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Cited by 670Gut microbiota and healthOral microbiology and periodontitis researchAbdominal vascular conditions and treatments

Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack

Open access
Yin, Jia, Liao, Shuo‐Xi, He, Yan, Wang, Shan, Xia, Geng‐Hong, Liu, Fei‐Tong, Zhu, Jia‐Jia, You, Chao +4 more·2015·Journal of the American Heart Association
DOI 10.1161/jaha.115.002699PMC PMC4845212
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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. Methods and 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.

AI snapshot

Written from the paper’s full text.

TL;DR

In a Chinese case-control study, large-artery atherosclerotic stroke/TIA patients showed gut microbiota dysbiosis and significantly lower blood TMAO than asymptomatic controls. Asymptomatic participants with carotid atherosclerosis did not show clear gut microbiota or TMAO differences from those without.

Key findings

  • Stroke/TIA patients had a distinct gut microbiome from asymptomatic controls, with more opportunistic pathogens such as *Enterobacter*, *Megasphaera*, *Oscillibacter*, and *Desulfovibrio*, and fewer commensal/beneficial genera including *Bacteroides*, *Prevotella*, and *Faecalibacterium*. LEfSe also showed increased Proteobacteria and reduced *Bacteroides*, *Prevotella*, and *Faecalibacterium* in patients.
  • Within asymptomatic controls, the non-AS, IMT, and AS subgroups showed no significant TMAO difference (median TMAO 2.68, 2.63, and 2.92 μmol/L, respectively; P=0.999) and no obvious gut microbiota grouping by PCoA.
  • TMAO was significantly lower in stroke/TIA patients than in asymptomatic controls (P<0.001); the text reports patient average and median TMAO levels of 2.68 and 1.91 μmol/L, respectively.
  • Dysbiosis correlated with stroke severity: severe stroke (NIHSS >4) differed from mild stroke (NIHSS ≤4) in phylogenetic diversity (P=0.014) and overall microbiota by Adonis (P=0.034), with Proteobacteria more abundant and *Bacteroides* depleted in severe stroke.

Methods

  • Case-control study conducted February 2014–February 2015 at Nanfang Hospital, southern China. It recruited 322 large-artery atherosclerotic ischemic stroke/TIA patients and 231 asymptomatic controls for blood samples; fecal samples were available from 141 patients and 97 controls by the text (Table 1 lists 94 controls).
  • Plasma TMAO was measured by stable isotope dilution liquid chromatography tandem mass spectrometry. Gut microbiome was profiled by Illumina MiSeq sequencing of the 16S rRNA V4 region, with QIIME, PCoA, random forest classification, and LEfSe analyses.
  • Statistical comparisons used Wilcoxon rank sum, Kruskal–Wallis with Nemenyi pairwise tests, chi-square, and Adonis; P<0.05 was considered significant.

Limitations

  • The paper states that patients and controls were not well balanced for age and sex; although 47 age- and sex-matched pairs still separated by microbiota, the original imbalance remains. It also states that only 9 TIA patients were enrolled, so the negative stroke-vs-TIA comparison needs larger studies.
  • The paper states that all samples came from stroke inpatients, so it cannot determine whether gut microbiota changes or lower TMAO occurred before stroke/TIA or were caused by the event/treatment; earliest samples were about 14 hours after the event, with too few early samples for analysis.
  • Evident from the text: Table 1’s TMAO row appears inconsistent with the abstract/text direction of lower TMAO in patients, and the control fecal sample count differs between the text (97) and Table 1 (94).

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1161/jaha.115.002699

Cites

23 of 23 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 20 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Within the asymptomatic control group, participants with and without carotid atherosclerotic plaques showed similar levels of TMAO.

    “Within the asymptomatic control group, participants with and without carotid atherosclerotic plaques showed similar levels of TMAO without a significant difference in gut microbiota”
    • Also stated in: § Results · plain
      “No significant difference was observed for the TMAO levels among the 3 groups (Figure 1A)”
    • Also stated in: § Results · plain
      “TMAO, μmol/L | 2.68 (3.50) | 2.63 (3.63) | 2.92 (3.35) | 0.999”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The observed differences in gut microbiota and TMAO between stroke/TIA patients and controls are not due to differences in age, sex, or comorbidities (e.g., diabetes, hypertension) between the groups.
  • Findingown data

    The effect of initial versus recurrent stroke on gut microbiota was very limited according to alpha- and beta-diversity analyses.

