Alterations in gut microbiome and metabolomics in chronic hepatitis B infection-associated liver disease and their impact on peripheral immune response
Yue Shen,
Sheng-Di Wu,
Yao Chen,
Xin-Yue Li,
Qin Zhu,
Kiyoko Nakayama,
Wan-Qin Zhang,
Cheng-Zhao Weng,
Jun Zhang,
Hai-Kun Wang,
Jian Wu,
Wei Jiang
Affiliations
Yue Shen
Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, China
Sheng-Di Wu
Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, China
Yao Chen
Department of Emergency Medicine, Zhongshan Hospital of Fudan University, Shanghai, China
Xin-Yue Li
Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai, China
Qin Zhu
Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, China
Kiyoko Nakayama
Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, China
Wan-Qin Zhang
Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, China
Cheng-Zhao Weng
Department of Gastroenterology& Hepatology, Zhongshan Hospital Xiamen Branch of Fudan University, Xiamen, China
Jun Zhang
Department of Gastroenterology& Hepatology, Zhongshan Hospital Xiamen Branch of Fudan University, Xiamen, China
Hai-Kun Wang
CAS Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
Jian Wu
Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, China
Wei Jiang
Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, China
ABSTRACTGut dysbiosis has been reported in chronic hepatitis B (CHB) infection, however its role in CHB progression and antiviral treatment remains to be clarified. Herein, the present study aimed to characterize gut microbiota (GM) in patients with chronic hepatitis B virus infection-associated liver diseases (HBV-CLD) by combining microbiome with metabolome analyses and to evaluate their effects on peripheral immunity. Fecal samples from HBV-CLD patients (n = 64) and healthy controls (n = 17) were collected for 16s rRNA sequencing. Fecal metabolomics was measured with untargeted liquid chromatography-mass spectrometry in subgroups of 58 subjects. Lineage changes of peripheral blood mononuclear cells (PBMCs) were determined upon exposure to bacterial extracts (BE) from HBV-CLD patients. Integrated analyses of microbiome with metabolome revealed a remarkable shift of gut microbiota and metabolites in HBV-CLD patients, and disease progression and antiviral treatment were found to be two main contributing factors for the shift. Concordant decreases in Turicibacter with 4-hydroxyretinoic acid were detected to be inversely correlated with serum AST levels through host-microbiota-metabolite interaction analysis in cirrhotic patients. Moreover, depletion of E.hallii group with elevated choline was restored in patients with 5-year antiviral treatment. PBMC exposure to BE from non-cirrhotic patients enhanced expansion of T helper 17 cells; however, BE from cirrhotics attenuated T helper 1 cell count. CHB progression and antiviral treatment are two main factors contributing to the compositional shift in microbiome and metabolome of HBV-CLD patients. Peripheral immunity might be an intermediate link in gut microbe-host interplay underlying CHB pathogenesis.
