma Q, Ji X. Relationship between elevated plasma trimethylamine N-oxide levels and increased stroke injury[J]. Neurology, 2020, 94:e667-677.
[18] Kim JM, Jung KH, Sohn CH, Moon J, Han MH, Roh JK. Middle cerebral artery plaque and prediction of the infarction pattern[J]. Arch Neurol, 2012, 69:1470-1475.
[19] Deng Y, Wang L, Sun X, Liu L, Zhu M, Wang C, Sui B, Shen M, Gu W, Mo D, Ma N, Song L, Li X, Huo X, Miao Z, Chen D, Gao F. Association between cerebral hypoperfusion and cognitive impairment in patients with chronic vertebra-basilar stenosis[J]. Front Psychiatry, 2018, 9:455.
[20] Pantoni L. Cerebral small vessel disease:from pathogenesis and clinical characteristics to therapeutic challenges[J]. Lancet Neurol, 2010, 9:689-701.
[21] Brandsma E, Kloosterhuis NJ, Koster M, Dekker DC, Gijbels MJJ, van der Velden S, Ríos-Morales M, van Faassen MJR, Loreti MG, de Bruin A, Fu J, Kuipers F, Bakker BM, Westerterp M, de Winther MPJ, Hofker MH, van de Sluis B, Koonen DPY. A proinflammatory gut microbiota increases systemic inflammation and accelerates atherosclerosis[J]. Circ Res, 2019, 124:94-100.
[22] Jonsson AL, Bäckhed F. Role of gut microbiota in atherosclerosis[J]. Nat Rev Cardiol, 2017, 14:79-87.
[23] Koren O, Spor A, Felin J, Fåk F, Stombaugh J, Tremaroli V, Behre CJ, Knight R, Fagerberg B, Ley RE, Bäckhed F. Human oral, gut, and plaque microbiota in patients with atherosclerosis[J]. Proc Natl Acad Sci USA, 2011, 108 Suppl 1:4592-4598.
[24] Stancu CS, Sanda GM, Deleanu M, Sima AV. Probiotics determine hypolipidemic and antioxidant effects in hyperlipidemic hamsters[J]. Mol Nutr Food Res, 2014, 58:559-568.
[25] Fu J, Bonder MJ, Cenit MC, Tigchelaar EF, Maatman A, Dekens JA, Brandsma E, Marczynska J, Imhann F, Weersma RK, Franke L, Poon TW, Xavier RJ, Gevers D, Hofker MH, Wijmenga C, Zhernakova A. The gut microbiome contributes to a substantial proportion of the variation in blood lipids[J]. Circ Res, 2015, 117:817-824.
[26] Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, Wang Z, Li L, Fu X, Wu Y, Mehrabian M, Sartor RB, McIntyre TM, Silverstein RL, Tang WHW, DiDonato JA, Brown JM, Lusis AJ, Hazen SL. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk[J]. Cell, 2016, 165:111-124.
[27] Brunt VE, Gioscia-Ryan RA, Casso AG, VanDongen NS, Ziemba BP, Sapinsley ZJ, Richey JJ, Zigler MC, Neilson AP, Davy KP, Seals DR. Trimethylamine-N-oxide promotes age-related vascular oxidative stress and endothelial dysfunction in mice and healthy humans[J]. Hypertension, 2020, 76:101-112.
[28] Liu W, Wong A, Au L, Yang J, Wang Z, Leung EY, Chen S, Ho CL, Mok VC. Influence of amyloid-β on cognitive decline after stroke/transient ischemic attack:three-year longitudinal study[J]. Stroke, 2015, 46:3074-3080.
[29] Dong DW, Zhang YS, Yang WY, Wang-Qin RQ, Xu AD, Ruan YW. Hyperphosphorylation of tau protein in the ipsilateral thalamus after focal cortical infarction in rats[J]. Brain Res, 2014, 1543:280-289.
[30] Kim H, Seo JS, Lee SY, Ha KT, Choi BT, Shin YI, Ju Yun Y, Shin HK. AIM2 inflammasome contributes to brain injury and chronic post-stroke cognitive impairment in mice[J]. Brain Behav Immun, 2020, 87:765-776.
[31] Li B, He Y, Ma J, Huang P, Du J, Cao L, Wang Y, Xiao Q, Tang H, Chen S. Mild cognitive impairment has similar alterations as Alzheimer's disease in gut microbiota[J]. Alzheimers Dement, 2019, 15:1357-1366.
