Gaochen Lu
Zhe Zhao
Yafei Liu
Quan Shen
Pan Li
Yaoyao Chen
Haoran Yin
Huiquan Wang
Cicilia Marcella
Bota Cui
Lei Cheng
Guozhong Ji
Faming Zhang
1 Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China;
2 Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing 210011, China;
3 Tianjin Key Laboratory of Optoelectronic Detection Technology and Systems, Tianjin 300387, China;
4 Department of Microbiology, School of Medicine, Jiangsu University, Zhenjiang 212013, China;
5 Biogas Institute of Ministry of Agriculture and Rural Affairs, Chengdu 610041, China;
6 Center for Anaerobic Microbial Resources of Sichuan Province, Chengdu 610041, China;
7 Division of Microbiotherapy, Sir Run Run Shaw Hospital, Nanjing Medical University, Nanjing 211166, China
Funds: Primary Research & Development Plan of Jiangsu Province (BE2018751)
This work was supported by publicly donated Intestine Initiative Foundation
Jiangsu Provincial Medical Innovation Team (Zhang F), National Natural Science Foundation of China (81600417, 81670495 and 81873548), and China National Center for Clinical Research of Digestive Diseases (201502026).
Received Date: 2019-11-08
Rev Recd Date:2019-12-03
Abstract
Abstract
Fecal microbiota transplantation (FMT) by manual preparation has been applied to treat diseases for thousands of years. However, this method still endures safety risks and challenges the psychological endurance and acceptance of doctors, patients and donors. Population evidence showed the washed microbiota preparation with microfiltration based on an automatic purification system followed by repeated centrifugation plus suspension for three times significantly reduced FMT-related adverse events. This washing preparation makes delivering a precise dose of the enriched microbiota feasible, instead of using the weight of stool. Intraperitoneal injection in mice with the fecal microbiota supernatant obtained after repeated centrifugation plus suspension for three times induced less toxic reaction than that by the first centrifugation following the microfiltration. The toxic reactions that include death, the change in the level of peripheral white blood cells, and the proliferation of germinal center in secondary lymphoid follicles in spleen were noted. The metagenomic next-generation sequencing (NGS) indicated the increasing types and amount of viruses could be washed out during the washing process. Metabolomics analysis indicated metabolites with pro-inflammatory effects in the fecal microbiota supernatant such as leukotriene B4, corticosterone, and prostaglandin G2 could be removed by repeated washing. Near-infrared absorption spectroscopy could be served as a rapid detection method to control the quality of the washingprocess. In conclusion, this study for the first time provides evidence linking clinical findings and animal experiments to support that washed microbiota transplantation (WMT) is safer, more precise and more quality-controllable than the crude FMT by manual.Keywords: fecal microbiota transplantation,
washed microbiota transplantation,
adverse event,
safety,
infection,
virus,
metabolomics,
spectroscopy,
transplant
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