title: Dysbiosis of Gut Microbiota With Reduced Trimethylamine-N-Oxide Level in Patients With Large-Artery Atherosclerotic Stroke or Transient Ischemic Attack.
abstract: BACKGROUND
  Gut microbiota has been suggested to play a role in almost all major diseases including cardio- and cerebrovascular diseases. A possible mechanism is the transformation of dietary choline and l-carnitine into trimethylamine by gut bacteria. This metabolite is further oxidized into trimethylamine-N-oxide (TMAO) in liver and promotes atherogenesis. Nevertheless, little is known about gut microbial diversity and blood TMAO levels in stroke patients.
  
  
  RESULTS
  We performed a case-control study of patients with large-artery atherosclerotic ischemic stroke and transient ischemic attack. TMAO was determined with liquid chromatography tandem mass spectrometry. Gut microbiome was profiled using Illumina sequencing of the 16S rRNA V4 tag. Within the asymptomatic control group, participants with and without carotid atherosclerotic plaques showed similar levels of TMAO without a significant difference in gut microbiota; however, the gut microbiome of stroke and transient ischemic attack patients was clearly different from that of the asymptomatic group. Stroke and transient ischemic attack patients had more opportunistic pathogens, such as Enterobacter, Megasphaera, Oscillibacter, and Desulfovibrio, and fewer commensal or beneficial genera including Bacteroides, Prevotella, and Faecalibacterium. This dysbiosis was correlated with the severity of the disease. The TMAO level in the stroke and transient ischemic attack patients was significantly lower, rather than higher, than that of the asymptomatic group.
  
  
  CONCLUSIONS
  Participants with asymptomatic atherosclerosis did not exhibit an obvious change in gut microbiota and blood TMAO levels; however, stroke and transient ischemic attack patients showed significant dysbiosis of the gut microbiota, and their blood TMAO levels were decreased.
authors.affiliation: Department of Neurology, NanFang Hospital, Southern Medical University, Guangzhou, China (J.Y., S.X.L., G.H.X., J.J.Z., C.Y., Q.C., L.Z., S.Y.P.).
authors.forename: Jia
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Neurology, NanFang Hospital, Southern Medical University, Guangzhou, China (J.Y., S.X.L., G.H.X., J.J.Z., C.Y., Q.C., L.Z., S.Y.P.).
authors.forename: Shuo-Xi
authors.initials: SX
authors.lastname: Liao
authors.affiliation: Department of Environmental Health, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China (Y.H., S.W., F.T.L., H.W.Z.).
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Environmental Health, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China (Y.H., S.W., F.T.L., H.W.Z.).
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurology, NanFang Hospital, Southern Medical University, Guangzhou, China (J.Y., S.X.L., G.H.X., J.J.Z., C.Y., Q.C., L.Z., S.Y.P.).
authors.forename: Geng-Hong
authors.initials: GH
authors.lastname: Xia
authors.affiliation: Department of Environmental Health, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China (Y.H., S.W., F.T.L., H.W.Z.).
authors.forename: Fei-Tong
authors.initials: FT
authors.lastname: Liu
authors.affiliation: Department of Neurology, NanFang Hospital, Southern Medical University, Guangzhou, China (J.Y., S.X.L., G.H.X., J.J.Z., C.Y., Q.C., L.Z., S.Y.P.).
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Zhu
authors.affiliation: Department of Neurology, NanFang Hospital, Southern Medical University, Guangzhou, China (J.Y., S.X.L., G.H.X., J.J.Z., C.Y., Q.C., L.Z., S.Y.P.).
authors.forename: Chao
authors.initials: C
authors.lastname: You
authors.affiliation: Department of Neurology, NanFang Hospital, Southern Medical University, Guangzhou, China (J.Y., S.X.L., G.H.X., J.J.Z., C.Y., Q.C., L.Z., S.Y.P.).
authors.forename: Qiong
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Neurology, NanFang Hospital, Southern Medical University, Guangzhou, China (J.Y., S.X.L., G.H.X., J.J.Z., C.Y., Q.C., L.Z., S.Y.P.).
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Neurology, NanFang Hospital, Southern Medical University, Guangzhou, China (J.Y., S.X.L., G.H.X., J.J.Z., C.Y., Q.C., L.Z., S.Y.P.).
authors.forename: Su-Yue
authors.initials: SY
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China (H.W.Z.) Department of Environmental Health, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China (Y.H., S.W., F.T.L., H.W.Z.).
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Zhou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D058070:Asymptomatic Diseases; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis / Q000382:microbiology*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D015536:Down-Regulation; D064806:Dysbiosis; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D002546:Ischemic Attack, Transient / Q000097:blood / Q000175:diagnosis / Q000382:microbiology*; D008297:Male; D013058:Mass Spectrometry; D008744:Methylamines / Q000097:blood*; D008875:Middle Aged; D021521:Ribotyping; D020521:Stroke / Q000097:blood / Q000175:diagnosis / Q000382:microbiology*
chemical_list: D008744:Methylamines; C005855:trimethyloxamine
keywords: atherosclerosis; gut microbiome; stroke/transient ischemic attack; trimethylamine‐N‐oxide