[32] Zhan X, Stamova B, Jin LW, DeCarli C, Phinney B, Sharp FR. Gram-negative bacterial molecules associate with Alzheimer disease pathology[J]. Neurology, 2016, 87:2324-2332.
[33] Erickson MA, Hartvigson PE, Morofuji Y, Owen JB, Butterfield DA, Banks WA. Lipopolysaccharide impairs amyloid β efflux from brain:altered vascular sequestration, cerebrospinal fluid reabsorption, peripheral clearance and transporter function at the blood-brain barrier[J]. J Neuroinflammation, 2012, 9:150.
[34] Kim MS, Kim Y, Choi H, Kim W, Park S, Lee D, Kim DK, Kim HJ, Choi H, Hyun DW, Lee JY, Choi EY, Lee DS, Bae JW, Mook-Jung I. Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer's disease animal model[J]. Gut, 2020, 69:283-294.
[35] Zhan X, Cox C, Ander BP, Liu D, Stamova B, Jin LW, Jickling GC, Sharp FR. Inflammation combined with ischemia produces myelin injury and plaque-like aggregates of myelin, amyloid-β and AβPP in adult rat brain[J]. J Alzheimers Dis, 2015, 46:507-523.
[36] Bowman GL, Dayon L, Kirkland R, Wojcik J, Peyratout G, Severin IC, Henry H, Oikonomidi A, Migliavacca E, Bacher M, Popp J. Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults[J]. Alzheimers Dement, 2018, 14:1640-1650.
[37] Nation DA, Sweeney MD, Montagne A, Sagare AP, D'Orazio LM, Pachicano M, Sepehrband F, Nelson AR, Buennagel DP, Harrington MG, Benzinger TLS, Fagan AM, Ringman JM, Schneider LS, Morris JC, Chui HC, Law M, Toga AW, Zlokovic BV. Blood-brain barrier breakdown is an early biomarker of human cognitive dysfunction[J]. Nat Med, 2019, 25:270-276.
[38] Montagne A, Nation DA, Sagare AP, Barisano G, Sweeney MD, Chakhoyan A, Pachicano M, Joe E, Nelson AR, D'Orazio LM, Buennagel DP, Harrington MG, Benzinger TLS, Fagan AM, Ringman JM, Schneider LS, Morris JC, Reiman EM, Caselli RJ, Chui HC, Tcw J, Chen Y, Pa J, Conti PS, Law M, Toga AW, Zlokovic BV. APOE4 leads to blood-brain barrier dysfunction predicting cognitive decline[J]. Nature, 2020, 581:71-76.
[39] Yang Y, Rosenberg GA. Blood-brain barrier breakdown in acute and chronic cerebrovascular disease[J]. Stroke, 2011, 42:3323-3328.
[40] Braniste V, Al-Asmakh M, Kowal C, Anuar F, Abbaspour A, Tóth M, Korecka A, Bakocevic N, Ng LG, Kundu P, Gulyás B, Halldin C, Hultenby K, Nilsson H, Hebert H, Volpe BT, Diamond B, Pettersson S. The gut microbiota influences blood-brain barrier permeability in mice[J]. Sci Transl Med, 2014, 6:263ra158.
[41] Shi K, Tian DC, Li ZG, Ducruet AF, Lawton MT, Shi FD. Global brain inflammation in stroke[J]. Lancet Neurol, 2019, 18:1058-1066.
[42] Zhang X, Bi X. Post-stroke cognitive impairment:a review focusing on molecular biomarkers[J]. J Mol Neurosci, 2020, 70:1244-1254.
[43] Chen Y, Liang J, Ouyang F, Chen X, Lu T, Jiang Z, Li J, Li Y, Zeng J. Persistence of gut microbiota dysbiosis and chronic systemic inflammation after cerebral infarction in cynomolgus monkeys[J]. Front Neurol, 2019, 10:661.
[44] Benakis C, Brea D, Caballero S, Faraco G, Moore J, Murphy M, Sita G, Racchumi G, Ling L, Pamer EG, Iadecola C, Anrather J. Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδT cells[J]. Nat Med, 2016, 22:516-523.
[45] Sadler R, Singh V, Benakis C, Garzetti D, Brea D, Stecher B, Anrather J, Liesz A. Microbiota differences between commercial breeders impacts the post-stroke immune response[J]. Brain Behav Immun, 2017, 66:23-30.
