Toshihiko Okumura1, Kazuhiro Horiba1,2,3, Hideya Kamei4, Suguru Takeuchi1, Takako Suzuki1, Yuka Torii1, Jun-Ichi Kawada1, Yoshiyuki Takahashi1, Yasuhiro Ogura4, Tomoo Ogi2,3, Yoshinori Ito5. 1. Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. 2. Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. 3. Department of Human Genetics and Molecular Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan. 4. Department of Transplantation Surgery, Nagoya University Hospital, Nagoya, Japan. 5. Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. yoshi-i@med.nagoya-u.ac.jp.
Abstract
BACKGROUND: Immunosuppression during liver transplantation (LT) enables the prevention and treatment of organ rejection but poses a risk for severe infectious diseases. Immune modulation and antimicrobials affect the plasma microbiome. Thus, determining the impact of immunosuppression on the microbiome may be important to understand immunocompetence, elucidate the source of infection, and predict the risk of infection in LT recipients. We characterized the plasma microbiome of LT recipients at early post-LT and assessed the association between the microbiome and clinical events. RESULTS: In this study, 51 patients who received LT at Nagoya University Hospital from 2016 to 2018 were enrolled. Plasma samples were retrospectively collected at the following time points: 1) within a week after LT; 2) 4 ± 1 weeks after LT; 3) 8 ± 1 weeks after LT; and 4) within 2 days after a positive blood culture. A total of 111 plasma samples were analyzed using shotgun next-generation sequencing (NGS) with the PATHDET pipeline. Relative abundance of Anelloviridae, Nocardiaceae, Microbacteriaceae, and Enterobacteriaceae significantly changed during the postoperative period. Microbiome diversity was higher within a week after LT than that at 8 weeks after LT. Antimicrobials were significantly associated with the microbiome of LT recipients. In addition, the proportion of Enterobacteriaceae was significantly increased and the plasma microbiome diversity was significantly lower in patients with acute cellular rejection (ACR) than non-ACR patients. Sequencing reads of bacteria isolated from blood cultures were predominantly identified by NGS in 8 of 16 samples, and human herpesvirus 6 was detected as a causative pathogen in one recipient with severe clinical condition. CONCLUSIONS: The metagenomic NGS technique has great potential in revealing the plasma microbiome and is useful as a comprehensive diagnostic procedure in clinical settings. Temporal dynamics of specific microorganisms may be used as indirect markers for the determination of immunocompetence and ACR in LT recipients.
BACKGROUND: Immunosuppression during liver transplantation (LT) enables the prevention and treatment of organ rejection but poses a risk for severe infectious diseases. Immune modulation and antimicrobials affect the plasma microbiome. Thus, determining the impact of immunosuppression on the microbiome may be important to understand immunocompetence, elucidate the source of infection, and predict the risk of infection in LT recipients. We characterized the plasma microbiome of LT recipients at early post-LT and assessed the association between the microbiome and clinical events. RESULTS: In this study, 51 patients who received LT at Nagoya University Hospital from 2016 to 2018 were enrolled. Plasma samples were retrospectively collected at the following time points: 1) within a week after LT; 2) 4 ± 1 weeks after LT; 3) 8 ± 1 weeks after LT; and 4) within 2 days after a positive blood culture. A total of 111 plasma samples were analyzed using shotgun next-generation sequencing (NGS) with the PATHDET pipeline. Relative abundance of Anelloviridae, Nocardiaceae, Microbacteriaceae, and Enterobacteriaceae significantly changed during the postoperative period. Microbiome diversity was higher within a week after LT than that at 8 weeks after LT. Antimicrobials were significantly associated with the microbiome of LT recipients. In addition, the proportion of Enterobacteriaceae was significantly increased and the plasma microbiome diversity was significantly lower in patients with acute cellular rejection (ACR) than non-ACRpatients. Sequencing reads of bacteria isolated from blood cultures were predominantly identified by NGS in 8 of 16 samples, and human herpesvirus 6 was detected as a causative pathogen in one recipient with severe clinical condition. CONCLUSIONS: The metagenomic NGS technique has great potential in revealing the plasma microbiome and is useful as a comprehensive diagnostic procedure in clinical settings. Temporal dynamics of specific microorganisms may be used as indirect markers for the determination of immunocompetence and ACR in LT recipients.
Authors: Nan Qin; Fengling Yang; Ang Li; Edi Prifti; Yanfei Chen; Li Shao; Jing Guo; Emmanuelle Le Chatelier; Jian Yao; Lingjiao Wu; Jiawei Zhou; Shujun Ni; Lin Liu; Nicolas Pons; Jean Michel Batto; Sean P Kennedy; Pierre Leonard; Chunhui Yuan; Wenchao Ding; Yuanting Chen; Xinjun Hu; Beiwen Zheng; Guirong Qian; Wei Xu; S Dusko Ehrlich; Shusen Zheng; Lanjuan Li Journal: Nature Date: 2014-07-23 Impact factor: 49.962
Authors: Zeneng Wang; Elizabeth Klipfell; Brian J Bennett; Robert Koeth; Bruce S Levison; Brandon Dugar; Ariel E Feldstein; Earl B Britt; Xiaoming Fu; Yoon-Mi Chung; Yuping Wu; Phil Schauer; Jonathan D Smith; Hooman Allayee; W H Wilson Tang; Joseph A DiDonato; Aldons J Lusis; Stanley L Hazen Journal: Nature Date: 2011-04-07 Impact factor: 49.962
Authors: Hila Mizrahi; Avi Peretz; René Lesnik; Yana Aizenberg-Gershtein; Sara Rodríguez-Martínez; Yehonatan Sharaby; Nina Pastukh; Ingrid Brettar; Manfred G Höfle; Malka Halpern Journal: Sci Rep Date: 2017-01-06 Impact factor: 4.379
Authors: Iwijn De Vlaminck; Kiran K Khush; Calvin Strehl; Bitika Kohli; Helen Luikart; Norma F Neff; Jennifer Okamoto; Thomas M Snyder; David N Cornfield; Mark R Nicolls; David Weill; Daniel Bernstein; Hannah A Valantine; Stephen R Quake Journal: Cell Date: 2013-11-21 Impact factor: 41.582
Authors: K G Joensen; A L Ø Engsbro; O Lukjancenko; R S Kaas; O Lund; H Westh; F M Aarestrup Journal: Eur J Clin Microbiol Infect Dis Date: 2017-03-11 Impact factor: 3.267