    “We also tested whether the gut microbiota of initial stroke patients differed from that of recurrent stroke patients, and the results showed that this effect was very limited, according to α‐ and β‐diversity analyses (Figure 7D through 7F).”
    Quote in the paperNot a substantial claim
  • Findingown data

    The gut microbiome of stroke and TIA patients is clearly different from that of asymptomatic controls.

    “the gut microbiome of stroke and transient ischemic attack patients was clearly different from that of the asymptomatic group”
    • Also stated in: § Results · boosted
      “the stroke and TIA patients showed clearly different gut microbiota than that of asymptomatic controls”
    • Also stated in: § Results · hedged
      “The difference of the microbiome communities between the 2 groups could be observed using both traditional PCoA (Figure 4A) and machine learning with the random forest method (Figure 4B).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The observed differences in gut microbiota and TMAO between stroke/TIA patients and controls are not due to differences in age, sex, or comorbidities (e.g., diabetes, hypertension) between the groups.
    • Rests on an assumption: The gut microbiota composition from a single fecal sample is representative of the participant's gut microbiota at the time relevant to stroke/TIA.
  • Findingown data

    The alpha-diversity of severe stroke patients (NIHSS score >4) was higher than that of mild stroke patients (NIHSS score ≤4) based on phylogenetic diversity whole tree (23.54 versus 26.47, P=0.014).

    “The α‐diversity of severe stroke patients (NIHSS score >4) was higher than that of mild stroke patients (NIHSS score ≤4) based on phylogenetic diversity whole tree (23.54 versus 26.47, P=0.014) (Figure 8A and 8B).”
    Quote in the paperNot a substantial claim
  • Findingown data

    There was no difference in gut microbiota between samples collected within 24 hours after admission and those collected within 24 to 48 hours, according to alpha- and beta-diversity analyses.

    “According to the α‐ and β‐diversity analyses, there was no difference between the 2 groups (Figure 5), indicating that those changes happened earlier than our first sampling time.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 12
  • May combine two claims. 12
  • The quote only partly states this claim. 3

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The gut microbiome samples can be classified into 3 enterotypes dominated by Bacteroides, Prevotella, and others (mainly Roseburia and Blautia).

    “The gut microbiome samples could be classified into 3 enterotypes, which were dominated by Bacteroides, Prevotella, and others (mainly Roseburia and Blautia in the present study) (Figure 1B).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The gut microbiota composition from a single fecal sample is representative of the participant's gut microbiota at the time relevant to stroke/TIA.

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    The α-diversity of gut microbiota is greater in stroke/TIA patients than in controls for Chao1, observed species, and phylogenetic diversity whole tree.

    “Chao1, observed species, and phylogenetic diversity whole tree reached statistical significance using the Wilcoxon rank sum test”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The observed differences in gut microbiota and TMAO between stroke/TIA patients and controls are not due to differences in age, sex, or comorbidities (e.g., diabetes, hypertension) between the groups.
    • Rests on an assumption: The gut microbiota composition from a single fecal sample is representative of the participant's gut microbiota at the time relevant to stroke/TIA.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). May combine two claims. The quote only partly states this claim.

    Findingown data

    The average TMAO level in the asymptomatic control group was ≈4.14 μmol/L, with a median of 2.71 μmol/L.

    “the average level of the 3 groups was ≈4.14 μmol/L, with a median value of 2.71 μmol/L”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Samples of severe stroke patients tended to be located in the left region of PCoA, whereas those of mild stroke patients tended to be located in the right region.

    “we observed that samples of severe stroke patients tended to be located in the left region of PCoA, whereas those of mild stroke patients tended to be located in the right region (Figure 8C).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The average and median TMAO levels of stroke/TIA patients were 2.68 μmol/L and 1.91 μmol/L, respectively.

    “The average and median TMAO levels of stroke/TIA patients were only 2.68 μmol/L and 1.91 μmol/L, respectively, which were comparable to quartile 1 in a US cohort.5”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    In our Chinese population, asymptomatic atherosclerotic patients had gut microbiota similar to controls, consistent with a US report.

