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1.汕头大学医学院第二附属医院神经内科,汕头 515041
2.云浮市人民医院神经内科,云浮 527300
郑晓红,Email:sophy0323@126.com,研究方向:脑血管病、神经变性病(认知障碍)。
陈 薇,Email:chw7203@126.com。
收稿:2025-06-27,
修回:2025-11-27,
录用:2025-12-15,
纸质出版:2026-04-28
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郑晓红,黄智彦,吴焕泽,等.急性缺血性脑卒中患者口腔菌群的临床特点分析[J].重庆医科大学学报,2026,51(4):467-476.
Zheng Xiaohong,Huang Zhiyan,Wu Huanze,et al.Clinical features of oral flora in patients with acute ischemic stroke[J].Journal of Chongqing Medical University,2026,51(4):467-476.
郑晓红,黄智彦,吴焕泽,等.急性缺血性脑卒中患者口腔菌群的临床特点分析[J].重庆医科大学学报,2026,51(4):467-476. DOI: 10.13406/j.cnki.cyxb.004041.
Zheng Xiaohong,Huang Zhiyan,Wu Huanze,et al.Clinical features of oral flora in patients with acute ischemic stroke[J].Journal of Chongqing Medical University,2026,51(4):467-476. DOI: 10.13406/j.cnki.cyxb.004041.
目的
2
探讨急性缺血性脑卒中(acute ischemic stroke,AIS)患者口腔菌群的特征及其与梗塞面积、预后的关联。
方法
2
纳入2022年2月至2023年6月汕头大学医学院第二附属医院100例AIS患者组成AIS组,以及31例健康对照者(healthy controls,HC)组成HC组。采集口腔黏膜样本,通过太平洋生物科学公司(Pacific Biosciences,PacBio)Sequel Ⅱe平台进行16S核糖体核糖核酸(ribosomal ribonucleic acid,rRNA)全长测序。分析Alpha、Beta多样性、菌群丰度差异及功能预测。AIS患者进一步按梗塞病灶直径(>2 cm为非腔隙性脑梗塞组B组,≤2 cm为腔隙性脑梗塞组S组)和90 d改良 Rankin 量表(modified Rankin scale,mRS)评分(≥3分为预后不良组D1组,<3分为预后良好组D0组)分组比较。
结果
2
菌群多样性:AIS组Faith系统发育多样性指数高于HC组(186.53±28.32 vs. 163.73±37.00,
t
=3.156,
P
=0.003),Beta多样性在AIS组与HC组(
R
2
=0.018,
F
=2.309,
P
=0.001)及B组与S组(
R
2
=0.021,
F
=2.106,
P
=0.001)组间差异有统计学意义。菌群相对丰度:门水平上,与HC组比较,AIS组拟杆菌门(中位数20.31% vs. 11.32%,
U
=1 051.000,
P
=0.007)、螺旋体门(0.51% vs.0.17%,
U
=934.000,
P
<
0.001)等4个菌门显著富集,而明显降低的菌门为变形菌门(13.76% vs. 21.03%,
U
=1 136.000,
P
=0.025)。属水平分析显示,AIS组普雷沃氏菌属(6.23% vs.2.73%,
U
=962.000,
P
=0.001)、乳杆菌属(0.77% vs. 0.15%,
U
=618.000,
P
<
0.001)、密螺旋体属(0.49% vs. 0.15%,
U
=941.000,
P
=0.001)等27个物种相对丰度升高,奈瑟氏菌属(3.22% vs. 6.90%,
U
=987.000,
P
=0.002)相对丰度明显降低。在AIS疾病亚组(D1与D0)比较中,包括韦荣氏球菌属(4.85% vs. 8.55%,
U
=652.000,
P
=0.010)在内的5个物种在D1组富集,而孪生球菌属相对丰度降低(3.51% vs. 2.43%,
U
=690.000,
P
=0.022)。菌群功能预测:与HC组相比,AIS组在核苷酸代谢(8.45% vs. 8.25%,
U
=1 176.000,
P
=0.043)、糖的生物合成与代谢(3.09% vs.2.94%,
U
=1 097.000,
P
=0.014)、细胞生长与死亡(1.12% vs. 1.10%,
U
=1 104.000,
P
=0.016)等6条功能通路富集水平升高;而在氨基酸代谢(12.60% vs. 12.91%,
U
=1 055.000,
P
=0.007)、膜运输(6.99% vs. 7.23%,
U
=1 162.000,
P
=0.036)以及神经退行性疾病(0.41% vs. 0.51%,
U
=1 047.000,
P
=0.006)相关的通路富集水平降低。
结论
2
AIS患者口腔菌群结构、功能与健康人群存在差异,特定菌群丰度变化与不良预后相关,提示口腔菌群可能作为AIS潜在生物标志物及干预靶点。
Objective
2
To investigate the features of oral flora in patients with acute ischemic stroke(AIS) and their association with infarct area and prognosis.
