Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients

BMC Medicine

Fa-Hui Dai¹  Yi Liu¹  Jia-Lei She¹  Jiao-Jiao Zheng¹  Yan-Mei Chen¹  Zhi-Gang Song²  Shishang Tan³  Jian Gao³  Jiang He³  Yuanting Zheng³  Jiajun Zhu³  Shuchun Lin³  Zhendong Mei³  Tao Lou³  Feng Qian³  Chenglin Liu³  Chen Ding³  Zhonghan Sun⁴  Yan Zheng⁵ 

[1] Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China;Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China;Institutes of Biomedical Sciences, Fudan University, Shanghai, China;State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China;State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China;Ministry of Education Key Laboratory of Contemporary Anthropology, Fudan University, Shanghai, China;State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai, China;Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, China;

关键词: COVID-19;    SARS-CoV-2;    Microbiome;    Metaproteomic;    Gut barrier;    Immune homeostasis;   

DOI  :  10.1186/s12916-021-02212-0

来源: Springer

【 摘 要 】

BackgroundCOVID-19 is an infectious disease characterized by multiple respiratory and extrapulmonary manifestations, including gastrointestinal symptoms. Although recent studies have linked gut microbiota to infectious diseases such as influenza, little is known about the role of the gut microbiota in COVID-19 pathophysiology.MethodsTo better understand the host-gut microbiota interactions in COVID-19, we characterized the gut microbial community and gut barrier function using metagenomic and metaproteomic approaches in 63 COVID-19 patients and 8 non-infected controls. Both immunohematological parameters and transcriptional profiles were measured to reflect the immune response in COVID-19 patients.ResultsAltered gut microbial composition was observed in COVID-19 patients, which was characterized by decreased commensal species and increased opportunistic pathogenic species. Severe illness was associated with higher abundance of four microbial species (i.e., Burkholderia contaminans, Bacteroides nordii, Bifidobacterium longum, and Blautia sp. CAG 257), six microbial pathways (e.g., glycolysis and fermentation), and 10 virulence genes. These severity-related microbial features were further associated with host immune response. For example, the abundance of Bu. contaminans was associated with higher levels of inflammation biomarkers and lower levels of immune cells. Furthermore, human-origin proteins identified from both blood and fecal samples suggested gut barrier dysfunction in COVID-19 patients. The circulating levels of lipopolysaccharide-binding protein increased in patients with severe illness and were associated with circulating inflammation biomarkers and immune cells. Besides, proteins of disease-related bacteria (e.g., B. longum) were detectable in blood samples from patients.ConclusionsOur results suggest that the dysbiosis of the gut microbiome and the dysfunction of the gut barrier might play a role in the pathophysiology of COVID-19 by affecting host immune homeostasis.

【 授权许可】

CC BY