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基于16S rRNA基因测序的脓毒症患者肠道菌群特征及其与预后的关联性研究▲
Gut microbiota characteristics in sepsis patients based on 16S rRNA gene sequencing and their associations with prognosis

内科 页码:350-357

作者机构:广西柳州市人民医院重症医学科,柳州市 545006

基金信息:广西壮族自治区卫生健康委员会自筹经费科研课题(Z20200089);柳州市科技计划项目(2022SB008);广西壮族自治区卫生健康委员会医疗卫生重点学科建设项目(2019-19) 通信作者:吕光宇

DOI:10.16121/j.cnki.cn45-1347/r.2025.04.02

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目的 基于16S rRNA基因测序技术,探讨脓毒症患者肠道菌群的结构与多样性特征,并初步探索其与患者院内预后的关联性。方法 采用前瞻性研究方法,收集50例脓毒症患者(脓毒症组)入院2 d内的粪便样本及10例健康志愿者(健康组)的粪便样本。对粪便菌群16S rRNA基因V3~V4区进行测序,进行生物信息学分析(包括操作分类单元、α多样性、β多样性及物种组成分析)。根据院内预后将脓毒症患者分为生存组(n=40)与死亡组(n=10),比较两组间菌属占比的差异,并采用受试者操作特征(ROC)曲线分析菌属占比与预后的关联。结果 α多样性分析显示,脓毒症组Shannon、Simpson多样性指数均显著低于健康组(均P<0.05)。β多样性分析表明两组菌群结构存在差异。物种组成上,脓毒症组厚壁菌门相对丰度低于健康组,而变形菌门丰度升高。在属水平,脓毒症组肠球菌属、拟杆菌属、乳杆菌属为主要菌属。预后分析显示,死亡组肠杆菌属占比高于生存组(P<0.05),其占比与死亡结局关联的ROC曲线下面积为0.744。结论 脓毒症患者肠道菌群发生紊乱,表现为多样性下降、益生菌减少及机会致病菌增多。本研究初步发现肠杆菌属相对丰度与患者死亡结局存在关联,但其作为独立预后标志物的价值仍需在前瞻性大样本研究中控制关键临床混杂因素后进一步验证。

Objective To investigate the structural and diversity characteristics of the gut microbiota in sepsis patients using 16S rRNA gene sequencing technology, and to preliminarily explore their associations with in-hospital prognosis. Methods A prospective study was conducted to collect fecal samples within 2 days of admission from 50 sepsis patients (sepsis group), while fecal samples from 10 healthy volunteers (healthy group) were collected randomly. The V3-V4 region of the fecal bacterial 16S rRNA gene was sequenced, followed by bioinformatics analysis (including operational taxonomic unit, α-diversity, β-diversity, and species composition analyses). Based on in-hospital outcomes, sepsis patients were divided into a survival group (n=40) or a death group (n=10). Bacterial genus proportions between the two groups were compared, and receiver operating characteristic (ROC) curve analysis was used to evaluate the association between the bacterial genus proportions and prognosis. Results The α-diversity analysis showed that the sepsis group had significantly lower Shannon and Simpson diversity indices compared to the healthy group (all P<0.05). The β-diversity analysis indicated structural differences in microbiota between the two groups. In terms of species composition, the relative abundance of Firmicutes was lower in the sepsis group, while that of Proteobacteria was higher. At the genus level, Enterococcus, Bacteroides, and Lactobacillus were the dominant genera in the sepsis group. Prognostic analysis revealed that the death group had a higher proportion of Enterobacter compared to the survival group (P<0.05), and the area under the ROC curve for its association with mortality was 0.744. Conclusions Sepsis patients exhibit gut microbiota dysbiosis, characterized by reduced diversity, decreased beneficial bacteria, and increased opportunistic pathogens. This study preliminarily suggests an association between the relative abundance of Enterobacter and patient mortality. However, its value as an independent prognostic marker requires further validation in large-scale prospective studies with control for key clinical confounding factors.  

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