联合生物信息学和临床回顾性研究评估艰难梭菌毒素A/B对艰难梭菌感染所致腹泻的临床诊断价值OA
Diagnostic Values of Clostridium Difficile Toxin A/B in Diarrhea Caused by Clostridium Difficile Infection:A Com-bined Bioinformatics and Clinical Retrospective Study
目的 结合生物信息学与临床回顾性研究,评估艰难梭菌毒素 A/B 在艰难梭菌感染引起的腹泻中的临床诊断价值.方法 本研究对截至2024 年9 月上传至 NCBI Genome 数据库的艰难梭菌基因组数据进行了系统性分析,涵盖1573 个艰难梭菌的分子分型、进化树构建及耐药基因与毒力基因的分布特征.同时,回顾性分析了699 例轻度及以上腹泻患者的临床数据,探讨 Toxin A/B 检出情况与患者临床症状的相关性.结果 ①基于 1573 个艰难梭菌基因组的 95个序列型,系统进化树分析显示,艰难梭菌可分为5 个主要进化枝.其中,分支1 以序列3 为代表,占比5.85%,包含最多的序列型;分支2 以序列 1 为代表,占比 10.49%;分支 3 包含序列 285,占比 0.03%;分支 4 以序列 39 为代表,占比0.33%;分支5 以序列36 和序列37 为代表,各占比0.13%.②耐药基因分析表明,cdeA 基因在所有序列分型中普遍存在(94.74%),其编码产物与多种药物外排转运蛋白相关.万古霉素耐药基因表现出显著的进化聚集性,涉及所有进化分支,而其他类别的耐药基因进化聚集性较弱.③临床回顾性分析发现,腹泻严重程度与 Toxin A/B 检出率明显呈现正相关(列联相关系数 CC=0.646),高龄患者感染艰难梭菌后表现出更高的毒力,更易导致腹泻程度升高,此外,抗生素使用与 Toxin A/B 检出率和艰难梭菌毒力阳性率呈正相关(CC=0.407).结论 ToxinA/B 的检测结果与患者的腹泻严重程度评分显著相关,进一步证实了 Toxin A/B 在评估艰难梭菌感染后发病中的关键作用.本研究为 Toxin A/B 作为 CDI 诊断的重要生物标志物提供了有力证据,并强调了其在临床诊断流程中的重要性.
Objective To comprehensively evaluate clinical diagnostic values of Clostridioides difficile Toxin A/B in diar-rhea resulting from C.difficile infection through an integrated approach of bioinformatics and retrospective clinical studies.Methods This research systematically examined the genomic data of C.difficile strains uploaded to the NCBI Genome database up to Septem-ber 2024.The analysis included molecular typing,construction of phylogenetic trees,and investigation of the distribution character-istics of resistance and virulence genes among 1,573 C.difficile strains.Moreover,a retrospective analysis was carried out on the clinical data of 699 patients experiencing mild or more severe diarrhea to explore the relationship between the detection of Toxin A/B and the patients'clinical symptoms.Results Based on the 95 sequence types(STs)identified from the 1,573 C.difficile ge-nomes,phylogenetic tree analysis indicated that C.difficile could be classified into five major clades.Clade 1,represented by ST3,accounted for 5.85％ and had the highest number of ST types.Clade2,represented by ST1,made up 10.49％.Clade3 included ST285,with a proportion of 0.03％.Clade 4,represented by ST39,accounted for 0.33％.Clade 5 was represented by ST36 and ST37,each accounting for 0.13％.Resistance gene analysis showed that the cdeA gene was found to be highly prevalent across all ST types,accounting for 94.74％.Its encoded product is associated with various drug-efflux transporters.Vancomycin resistance genes showed significant evolutionary clustering,spanning all evolutionary branches,while other resistance gene categories exhibited weaker clustering.Clinical retrospective clinical analysis found that A significant positive correlation was observed between the se-verity of diarrhea and the detection rate of Toxin A/B(contingency coefficient,CC=0.646).Elderly patients infected with C.diffi-cile showed higher virulence,were more prone to develop severe diarrhea.Additionally,the use of antibiotics was positively correla-ted with the detection rate of Toxin A/B and the positive rate of C.difficile(contingency coefficient,CC=0.407).Conclusion Results of Toxin A/B testing are significantly correlated with the severity score of patients'diarrhea,further validating the crucial role of Toxin A/B in assessing the onset of disease after C.difficile infection.This study provides substantial evidence supporting Toxin A/B as an important biomarker for the diagnosis of Clostridium difficile-associated diarrhea(CDI)and highlights its signifi-cance in the clinical diagnostic process.
郭靓;汪璐;强雪芹
成都市第七人民医院,四川 成都 610041西部战区总医院,四川 成都 610083成都市第七人民医院,四川 成都 610041
医药卫生
艰难梭菌毒素A/B抗生素腹泻
clostridioides difficileToxin A/Bantibioticsdiarrhea
《四川医学》 2026 (4)
403-409,7
成都医学院临床科研基金项目(编号:2020LHJYPJ-03)
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