circRNA/miRNA/mRNA的生物学功能及其对动脉粥样硬化的影响

动脉粥样硬化(As)作为泛血管疾病的慢性动脉壁炎症反应,是导致心脑血管疾病的主要原因之一。目前,越来越多研究表明环状RNA(circRNA)可介导微小RNA(microRNA,miRNA)调控靶基因信使RNA(mRNA)的表达,通过复杂信号传导通路调控内皮细胞(EC)、血管平滑肌细胞(VSMC)和巨噬细胞的增殖、迁移、分化、凋亡及炎症等过程,参与As形成与发展的病理生理过程。文章就circRNA/miRNA/mRNA的生物学功能及其对As的影响进行综合分析,以期为动脉粥样硬化性疾病的诊治提供新思路。     

miRNA与肿瘤转移调控机制的研究进展

转移是恶性肿瘤的基本特征和重要标志,也是癌症患者治疗失败或死亡的首要原因。微小核糖核酸[micro ribonucleic acid(microRNA,miRNA)]是一类具有调控功能的非编码RNA片段,通过调控下游靶基因的转录和翻译,在肿瘤发生发展过程中发挥重要作用。miRNA参与恶性肿瘤侵袭及转移生物学行为中的多个重要环节,阐明肿瘤转移相关miRNA的转移调控机制,将为我们认识肿瘤发生发展提供新视角,给癌症的诊断和治疗带来新突破。该文对miRNA与肿瘤转移调控机制的研究进展进行综述。     

Effect of high-throughput screening of circRNA01724 on a rat model of myocardial ischemia ventricular arrhythmia

BackgroundIt is considered that circRNA can participate in regulating the occurrence and effects of ventricular arrhythmia (VA) through competing endogenous RNA (ceRNA) mechanism, regulating pre-mRNA and regulating parental gene expression. Therefore, we used animal modeling and high-throughput differential screening to screen out circRNA related to VA and study its possible mechanism of action on VA.MethodsThe rat model of myocardial ischemia VA was established. High-throughput screening of the differentiated circRNA was conducted and verified by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot. Lv-circRNA01724 lentivirus was constructed using molecular biology. Primary isolation of the rat cardiomyocytes, hypoxia modeling, Lv-circRNA01724 transfection, mode of action verification, and dual luciferase detection of circRNA01724 and miR-323-5p was performed.ResultsThrough qRT-PCR verification of circRNA01724, circRNA02230, circRNA02088, miR-323-5p, miR-330-5p, and miR-324-3p expressions, circRNA01724 was selected as the research object. Detection by Western blot showed significantly lower Cx43, ZO-1, and α-catenin expressions in rat myocardial tissue in the model group compared with the control group at 1, 7, 14, and 28 days old. On identification of the isolated primary rat cardiomyocytes by immunofluorescence, the α-SMA characteristic protein expression indicated that the isolation was successful. Verification of rat cardiomyocytes transfected with Lv-circRNA01724 suggested overexpression in cells. The miR-323-5p was also highly expressed in the rat cardiomyocyte hypoxia model following Lv-circRNA01724 transfection. Detection by flow cytometry showed that modeling of the transfected Lv-circRNA01724 had a significant increased apoptotic rate. Detection by Western blot showed that modeling of the transfected Lv-circRNA01724 cells had significantly decreased Cx43, ZO-1, and α-catenin compared with the model group.ConclusionsHigh-throughput screening of circRNA01724 can promote the apoptosis of hypoxic cardiomyocytes, which is related to the rat model of myocardial ischemia VA and may be a potential target for the treatment of VA.     

Malignant giant cell tumor of the rib with lung metastasis in a man

Malignant giant cell tumor of bone (MGCTB) accounts for 0.07% of all cases of primary bone tumor. The rarity and complexity of this tumor give rise to some arguments about its histological differentiation, diagnosis, treatment and prognosis. In this paper, we present a 57-year-old man who has a large MGCTB in his rib with lung-targeted metastasis at the time of initial diagnosis. He underwent an operation followed by radiotherapy. The man has been free of recurrence or metastasis for 18 months.     

