Preclinical safety,effectiveness evaluation,and screening of functional bacteria for fecal microbiota transplantation based on germ-free animals

Fecal microbiota transplantation(FMT),also known as fecal bacterial therapy,is a treatment option that can quickly reconstruct the normal composition of intestinal microbes,and it has a good therapeutic effect on Clostridium difficile infection,as well as on other microecological disorders.However,the causal mechanism of FMT efficacy remains to be clarified,its safety is a major problem,and the standardization and acceptability of FMT need to be improved.This review summarizes its current research status and potential research areas that need to be strengthened,and proposes to clarify the safety of FMT and the causal relationship between FMT and therapeutic effectiveness based on germ-free animals.Meanwhile,the research system is combined with multiomics technology to screen the effective bacteria in FMT,and develop standard,safe,effective and controllable flora of FMT.

Washed microbiota transplantation vs.manual fecal microbiota transplantation:clinical findings,animal studies and in vitro screening

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.

Microbiota transplantation： concept, methodology and strategy for its modernization

Fecal microbiota transplantation （FMT） has become a research focus of biomedicine and clinical medicine in recent years. The clinical response from FMT for different diseases provided evidence for microbiota-host interactions associated with various disorders, including Clostridium difficile infection, inflammatory bowel disease, diabetes mellitus, cancer, liver cirrhosis, gut- brain disease and others. To discuss the experiences of using microbes to treat human diseases from ancient China to current era should be important in moving standardized FMT forward and achieving a better future. Here, we review the changing concept of microbiota transplantation from FMT to selective microbiota transplantation, methodology development of FMT and step- up FMT strategy based on literature and state experts＇ perspectives.

Seven facts and five initiatives for gut microbiome research

The gut microbiome has attracted increasing attention over the past 15 years.Along with the fast-growing body of research literature and media reports,the public's opinions on the gut microbiome have begun to appear polarized.Some believe that the gut microbiome is at the core of human health and is related to every single disease.To the opposite,some people question the scientific basis of gut microbiome studies and criticize that many of them are farfetched;there is even a joke spreading in the biomedical research field—"keeping gut microbiome in mind,no mechanism is hard to find".