Baek Moon Seong, Kim Seungil, Kim Won-Young, Kweon Mi-Na, Huh Jin Won
Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Front Microbiol. 2023 Apr 4;14:1140402. doi: 10.3389/fmicb.2023.1140402. eCollection 2023.
Carbapenem-resistant Enterobacteriaceae (CRE) are an emerging concern for global health and are associated with high morbidity and mortality in critically ill patients. Risk factors for CRE acquisition include broad-spectrum antibiotic use and microbiota dysbiosis in critically ill patients. Therefore, we evaluated the alteration of the intestinal microbiota associated with CRE colonization in critically ill patients.
Fecal samples of 41 patients who were diagnosed with septic shock or respiratory failure were collected after their admission to the intensive care unit (ICU). The gut microbiota profile determined using 16S rRNA gene sequencing and quantitative measurement of fecal short-chain fatty acids were evaluated in CRE-positive ( = 9) and CRE negative ( = 32) patients. The analysis of bacterial metabolic abundance to identify an association between CRE acquisition and metabolic pathway was performed.
CRE carriers showed a significantly increased proportion of the phyla Proteobacteria and decreased numbers of the phyla Bacteroidetes as compared to the CRE non-carriers. Linear discriminant analysis (LDA) with linear discriminant effect size showed that the genera , , , , , , and had an upper 2 LDA score in CRE carriers. The alpha-diversity indices were significantly decreased in CRE carriers, and beta-diversity analysis demonstrated that the two groups were clustered significantly apart. Among short-chain fatty acids, the levels of isobutyric acid and valeric acid were significantly decreased in CRE carriers. Furthermore, the PICRUSt-predicted metabolic pathways revealed significant differences in five features, including ATP-binding cassette transporters, phosphotransferase systems, sphingolipid metabolism, other glycan degradation, and microbial metabolism, in diverse environments between the two groups.
Critically ill patients with CRE have a distinctive gut microbiota composition and community structure, altered short-chain fatty acid production and changes in the metabolic pathways. Further studies are needed to determine whether amino acids supplementation improves microbiota dysbiosis in patients with CRE.
耐碳青霉烯类肠杆菌科细菌（CRE）是全球卫生领域新出现的一个问题，与重症患者的高发病率和高死亡率相关。获得CRE的风险因素包括重症患者使用广谱抗生素和微生物群失调。因此，我们评估了重症患者中与CRE定植相关的肠道微生物群的改变。
对41例诊断为感染性休克或呼吸衰竭的患者在入住重症监护病房（ICU）后采集粪便样本。在CRE阳性（n = 9）和CRE阴性（n = 32）患者中，评估了使用16S rRNA基因测序确定的肠道微生物群谱以及粪便短链脂肪酸的定量测量。进行细菌代谢丰度分析以确定CRE获得与代谢途径之间的关联。
与非CRE携带者相比，CRE携带者中变形菌门的比例显著增加，拟杆菌门的数量减少。具有线性判别效应大小的线性判别分析（LDA）表明，在CRE携带者中，[具体菌属]的LDA得分高于2。CRE携带者的α多样性指数显著降低，β多样性分析表明两组明显聚类分开。在短链脂肪酸中，CRE携带者中异丁酸和戊酸的水平显著降低。此外，PICRUSt预测的代谢途径显示，两组在不同环境中的五个特征存在显著差异，包括ATP结合盒转运蛋白、磷酸转移酶系统、鞘脂代谢、其他聚糖降解和微生物代谢。
患有CRE的重症患者具有独特的肠道微生物群组成和群落结构，短链脂肪酸产生改变以及代谢途径变化。需要进一步研究以确定补充氨基酸是否能改善CRE患者的微生物群失调。