112例非小细胞肺癌淋巴结转移规律分析

目的分析112例非小细胞肺癌淋巴结的转移规律。方法对112例肺癌患者施行手术切除并行广泛肺门、叶间及纵隔淋巴结清扫术。术后病理资料进行统计分析。结果在共清除898组淋巴结中,单纯N1淋巴结转移率为24.1%,N2(包括N1+N2)淋巴结转移率30.4%。原发肺癌(T)分期T1、T2、T3间淋巴结转移率差异有统计学意义(P0.01)。跳跃式转移占N2转移的35.3%。结论非小细胞肺癌的淋巴结转移与T分期有关,具有较多的跳跃性纵隔淋巴结转移发生,肿瘤部位及肺癌的病理学类型与淋巴结的转移无明显关系。外科治疗中应注意广泛清扫肺内、同侧纵隔淋巴结才有可能达到根治目的。     

Beta-adrenergic signals regulate adipogenesis of mouse mesenchymal stem cells via cAMP/PKA pathway

The adipogenic capacity of mesenchymal stem cells (MSCs) and the involvement of β-adrenergic signals in lipolysis and thermogenesis have been well established. However, little is known about the development of β-adrenergic receptor (β-AR) systems and the role of β-adrenergic signals in adipogenic differentiation of MSCs. In this study, we demonstrated that both the mRNA and protein levels of β2- and β3-AR were up-regulated following adipogenesis of mouse bone marrow derived MSCs. We also established that β-AR agonists negatively while antagonists positively affected MSC adipogenesis. Both the β2- and β3-AR were involved in MSC adipogenesis, with β3-AR being the predominant subtype. The effect of β-ARs on MSC adipogenesis was at least partly mediated via the cAMP/PKA signaling pathway. These findings suggested that MSC is also a target for β-adrenergic regulation, and β-adrenergic signaling (major β3-signaling) plays a role in MSC adipogenesis.     

Reduced expression of circRNA novel_circ_0005280 and its clinical value in the diagnosis of non-small cell lung cancer

BackgroundCircular RNAs (circRNAs) are a class of novel RNAs with important biologic functions. The aberrant expression of circRNAs has been implicated in human diseases; however, the clinical significance of circRNAs in non-small cell lung cancer (NSCLC) is still unclear. The aim of the present study was to evaluate the expression and clinical implications of novel_circ_0005280 in patients with NSCLC.MethodsWe evaluated differential circRNA expression in cancer and adjacent normal tissues from 3 patients with NSCLC via RNA sequencing. Among these circRNAs, 17 and 64 circRNAs showed higher and lower expressions, respectively. Novel_circ_0005280 expression in cancer tissues (n=41) was examined using quantitative real-time polymerase chain reaction, and the results are presented in the form of paired graph and scatter graph and its correlation with clinicopathological features and patient prognosis was analyzed by drawing receiver-operating characteristic (ROC) curve and Kaplan-Meier survival analysis.ResultsNovel_circ_0005280 expression was significantly decreased in NSCLC tumor tissues (n=41, obtained via biopsies), compared with adjacent normal tissues (n=27). Novel_circ_0005280 expression was correlated with tumor diameter and age. The area under the receiver-operating characteristic curve, cutoff, sensitivity, and specificity of novel_circ_0005280 were 0.944, 10.23, 85.2%, and 95.1%, respectively. Low novel_circ_0005280 expression was associated with a worse prognosis.ConclusionsNovel_circ_0005280 may be a useful biomarker for the diagnosis and prognosis of NSCLC.     

Predictive risk factors for lymph node metastasis in patients with small size non-small cell lung cancer

Background

Accurate clinical staging of non-small cell lung cancer (NSCLC) is essential for developing an optimal treatment strategy. This study aimed to determine the predictive risk factors for lymph node metastasis, including both N1 and N2 metastases, in clinical T1aN0 NSCLC patients.

Methods

We retrospectively evaluated clinical T1aN0M0 NSCLC patients who showed no radiologic evidence of lymph node metastasis, and who had undergone surgical pulmonary resection with systematic mediastinal node dissection or sampling at the First Affiliated Hospital of Zhejiang University between January 2011 and June 2013. Univariate and multivariate logistic regression analyses were performed to identify predictive factors for node metastasis.

Results

Pathologically positive lymph nodes were found in 16.2% (51/315) of the patients. Positive N1 nodes were found in 12.4% (39/315) of the patients, and positive N2 nodes were identified in 13.0% (41/315) of the patients. Some 9.2% (29/315) of the patients had both positive N1 and N2 nodes, and 3.8% (12/315) of the patients had nodal skip metastasis. Variables of preoperative radiographic tumor size, non-upper lobe located tumors, high carcinoembryonic antigen (CEA) levels and micropapillary predominant adenocarcinoma (AC) were identified as predictors for positive N1 or N2 node multivariate analysis.