[46] Banks WA, Gray AM, Erickson MA, Salameh TS, Damodarasamy M, Sheibani N, Meabon JS, Wing EE, Morofuji Y, Cook DG, Reed MJ. Lipopolysaccharide-induced blood-brain barrier disruption:roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit[J]. J Neuroinflammation, 2015, 12:223.
[47] Meng F, Li N, Li D, Song B, Li L. The presence of elevated circulating trimethylamine N-oxide exaggerates postoperative cognitive dysfunction in aged rats[J]. Behav Brain Res, 2019, 368:111902.
[48] Kellar D, Craft S. Brain insulin resistance in Alzheimer's disease and related disorders:mechanisms and therapeutic approaches[J]. Lancet Neurol, 2020, 19:758-766.
[49] Wu H, Tremaroli V, Schmidt C, Lundqvist A, Olsson LM, Krämer M, Gummesson A, Perkins R, Bergström G, Bäckhed F. The gut microbiota in prediabetes and diabetes:a population-based cross-sectional study[J]. Cell Metab, 2020, 32:379-390.
[50] Pedersen HK, Gudmundsdottir V, Nielsen HB, Hyotylainen T, Nielsen T, Jensen BA, Forslund K, Hildebrand F, Prifti E, Falony G, Le Chatelier E, Levenez F, Doré J, Mattila I, Plichta DR, Pöhö P, Hellgren LI, Arumugam M, Sunagawa S, Vieira-Silva S, Jørgensen T, Holm JB, Trošt K; MetaHIT Consortium; Kristiansen K, Brix S, Raes J, Wang J, Hansen T, Bork P, Brunak S, Oresic M, Ehrlich SD, Pedersen O. Human gut microbes impact host serum metabolome and insulin sensitivity[J]. Nature, 2016, 535:376-381.
[51] Liu Z, Dai X, Zhang H, Shi R, Hui Y, Jin X, Zhang W, Wang L, Wang Q, Wang D, Wang J, Tan X, Ren B, Liu X, Zhao T, Wang J, Pan J, Yuan T, Chu C, Lan L, Yin F, Cadenas E, Shi L, Zhao S, Liu X. Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment[J]. Nat Commun, 2020, 11:855.
[52] Hang CH, Shi JX, Li JS, Wu W, Yin HX. Alterations of intestinal mucosa structure and barrier function following traumatic brain injury in rats[J]. World J Gastroenterol, 2003, 9:2776-2781.
[53] Stanley D, Mason LJ, Mackin KE, Srikhanta YN, Lyras D, Prakash MD, Nurgali K, Venegas A, Hill MD, Moore RJ, Wong CH. Translocation and dissemination of commensal bacteria in post-stroke infection[J]. Nat Med, 2016, 22:1277-1284.
[54] Tascilar N, Irkorucu O, Tascilar O, Comert F, Eroglu O, Bahadir B, Cakmak GK, Ankarali H, Sayan H. Bacterial translocation in experimental stroke:what happens to the gut barrier[J]? Bratisl Lek Listy, 2010, 111:194-199.
[55] Xu J, Wang YL, Wang YJ. Gut microbiome and ischemic stroke[J]. Zhongguo Zu Zhong Za Zhi, 2017, 12:179-182.[许杰,王伊龙,王拥军.肠道菌群与缺血性卒中[J].中国卒 中杂志, 2017, 12:179-182.]
[56] Singh V, Roth S, Llovera G, Sadler R, Garzetti D, Stecher B, Dichgans M, Liesz A. Microbiota dysbiosis controls the neuroinflammatory response after stroke[J]. J Neurosci, 2016, 36:7428-7440.
[57] Winek K, Engel O, Koduah P, Heimesaat MM, Fischer A, Bereswill S, Dames C, Kershaw O, Gruber AD, Curato C, Oyama N, Meisel C, Meisel A, Dirnagl U. Depletion of cultivatable gut microbiota by broad-spectrum antibiotic pretreatment worsens outcome after murine stroke[J]. Stroke, 2016, 47:1354-1363.
[58] Zhu C, Li G, Lv Z, Li J, Wang X, Kang J, Zhan C. Association of plasma trimethylamine-N-oxide levels with post-stroke cognitive impairment:a 1-year longitudinal study[J]. Neurol Sci, 2020, 41:57-63.
[59] Yamashiro K, Tanaka R, Urabe T, Ueno Y, Yamashiro Y, Nomoto K, Takahashi T, Tsuji H, Asahara T, Hattori N. Gut dysbiosis is associated with metabolism and systemic inflammation in patients with ischemic stroke[J]. PLoS One, 2017, 12:e0171521.