Prolonged Impairment of Short-Chain Fatty Acid and L-Isoleucine Biosynthesis in Gut Microbiome in Patients With COVID-19.
Prolonged Impairment of Short-Chain Fatty Acid and L-Isoleucine Biosynthesis in Gut Microbiome in Patients With COVID-19.
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DOI：
10.1053/j.gastro.2021.10.013
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发表时间：
2022-03
期刊：
影响因子：
29.4
通讯作者：
Ng SC
中科院分区：
文献类型：
--
作者：
Zhang F;Wan Y;Zuo T;Yeoh YK;Liu Q;Zhang L;Zhan H;Lu W;Xu W;Lui GCY;Li AYL;Cheung CP;Wong CK;Chan PKS;Chan FKL;Ng SC
由严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）感染引起的2019年冠状病毒病（COVID-19）与肠道微生物群组成的改变有关。参与短链脂肪酸（SCFAs）代谢的肠道细菌的系统发育组在SARS-CoV-2感染患者中被耗尽。我们的目的是描述COVID-19患者在疾病消退前后肠道微生物组的功能特征。我们对来自66名未经治疗的COVID-19患者和70名非COVID-19对照的粪便样本进行了鸟枪宏基因组测序。在住院期间和出院后1个月以上收集连续粪便样本（最多6个时间点）。我们评估了肠道微生物途径与疾病严重程度和血液炎症标志物的关系。我们还确定了疾病消退前后粪便样本中微生物功能的变化，并使用粪便代谢物的靶向分析来验证这些功能。与非COVID-19对照组相比，COVID-19重症/危重症患者的肠道微生物组功能出现显著改变（P < .001），其特征是肠道微生物组SCFA和L-异亮氨酸生物合成能力受损，尿素生成能力增强。COVID-19患者恢复后，肠道微生物组中SCFA和L-异亮氨酸生物合成受损持续超过30天。粪便代谢物的靶向分析显示，COVID-19患者在疾病消退前后的SCFA和L-异亮氨酸粪便浓度显著降低。SCFA和L-异亮氨酸生物合成的缺乏与疾病严重程度和CXCL-10、NT-前B型利钠肽和C-反应蛋白的血浆浓度增加显著相关（均P <0.05）。COVID-19患者的肠道微生物组显示出SCFA和L-异亮氨酸生物合成能力受损，即使在疾病消退后也持续存在。这两种微生物功能与宿主免疫应答相关，强调了肠道微生物功能在SARS-CoV-2感染发病机制和结果中的重要性。2019年冠状病毒病患者的肠道微生物组显示短链脂肪酸和L-异亮氨酸生物合成能力受损。需要进一步研究以了解受损的肠道微生物功能如何参与疾病结果。
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with altered gut microbiota composition. Phylogenetic groups of gut bacteria involved in the metabolism of short chain fatty acids (SCFAs) were depleted in SARS-CoV-2–infected patients. We aimed to characterize a functional profile of the gut microbiome in patients with COVID-19 before and after disease resolution. We performed shotgun metagenomic sequencing on fecal samples from 66 antibiotics-naïve patients with COVID-19 and 70 non–COVID-19 controls. Serial fecal samples were collected (at up to 6 times points) during hospitalization and beyond 1 month after discharge. We assessed gut microbial pathways in association with disease severity and blood inflammatory markers. We also determined changes of microbial functions in fecal samples before and after disease resolution and validated these functions using targeted analysis of fecal metabolites. Compared with non–COVID-19 controls, patients with COVID-19 with severe/critical illness showed significant alterations in gut microbiome functionality (P < .001), characterized by impaired capacity of gut microbiome for SCFA and L-isoleucine biosynthesis and enhanced capacity for urea production. Impaired SCFA and L-isoleucine biosynthesis in gut microbiome persisted beyond 30 days after recovery in patients with COVID-19. Targeted analysis of fecal metabolites showed significantly lower fecal concentrations of SCFAs and L-isoleucine in patients with COVID-19 before and after disease resolution. Lack of SCFA and L-isoleucine biosynthesis significantly correlated with disease severity and increased plasma concentrations of CXCL-10, NT- proB-type natriuretic peptide, and C-reactive protein (all P < .05). Gut microbiome of patients with COVID-19 displayed impaired capacity for SCFA and L-isoleucine biosynthesis that persisted even after disease resolution. These 2 microbial functions correlated with host immune response underscoring the importance of gut microbial functions in SARS-CoV-2 infection pathogenesis and outcome. Gut microbiome of patients with coronavirus disease 2019 displayed impaired capacity for short chain fatty acids and L-isoleucine biosynthesis. Further studies are needed to understand how impaired gut microbial functions are involved in disease outcome.
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影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
DOI：
10.1073/pnas.1019378108
发表时间：
2011-03-29
影响因子：
11.1
作者：
Ichinohe, Takeshi;Pang, Iris K.;Iwasaki, Akiko
通讯作者：
Iwasaki, Akiko
影响因子：
5
作者：
Lippi, Giuseppe;Plebani, Mario;Henry, Brandon Michael
通讯作者：
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影响因子：
5.8
作者：
Gao, Lei;Jiang, Dan;Zhang, Dong-ying
通讯作者：
Zhang, Dong-ying
DOI：
10.1126/science.aam5336
发表时间：
2017-08-04
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Steed AL;Christophi GP;Kaiko GE;Sun L;Goodwin VM;Jain U;Esaulova E;Artyomov MN;Morales DJ;Holtzman MJ;Boon ACM;Lenschow DJ;Stappenbeck TS
通讯作者：
Stappenbeck TS