Conclusions

Pathologically positive lymph nodes were common in small size NSCLC patients with clinical negative lymph nodes. Therefore, preoperative staging should be performed more thoroughly to increase accuracy, especially for patients who have the larger size, non-upper lobe located, high CEA level or micropapillary predominant ACs.     

Local ablative therapy of brain metastasis from non-small cell lung cancer: benefits and limitations

Brain metastases (BMs) are the most common intracranial tumors and non-small cell lung cancer (NSCLC) are responsible for BM more than any other solid tumor. Its frequency is increasing due to of the availability of new imaging techniques, earlier diagnosis and improvement in treatment techniques and survival rates. NSCLC patients with BM represent heterogeneous prognostic group. The possibility of better prognostic stratification associated with more systemic therapy options and imaging and radiation technology advances have led to an increment of evaluation and indication of local ablative radiotherapy. The definite increment in quality of life and the potential overall survival (OS) benefit of its indication must be balanced with eventual higher risk of brain disseminated disease when whole brain irradiation is postponed. Therefore, a multidisciplinary evaluation is recommended to refine and personalize the therapeutic approach. The development of clinical nomograms or evaluation of circulating tumor cells/tumoral DNA that predict the survival free of new lesions may be the tools that will warranty further optimization of the treatment of NSCLC patients with BM. In this review, we report the main aspects of diagnosis, prognosis and therapeutic options and dilemmas evolving local ablative radiotherapy essentially based on seminal, updated prospective studies and ongoing trials.     

Quantifying the expression of tumor marker genes in lung squamous cell cancer with RNA sequencing

Background

We measured the expression of some commonly used tumor markers with RNA sequencing (RNA-Seq) to identify any that might be useful for the evaluation of squamous cell lung cancer and identify possible correlations between these tumor markers and any clinical characteristics.

Methods

RNA-Seq was performed on five pairs of squamous-cell lung cancer and normal tissues and another 39 squamous-cell lung cancer tissues obtained by our department between September and December, 2012. The expression of 13 commonly used tumor markers was determined.

Results

All of the patients in our study were male. The expressions of CA125, CYFRA21-1, NSE and SCC increased in tumor samples and there were statistically significant differences between squamous cell lung cancer and normal tissues (P=0.008, P<0.001, P<0.001, P=0.001). The expression of β2M and CA15-3 was reduced in squamous cell carcinoma relative to normal tissues and there was no significant difference in the expression of other tumor markers, including AFP, AFU, CT, FER and HE4.

Conclusions

CA125, CYFRA21-1, NSE and SCC may be appropriate tumor markers for squamous cell lung cancer.     

小鼠口腔癌不同时期淋巴结和骨髓的VEGF表达情况及其微环境对淋巴道转移的影响

目的 探讨小鼠口腔癌不同时期淋巴结和骨髓的血管内皮生长因子(VEGF)表达情况,及其微环境对口腔癌淋巴道转移的影响.方法 选入40只6周龄雄性健康Balb/c小鼠,将其随机分为A、B、C、D、E组,每组8只.采用4-硝基喹啉-1-氧化物(4-NQO)饮水法构建小鼠口腔癌淋巴道转移模型.其中A组为正常小鼠;B组小鼠舌部黏...     

Clinicopathological models for predicting lymph node metastasis in patients with early-stage lung adenocarcinoma: the application of machine learning algorithms