    “It has been reported, using pyrosequencing of 16S rRNA tags, that atherosclerotic patients in the United States had similar gut microbiota to that of controls,22 and our present results from a Chinese population are consistent with that report.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] 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. Proc Natl Acad Sci USA. 2011; 108(suppl 1): 4592– 4598. 20937873 PMC3063583 source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Study design and conductown data

    Patients and controls differed significantly in sex, age, BMI, history of diabetes, hypertension, and several blood lipids and glucose.

    “Male, n (%) | 220 (68.3) | 130 (56.3) | 0.004”
    • Also stated in: § Results · plain
      “Age, y | 61 (19) | 56 (11) | <0.001”
    • Also stated in: § Results · plain
      “History of diabetes, n (%) | 125 (38.8) | 20 (8.66) | <0.001”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    None of the tested indices passed the Shapiro-Wilk normality test and Bartlett test, so Wilcoxon rank sum or Kruskal-Wallis tests were used.

    “None of the tested indices in the present study passed the Shapiro–Wilk normality test and the Bartlett test of homogeneity of variances at the same time; therefore, we used the Wilcoxon rank sum test or Kruskal–Wallis rank sum test (Nemenyi test for multiple pairwise comparisons) to compare ≥2 groups, respectively, in case of false‐positive statistical significance.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Symptomatic atherosclerosis is associated with an altered gut microbiome.

    “a metagenomic study suggested that symptomatic atherosclerosis was associated with an altered gut microbiome.8”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Karlsson FH, Fak F, Nookaew I, Tremaroli V, Fagerberg B, Petranovic D, Bäckhed F, Nielsen J. Symptomatic atherosclerosis is associated with an altered gut metagenome. Nat Commun. 2012; 3: 1245. 23212374 PMC3538954 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Random forest classification models were trained with 10-fold cross-validation and optimized using AUC.

    “Training was achieved through 10‐fold cross‐validation and optimized using the area under the curve derived from receiver operating characteristic analysis.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Only 9 TIA patients were enrolled in this study.

    “only 9 TIA patients were enrolled in this study”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The earliest samples were approximately 14 hours from the event, and there were too few early-stage samples to find significant differences with later samples.

    “our earliest samples were ≈14 hours from the event, and there were too few early stage samples to find any significant differences with those collected later.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Asymptomatic atherosclerosis is not associated with an obvious change in gut microbiota or blood TMAO levels.

    “Participants with asymptomatic atherosclerosis did not exhibit an obvious change in gut microbiota and blood TMAO levels”
    • Also stated in: § Results · hedged
      “All of these analyses suggested that atherosclerosis was not related to a significantly different gut microbiome or blood TMAO level within the asymptomatic group.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The observed differences in gut microbiota and TMAO between stroke/TIA patients and controls are not due to differences in age, sex, or comorbidities (e.g., diabetes, hypertension) between the groups.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Blood TMAO level is positively correlated with long-term mortality risk in patients with atherosclerosis, heart failure, and chronic kidney disease.

    “The blood TMAO level has been reported to be positively correlated with long‐term mortality risk in patients with atherosclerosis, heart failure, and chronic kidney disease.5, 6, 7”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [5] Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of L‐carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013; 19: 576– 585. 23563705 PMC3650111 source

      Not checked in the free run.

    • cites [6] Tang WH, Wang Z, Fan Y, Levison B, Hazen JE, Donahue LM, Wu Y, Hazen SL. Prognostic value of elevated levels of intestinal microbe‐generated metabolite trimethylamine‐N‐oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol. 2014; 64: 1908– 1914. 25444145 PMC4254529 source

      Not checked in the free run.

    • cites [7] Tang WH, Wang Z, Kennedy DJ, Wu Y, Buffa JA, Agatisa‐Boyle B, Li XS, Levison BS, Hazen SL. Gut microbiota‐dependent trimethylamine N‐oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015; 116: 448– 455. 25599331 PMC4312512 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    TMAO promotes atherogenesis partly by promoting the formation of foam cells from macrophages.

    “a metabolite that could promote atherogenesis partly by promoting the formation of foam cells from macrophages.4, 5”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013; 368: 1575– 1584. 23614584 PMC3701945 source

      Not checked in the free run.

    • cites [5] Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of L‐carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013; 19: 576– 585. 23563705 PMC3650111 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The study did not use an age- and sex-matching strategy in selecting controls and patients.

