Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients
Zhonghan Sun,
Zhi-Gang Song,
Chenglin Liu,
Shishang Tan,
Shuchun Lin,
Jiajun Zhu,
Fa-Hui Dai,
Jian Gao,
Jia-Lei She,
Zhendong Mei,
Tao Lou,
Jiao-Jiao Zheng,
Yi Liu,
Jiang He,
Yuanting Zheng,
Chen Ding,
Feng Qian,
Yan Zheng,
Yan-Mei Chen
Affiliations
Zhonghan Sun
State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Zhi-Gang Song
Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Chenglin Liu
State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Shishang Tan
State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Shuchun Lin
State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Jiajun Zhu
State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Fa-Hui Dai
Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Jian Gao
State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Jia-Lei She
Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Zhendong Mei
State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Tao Lou
State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Jiao-Jiao Zheng
Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Yi Liu
Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Jiang He
State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Yuanting Zheng
State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Chen Ding
State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Feng Qian
State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Yan Zheng
State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Yan-Mei Chen
Shanghai Public Health Clinical Center, State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University
Abstract Background COVID-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. Methods To 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. Results Altered 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. Conclusions Our 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.