BackgroundLymph node metastasis (LNM) status can be a critical decisive factor for clinical management of lung cancer. Accurately evaluating the risk of LNM during or after the surgery can be helpful for making clinical decisions. This study aims to incorporate clinicopathological characteristics to develop reliable machine learning (ML)-based models for predicting LNM in patients with early-stage lung adenocarcinoma.MethodsA total of 709 lung adenocarcinoma patients with tumor size ≤2 cm were enrolled for analysis and modeling by multiple ML algorithms. The receiver operating characteristic (ROC) curve and decision curve were used for evaluating model’s predictive performance and clinical usefulness. Feature selection based on potential models was performed to identify most-contributed predictive factors.ResultsLNM occurred in 11.3% (80/709) of patients with lung adenocarcinoma. Most models reached high areas under the ROC curve (AUCs) >0.9. In the decision curve, all models performed better than the treat-all and treat-none lines. The random forest classifier (RFC) model, with a minimal number of five variables introduced (including carcinoembryonic antigen, solid component, micropapillary component, lymphovascular invasion and pleural invasion), was identified as the optimal model for predicting LNM, because of its excellent performance in both ROC and decision curves.ConclusionsThe cost-efficient application of RFC model could precisely predict LNM during or after the operation of early-stage adenocarcinomas (sensitivity: 87.5%; specificity: 82.2%). Incorporating clinicopathological characteristics, it is feasible to predict LNM intraoperatively or postoperatively by ML algorithms.     

Prognostic value of thoracic tumor staging and volume parameters in non-small cell lung cancer patients with synchronous solitary bone metastasis

BackgroundNon-small cell lung cancer (NSCLC) patients with synchronous solitary metastasis are a heterogeneous population. The analysis and evaluation of NSCLC patients with synchronous solitary bone metastases by cTN stage (thoracic tumor staging) and volume parameters have not yet been studied. The purpose of this study is to estimate the prognostic value of cTN stage and volume parameters obtained by fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in NSCLC patients with synchronous solitary bone metastasis.MethodsA total of 157 NSCLC patients with synchronous solitary bone metastasis were retrospectively analyzed. Patients’ cTN stage, metabolic tumor volume (MTV) parameters, and clinical data were collected. Kaplan-Meier survival analysis and a Cox regression model were performed to determine the association between each factor and overall survival (OS). Finally, time-dependent receiver operating characteristic (TDROC) curve analysis was used to assess the predictive capacity of the independent prognostic factors.ResultsKaplan-Meier survival analysis showed significant differences between subgroups in terms of cTN stage. The median OS of group I was 44 months, and the 5-year survival rate was 39.6%. In the multivariate Cox regression analysis, cTN stage, MTV of the whole body (MTVwb), and MTV of thorax (MTVtho) were significantly associated with patient OS, even after adjusting for other clinical factors. However, MTV of bone (MTVbon) was not found to be an independent prognostic factor. TDROC curve analysis showed that cTN stage, MTVwb, and MTVtho had good predictive capacity for NSCLC patients with synchronous solitary bone metastasis. Compared with cTN stage and MTVtho, MTVwb had obviously better predictive specificity and sensitivity for the 5-year survival rate [5-year area under the curve (AUC) of MTVwb =0.844 vs. cTN stage (P=0.035) vs. MTVtho (P=0.052)]. The best cutoff value of MTVwb was 33.05.ConclusionsThe results of this study confirmed that cTN stage, MTVwb, and MTVtho were independent prognostic factors of NSCLC patients with synchronous solitary bone metastases. These factors can be used for risk stratification of these patients. TDROC curve analysis indicated that cTN stage, MTVtho, and MTVwb had good performance for survival prediction.     

Lipopolysaccharide and lipoteichoic acid regulate the PI3K/AKT pathway through osteopontin/integrin β3 to promote malignant progression of non-small cell lung cancer

BackgroundLung cancer (LC) is a malignancy with one of the highest mortality rates. Respiratory microbiota is considered to play a key role in the development of LC, but the molecular mechanisms are rarely studied.MethodsWe used lipopolysaccharide (LPS) and lipoteichoic acid (LTA) to study human lung cancer cell lines PC9 and H1299. The gene expression of CXC chemokine ligand (CXCL)1/6, interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The Cell-Counting Kit 8 (CCK-8) was used to analyze cell proliferation. Transwell assays were performed to analyze cell migration ability. Flow cytometry was used to observe cell apoptosis. Western blot and qRT-PCR were used to analyze the expression of secreted phosphoprotein 1 (SPP1), toll-like receptor (TLR)-2/4, and NLR family pyrin domain containing 3 (NLRP3) to determine the mechanism of LPS + LTA. We evaluated the effect of LPS + LTA on cisplatin sensibility by analyzing cell proliferation, apoptosis, and caspase-3/9 expression levels. We observed the proliferation activity, apoptosis, and migration ability of cells in which SPP1 had been transfected small interfering (si) negative control (NC) and integrin β3 siRNA. Then the mRNA expression level and protein expression of PI3K, AKT, and ERK were analyzed. Finally, the nude mouse tumor transplantation model was conducted to verify.ResultsWe studied that in two cell lines, the expression level of inflammatory factors in LPS+LTA group was significantly higher than that in single treatment group (P<0.001). We explored LPS + LTA combined treatment group significantly increased the expression of NLRP3 and genes and proteins. LPS + LTA + Cisplatin group could significantly reduce the inhibitory effect of LPS on cell proliferation (P<0.001), reduce the apoptosis rate (P<0.001) and significantly reduce the expression levels of caspase-3/9 (P<0.001) compared with Cisplatin group. Finally, we verified that LPS and LTA could increase osteopontin (OPN)/integrin β3 expression and activate the PI3K/AKT pathway to promote malignant progression of LC in vitro studies.ConclusionsThis study provides a theoretical basis for further exploration of the influence of lung microbiota on NSCLC and the optimization of LC treatment in the future.     