    “We did not use an age‐ and sex‐matching strategy in our selection of controls and patients but set the age range from 18 to 80 years.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Faecalibacterium is a critical butyrate acid-producing beneficial bacterium that is reduced in many diseases.

    “In particular, Faecalibacterium has been widely recognized as a critical butyrate acid–producing beneficial bacterium that is reduced in many diseases.2, 3, 23”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [2] Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, Liang S, Zhang W, Guan Y, Shen D, Peng Y, Zhang D, Jie Z, Wu W, Qin Y, Xue W, Li J, Han L, Lu D, Wu P, Dai Y, Sun X, Li Z, Tang A, Zhong S, Li X, Chen W, Xu R, Wang M, Feng Q, Gong M, Yu J, Zhang Y, Zhang M, Hansen T, Sanchez G, Raes J, Falony G, Okuda S, Almeida M, LeChatelier E, Renault P, Pons N, Batto JM, Zhang Z, Chen H, Yang R, Zheng W, Li S, Yang H, Wang J, Ehrlich SD, Nielsen R, Pedersen O, Kristiansen K, Wang J. A metagenome‐wide association study of gut microbiota in type 2 diabetes. Nature. 2012; 490: 55– 60. 23023125 source

      Not checked in the free run.

    • cites [3] Abu‐Shanab A, Quigley EM. The role of the gut microbiota in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol. 2010; 12: 691– 701. 21045794

      Not checked in the free run.

    • cites [23] Barcenilla A, Pryde SE, Martin JC, Duncan SH, Stewart CS, Henderson C, Flint HJ. Phylogenetic relationships of butyrate‐producing bacteria from the human gut. Appl Environ Microbiol. 2000; 66: 1654– 1661. 10742256 PMC92037

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Many cohort studies have suggested that an increased number of adverse outcomes are associated with high TMAO levels.

    “many cohort studies have suggested that an increased number of adverse outcomes are associated with high TMAO levels,4, 5, 6, 7”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [4] Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013; 368: 1575– 1584. 23614584 PMC3701945 source

      Not checked in the free run.

    • cites [5] Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of L‐carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013; 19: 576– 585. 23563705 PMC3650111 source

      Not checked in the free run.

    • cites [6] Tang WH, Wang Z, Fan Y, Levison B, Hazen JE, Donahue LM, Wu Y, Hazen SL. Prognostic value of elevated levels of intestinal microbe‐generated metabolite trimethylamine‐N‐oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol. 2014; 64: 1908– 1914. 25444145 PMC4254529 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    TMAO level has been suggested to be involved in atherosclerosis.

    “Although the TMAO level has been suggested to be involved in atherosclerosis,4, 5”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [4] Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013; 368: 1575– 1584. 23614584 PMC3701945 source

      Not checked in the free run.

    • cites [5] Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of L‐carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013; 19: 576– 585. 23563705 PMC3650111 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Gut microbiota changes are involved in the onset or even the severity of stroke.

    “These findings indicate that gut microbiota changes are involved in the onset or even the severity of stroke.”
    Quote in the paperSubstantial claim
20 of 20

  • The authors state this as an assumption.

    Little is known about gut microbial diversity and blood TMAO levels in stroke patients.

    “Nevertheless, little is known about gut microbial diversity and blood TMAO levels in stroke patients.”
    “these diseases have rarely been examined with respect to TMAO level and gut microbiota.”

  • The paper relies on this without support.

    The observed differences in gut microbiota and TMAO between stroke/TIA patients and controls are not due to differences in age, sex, or comorbidities (e.g., diabetes, hypertension) between the groups.

    “stroke and transient ischemic attack patients showed significant dysbiosis of the gut microbiota”
    “Male, n (%) | 220 (68.3) | 130 (56.3) | 0.004”

  • The paper relies on this without support.

    The gut microbiota composition from a single fecal sample is representative of the participant's gut microbiota at the time relevant to stroke/TIA.

    “their first available fecal samples within 48 hours after admission were collected”

  • The paper relies on this without support.

    The blood TMAO level measured within 24 hours after admission reflects the patient's usual TMAO level and is not substantially altered by acute stroke.

    “The first fasting blood samples were drawn from all participants within 24 hours after admission”

  • The paper relies on this without support.

