Alterations in the Gut Microbiome in Liver Recipients with Post-Transplant Diabetes Mellitus
Qi Ling,
Yuqiu Han,
Yue Ma,
Xiaosen Wang,
Zheng Zhu,
Jingyu Wang,
Jiaying Cao,
Xiaohan Lin,
Jun Wang,
Baohong Wang
Affiliations
Qi Ling
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China; Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
Yuqiu Han
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
Yue Ma
CAS Key Laboratory for Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100101, China
Xiaosen Wang
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
Zheng Zhu
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China
Jingyu Wang
Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China; Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China
Jiaying Cao
Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
Xiaohan Lin
Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou 310003, China
Jun Wang
CAS Key Laboratory for Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100101, China; Corresponding authors.
Baohong Wang
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China; Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou 310003, China; Corresponding authors.
Post-transplant diabetes mellitus (PTDM) increases the risk of graft failure and death in liver transplant (LT) recipients. Experimental studies have indicated that enteric dysbiosis mediated by immunosuppressive tacrolimus (TAC) could contribute to glucose disorders, but no data on human recipients with PTDM have been reported. Here, by combining high-throughput shotgun metagenomics sequencing and metabolomics profiling, we characterized the intestinal microbiome (IM) in LT recipient cohort with or without PTDM and deciphered the potential relationship among IM, TAC dosage, and diabetes. By comparing with both non-PTDM and classical type 2 diabetes mellitus (T2DM), we identified microbial signatures of PTDM, which was characterized by the enriched Proteobacteria and decreased Bacteroidetes. Additionally, the altered microbes, as well as the microbial metabolomics, correlated with the dosage of TAC. Specifically, the levels of beneficial microbes associated with PTDM were lowered in recipients with the high TAC trough concentrations (> 5 ng∙mL–1) than those with low ones (< 5 ng∙mL–1), which was accompanied by reduced faecal metabolites involved in the biosynthesis of α-linolenic acid and arachidonic acid-lowering factors of developing T2DM. Moreover, these microbial signatures linked with the extent of glucose disorders in LT recipients. In summary, the faecal microbiome and metabolome differed between PTDM and non-PTDM patients, which were linked with TAC dosage. This study was the first to explore taxonomic alterations and bacterial gene functions to better understand the contribution of the IM to PTDM.