血清CA125和IL-10水平测定在评估晚期非小细胞肺癌患者预后中的价值

目的探讨血清CA125和IL-10水平测定在评估晚期非小细胞肺癌(NSCLC)患者预后中的价值。方法本文对132例晚期NSCLC患者进行了治疗前后血清CA125和IL-10水平的测定,并与76例良性肺部疾病患者进行了比较性分析,采用受试者工作特征曲线(ROC曲线)分析了CA125和IL-10水平在评估晚期NSCLC患者预后中的价值。结果 132例晚期NSCLC患者(包括51例腺癌、53例鳞癌和28例腺鳞癌)血清CA125和IL-10水平较76例良性肺部疾病患者明显增高(P0.05~0.001)。Ⅳ期和低分化NSCLC患者血清CA125和IL-10增高的病例数较Ⅲa期和高分化患者明显增高(P均0.05)。47例部分缓解(part remission,PR)患者血清CA125和IL-10水平治疗后明显降低、37例疾病进展(progressive disease,PD)患者治疗后血清CA125和IL-10水平仍明显升高、且47例PR患者生存期较37例PD患者明显延长(P均0.05)。ROC曲线分析显示:CA125和IL-10水平评估晚期NSCLC患者预后价值的AUC为0.803和0.764,临界值分别为84.1U/ml和65.2ng/L,敏感度分别为81.5%和77.4%,特异度分别为87.6%和80.1%。结论血清CA125和IL-10水平是评估晚期NSCLC患者预后的有价值指标。     

HMGB1/MMP9在非小细胞肺癌中的表达及临床意义

目的探讨HMGB1和MMP9在NSCLC转移过程中的作用。方法应用免疫组化S-P法检测69例非小细胞肺癌(NSCLC)和20例癌旁组织中HMGB1及MMP9的表达情况,结合临床、病理参数进行统计学分析。结果 1、HMGB1/MMP9二者在NSCLC组织的阳性表达率高于癌旁组织;两组之间差异有统计学意义(P<0.05);2、HMGB1和MMP9在非小细胞肺癌及癌旁组织中表达呈正相关。结论 HMGB1/MMP9联合检测,在NSCLC浸润转移过程中可能起协同作用,可为NSCLC诊断及判断预后提供依据。     

Low expression of long non-coding RNA ARAP1-AS1 can inhibit lung cancer proliferation by inducing G0/G1 cell cycle organization

BackgroundThis paper examines the expression, function, and molecular mechanism of long non-coding ribonucleic acid (lncRNA) ARAP1 antisense RNA 1 (ARAP1-AS1) in lung cancer. Specifically, it aims to clarify the molecular mechanism of lncRNA ARAP1-AS1 that affects the occurrence and development of lung cancer, and provide a theoretical basis and molecular targets for targeted therapy or early diagnosis of lung cancer.MethodsFluorescence quantitative detection of lncRNA ARAP1-AS1 expression in lung cancer tissues and cell lines, and methylthiazolyldiphenyl-tetrazolium (MTT), plate cloning experiment, and flow cytometry were used to detect the effect of knockdown of lncRNA ARAP1-AS1 on cell proliferation, clone formation, and the cell cycle, respectively. Western blotting was used to detect the expression of cell cycle-related proteins as well as the effect of knockdown of lncRNA ARAP1-AS1 on lung cancer. Cell proliferation was assessed by a nude mouse subcutaneous tumor formation experiment.ResultsLncRNA ARAP1-AS1 is highly expressed in lung cancer tissues and cells. Knockdown of LncRNA ARAP1-AS1 can significantly inhibit the proliferation and clonal formation of lung cancer cells and induce G0/G1 cell cycle arrest. Knockdown of ARAP1-AS1 can markedly inhibit the expression of cell cycle-related protein cyclin D1, but has no significant effect on the expression of cyclin-dependent kinase (CDK)4 and CDK6. Furthermore, knockdown of ARAP1-AS1 can also notably inhibit the growth of lung cancer cells and substantially reduce the expression of Ki-67 in tumor-bearing tissues in nude mice.ConclusionsLncRNA ARAP1-AS1 is highly expressed in lung cancer. Knocking down of this gene can significantly inhibit cell proliferation in vitro and in vivo, and can also cause G0/G1 cell cycle arrest by inhibiting the expression of cyclin D1.     