Methods
2
A total of 100 patients with AIS who were treated in The Second Affiliated Hospital of Shantou University Medical College from February 2022 to June 2023 were enrolled as AIS group,and 31 healthy controls were enrolled as HC group. Oral mucosal samples were collected,and Pacific Biosciences(PacBio) Sequel Ⅱe platform was used for full-length 16S ribosomal ribonucleic acid(rRNA) sequencing. Oral flora were analyzed in terms of alpha/beta diversity,abundance,and functional prediction. According to the infarct area,the patients with AIS were further divided into non-lacunar cerebral infarction group(group B witha diameter of the infarct lesion of >2 cm) and lacunar cerebral infarction group(group S with a diameter of the infarct lesion of ≤2 cm),and according to the modified Rankin Scale(mRS) score,they were divided into poor prognosis group (group D1 with an mRS score of ≥3) and good prognosis group(group D0 with an mRS score of <3).
Results
2
As for the diversity of flora,the AIS group had a significantly higher Faith’s phylogenetic diversity index compared with the HC group(186.53±28.32 vs. 163.73±37.00,
t
=3.156,
P
=0.003),and there was a significant difference in beta diversity between the AIS group and the HC group(
R
2
=0.018,
F
=2.309,
P
=0.001) and between groups B and S(
R
2
=0.021,
F
=2.106,
P
=0.001). As for the relative abundance of flora,compared with the HC group at the phylum level,the AIS group had significant enrichment of four phyla,including Bacteroidetes(median:20.31% vs. 11.32%,
U
=1 051.000,
P
=0.007) and Spirochaetes(0.51% vs. 0.17%,
U
=934.000,
P
<
0.001),as well as a significant reduction in the relative abundance of Proteobacter
ia(13.76% vs. 21.03%,
U
=1 136.000,
P
=0.025); at the genus level,the AIS group had significant increases in the relative abundance of 27 species including Prevotella(6.23% vs. 2.73%,
U
=962.000,
P
=0.001),Lactobacillus(0.77% vs. 0.15%,
U
=618.000,
P
<
0.001),and Treponema(0.49% vs. 0.15%,
U
=941.000,
P
=0.001),as well as a significant reduction in the relative abundance of Neisseria(3.22% vs. 6.90%,
U
=987.000,
P
=0.002). Comparison of the AIS disease subgroups(groups D1 and D0) showed that group D1 had significant enrichment of five species including Veillonella(4.85% vs. 8.55%,
U
=652.000,
P
=0.010) and a significant reduction in the relative abundance of Gemella(3.51% vs. 2.43%,
U
=690.000,
P
=0.022). Functional prediction of flora showed that compared with the HC group,the AIS group had significant increases in the enrichment levels of six functional pathways,including nucleotide metabolism(8.45% vs. 8.25%,
U
=1 176.000,
P
=0.043),biosynthesis and metabolism of carbohydrates(3.09% vs. 2.94%,
U
=1 097.000,
P
=0.014),and cell growth and death(1.12% vs. 1.10%,
U
=1 104.000,
P
=0.016),but with significant reductions in the enrichment levels of the pathways associated with amino acid metabolism(12.60% vs. 12.91%,
U
=1 055.000,
P
=0.007),membrane transport(6.99% vs. 7.23%,
U
=1 162.000,
P
=0.036),and neurodegenerative diseases(0.41% vs. 0.51%,
U
=1 047.000,
P
=0.006).
Conclusion
2
There are differences in the structure and function of oral flora between AIS patients and the healthy population,and changes in the abundance of specific flora may be associated with poor prognosis,suggesting that oral flora may be used as potential biomarkers and therapeutic targets for AIS.
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