    No reports have examined the increase in TMAO levels in asymptomatic atherosclerosis patients.

    “no reports have examined the increase in TMAO levels in asymptomatic atherosclerosis patients.”

  • The paper relies on this without support.

    The three major depleted genera (Bacteroides, Prevotella, and Faecalibacterium) are major commensal or beneficial microbes.

    “the 3 major depleted genera in the patient groups, namely, Bacteroides, Prevotella, and Faecalibacterium, are major commensal or beneficial microbes.”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In a case-control study of patients with large-artery atherosclerotic ischemic stroke and transient ischemic attack, asymptomatic atherosclerosis participants did not exhibit an obvious change in gut microbiota and blood TMAO levels; stroke and transient ischemic attack patients showed significant dysbiosis and their blood TMAO levels were decreased.

    “In a case-control study of patients with large-artery atherosclerotic ischemic stroke and transient ischemic attack, 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 [36].”

    From Trimethylamine N-oxide: the good, the bad and the unknown. (2016) · cites this paper as [36]

  • Bacteroides abundance is decreased in patients with atherosclerotic ischemic stroke and transient ischemic attack.

    “Moreover, Bacteroides abundance was found to be decreased in patients with atherosclerotic ischemic stroke and transient ischemic attack.10”

    From <i>Bacteroides vulgatus</i> and <i>Bacteroides dorei</i> Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis (2018) · cites this paper as [10]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Table 1 reverses the reported TMAO difference

    Major

    Table 1 reports a higher median TMAO level for patients than controls (2.70 versus 1.91 μmol/L). The paper repeatedly concludes that patients had lower TMAO levels than controls.

  • Patient TMAO median differs between the table and text

    Major

    The text gives the patient median as 1.91 μmol/L, whereas Table 1 gives it as 2.70 μmol/L. The text's patient median instead matches the table's control median.

  • Severe-stroke diversity is described as higher but listed first as lower

    Major

    The sentence says diversity was higher in severe than mild stroke, but its severe-versus-mild values are presented as 23.54 versus 26.47, respectively.

  • Control fecal-sample counts disagree

    Minor

    The Results state that 97 controls provided fecal samples, but Table 1 lists 94.

4 of 4

Cites

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Related

Authors
Yin, J., Liao, S., He, Y., Wang, S., Xia, G., Liu, F., Zhu, J., You, C., Chen, Q., Zhou, L., Pan, S., & Zhou, H.
Affiliations
  • Nanfang Hospital (CN)
  • Southern Medical University (CN)
  • Department of Neurology, NanFang Hospital, Southern Medical University, Guangzhou, China
  • Department of Environmental Health, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, China
  • State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China
ORCID
Venue
Journal of the American Heart Association
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2015-10-29
Volume
4
Issue
11
ISSN
2047-9980 (ISSN-L)
DOI
10.1161/jaha.115.002699
PMC
PMC4845212
OpenAlex
W2178133650
Semantic Scholar
e22153ff5a5f849aa7f5c6438beb6f42c91f837e
Cited by
669
References
23
Citations by year
2026: 35 · 2025: 72 · 2024: 71 · 2023: 96 · 2022: 117 · 2021: 76 · 2020: 78 · 2019: 57 · 2018: 34 · 2017: 20 · 2016: 13
FWCI
9.69
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Journal of the American Heart Association (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (31270152)
  • Natural Science Foundation of Guangdong Province
  • Guangzhou Municipal Science and Technology Project
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
  • Health Sciences › Medicine › Surgery › Abdominal vascular conditions and treatments
Keywords
gut dysbiosis, trimethylamine N-oxide, large artery atherosclerotic stroke, transient ischemic attack, ischemic stroke, carotid plaque, opportunistic pathogens, Enterobacter, Megasphaera, Oscillibacter, Bacteroides, Prevotella, Faecalibacterium, atherogenesis, disease severity
MeSH terms
Gastrointestinal Microbiome, Aged, Aged, 80 and over, Bacteria, Carotid Artery Diseases, Ischemic Attack, Transient, Chromatography, Liquid, Feces, Female, Humans, Intestines, Male, Methylamines, Middle Aged, Mass Spectrometry, Down-Regulation, Case-Control Studies, Stroke, Ribotyping, Asymptomatic Diseases, Dysbiosis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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