Deleted in liver cancer 2 suppresses cell growth via the regulation of the Raf‐1–ERK1/2–p70S6K signalling pathway

Background: Deleted in liver cancer 2 (DLC2) gene, a putative tumour suppressor gene, encodes a Rho GTPase‐activating protein (RhoGAP) with GAP activity specific for RhoA. It exhibits tumour suppressor functions and inhibits tumour cell proliferation, migration as well as transformation. Aims: In this study, we aimed to investigate the underlying mechanisms of the DLC2 gene in suppressing cell migration and cell growth. HepG2 hepatoma cells were stably transfected with the DLC2γ isoform, which contains the RhoGAP domain. Methods and results: On performing immunofluorescence staining and Western blot analysis, the expression of the focal adhesion protein paxillin was found to be much reduced in DLC2γ‐stable clones. Upon flow cytometric analysis of the cell cycle profiles, the DLC2γ‐stable clones were shown to have a higher population of cells arrested at the G1 phase than the EGFP vector‐stable clone, suggesting that downregulation of RhoA activity in DLC2γ‐stable clones inhibited cell cycle progression. In the DLC2γ‐stable clone, the levels of Raf‐1 and extracellular signal‐regulated kinase (ERK) 1/2 were decreased as compared with those of the parental HepG2, EGFP vector and DLC2γ–GAP defective mutant‐stable clones. Furthermore, the ribosomal kinase p70S6K, a downstream target of ERK1/2, was suppressed in the DLC2‐stable clones. On the contrary, when DLC2 was knocked down by siRNA in HepG2 cells, the expression levels of phospho‐p70S6K and phospho‐ERK1/2 were upregulated. Conclusion: Our data show that DLC2 inhibits the activity of Raf‐1–ERK1/2–p70S6K via its RhoGAP function, resulting in the suppression of cell growth. Further studies on the molecular signalling between DLC2 and p70S6K may provide an insight into its growth suppressor function.     

Compositional and functional alterations of gut microbiota in patients with stroke

Background and aimsThere is accumulating evidence that gut microbiota plays a key role in cardiovascular diseases. Gut bacteria can transform dietary choline, l-carnitine, and trimethylamine N-oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver. However, the alterations of the gut microbiota in large artery atherosclerotic (LAA) stroke and cardioembolic (CE) stroke have been less studied.Methods and resultsWe performed a case–control study in patients with LAA and CE types of strokes. We profiled the gut microbiome using Illumina sequencing of the 16S ribosomal RNA gene (V4–V5 regions), and TMAO was determined via liquid chromatography–tandem mass spectrometry. Our results showed that the TMAO levels in the plasma of patients with LAA and CE strokes were significantly higher than those in controls (LAA stroke, 2931 ± 456.4 ng/mL; CE stroke, 4220 ± 577.6 ng/mL; healthy control, 1663 ± 117.8 ng/mL; adjusted p < 0.05). The TMAO level in the plasma of patients with LAA stroke was positively correlated with the carotid plaque area (rho = 0.333, 95% CI = 0.08–0.55, p = 0.0093). Notably, the composition and the function of gut microbiota in the LAA stroke group were significantly different from those in the control group (FDR-adjusted p-value < 0.05). There was no significant association between gut microbiota and CE stroke in our study.ConclusionThis study provides evidence for significant compositional and functional alterations of the gut microbiome in patients with LAA stroke. Gut microbiota might serve as a potential biomarker for patients with LAA stroke.