Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut mi...Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbehost interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include(1) the mode of delivery(vaginal or caesarean);(2) diet during infancy(breast milk or formula feeds) and adulthood(vegan based or meat based); and(3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.展开更多
AIM To study the influence of different doses of tacrolimus(FK506)on gut microbiota after liver transplantation(LT)in rats.METHODS Specific pathogen-free Brown Norway(BN)rats and Lewis rats were separated into five gr...AIM To study the influence of different doses of tacrolimus(FK506)on gut microbiota after liver transplantation(LT)in rats.METHODS Specific pathogen-free Brown Norway(BN)rats and Lewis rats were separated into five groups:(1)Tolerance group(BN-BN LT,n=8);(2)rejection group(Lewis-BN LT,n=8);(3)high dosage FK506(FK506-H)group(Lewis-BN LT,n=8);(4)middle dosage FK506(FK506-M)group(Lewis-BN LT,n=8);and(5)low dosage FK506(FK506-L)group(LewisBN LT,n=8).FK506 was administered to recipients at a dose of 1.0 mg/kg,0.5 mg/kg,and 0.1 mg/kg body weight for 29 d after LT to the FK506-H,FK506-M,and FK506-L groups,respectively.On the 30^(th) day after LT,all rats were sampled and euthanized.Blood samples were harvested for liver function and plasma endotoxin testing.Hepatic graft and ileocecal tissues were collected for histopathology observation.Ileocecal contents were used for DNA extraction,Real-time quantitative polymerase chain reaction(RT-PCR)and digital processing of denaturing gradient gel electrophoresis(DGGE)profiles and analysis.RESULTS Compared to the FK506-H and FK506-L groups,FK506-M was optimal for maintaining immunosuppression and inducing normal graft function;the FK506-M maintained gut barrier integrity and low plasma endotoxin levels;furthermore,DGGE results showed that FK506-M induced stable gut microbiota.Diversity analysis indicated that FK506-M increased species richness and rare species abundance,and cluster analysis confirmed the stable gut microbiota induced by FK506-M.Phylogenetic tree analysis identified crucial bacteria associated with FK506-M;seven of the nine bacteria that were decreased corresponded to Bacteroidetes,while increased bacteria were of the Bifidobacterium species.FK506-M increased Faecalibacterium prausnitzii and Bifidobacterium spp.and decreased Bacteroides-Prevotella and Enterobacteriaceae,as assessed by RT-PCR,which confirmed the crucial bacterial alterations identified through DGGE.CONCLUSION Compared to the low or high dosage of FK506,an optimal dosage of FK506 induced immunosuppression,normal graft function and stable gut microbiota following LT in rats.The stable gut microbiota presented increased probiotics and decreased potential pathogenic endotoxin-producing bacteria.These findings provide a novel strategy based on gut microbiota for immunosuppressive dosage assessment for recipients following LT.展开更多
A 58-year-old patient diagnosed with fibromyalgia, irritable bowel syndrome (IBS) and chronic fatigue syndrome (CFS), non-responsive to variety of treatments over the years, suffered from significant social and occupa...A 58-year-old patient diagnosed with fibromyalgia, irritable bowel syndrome (IBS) and chronic fatigue syndrome (CFS), non-responsive to variety of treatments over the years, suffered from significant social and occupational disabilities. The patient was interested in fecal microbiota transplantation (FMT), but given that FMT is not approved for these indications, he used an online protocol for FMT screening and preparation and self-instilled the filtrate using an enema 6 times. FMT resulted in a gradual improvement of symptoms and 9 months after the last treatment, the patient reported full recovery of symptoms, going back to work at full time employment. Improvement of symptoms was associated with major alterations of the enteric microbiota, according to next generation sequencing analysis performed before the first FMT and after the last FMT. Most prominent alterations at the genus level included a decrease in fecal Streptococcus proportion from 26.39% to 0.15% and an increase in Bifidobacterium from 0% to 5.23%. This case is added to several additional case reports that demonstrated the effectivity of FMT in these functional disorders that are lacking an otherwise good medical therapeutic intervention. We conclude that randomized controlled trials are required to ground FMT as a possible therapy for these difficult-to-treat conditions.展开更多
文摘Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbehost interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include(1) the mode of delivery(vaginal or caesarean);(2) diet during infancy(breast milk or formula feeds) and adulthood(vegan based or meat based); and(3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.
基金Supported by the National Natural Science Foundation of China,No.81672422,No.81600506,and No.81702757Open Project in State Key Laboratory for Diagnosis and Treatment of Infectious Disease,No.2015KF03+4 种基金National S&T Major Project of China,No.2018ZX10301201Natural Science Foundation of Zhejiang Province,No.LY15H160033China Postdoctoral Science Foundation,No.2017464Zhejiang Province Health Department Program,No.2014KYB081,and No.2017KY322Academician Jieshou Li Mucosal Barrier Fund,No.201208
文摘AIM To study the influence of different doses of tacrolimus(FK506)on gut microbiota after liver transplantation(LT)in rats.METHODS Specific pathogen-free Brown Norway(BN)rats and Lewis rats were separated into five groups:(1)Tolerance group(BN-BN LT,n=8);(2)rejection group(Lewis-BN LT,n=8);(3)high dosage FK506(FK506-H)group(Lewis-BN LT,n=8);(4)middle dosage FK506(FK506-M)group(Lewis-BN LT,n=8);and(5)low dosage FK506(FK506-L)group(LewisBN LT,n=8).FK506 was administered to recipients at a dose of 1.0 mg/kg,0.5 mg/kg,and 0.1 mg/kg body weight for 29 d after LT to the FK506-H,FK506-M,and FK506-L groups,respectively.On the 30^(th) day after LT,all rats were sampled and euthanized.Blood samples were harvested for liver function and plasma endotoxin testing.Hepatic graft and ileocecal tissues were collected for histopathology observation.Ileocecal contents were used for DNA extraction,Real-time quantitative polymerase chain reaction(RT-PCR)and digital processing of denaturing gradient gel electrophoresis(DGGE)profiles and analysis.RESULTS Compared to the FK506-H and FK506-L groups,FK506-M was optimal for maintaining immunosuppression and inducing normal graft function;the FK506-M maintained gut barrier integrity and low plasma endotoxin levels;furthermore,DGGE results showed that FK506-M induced stable gut microbiota.Diversity analysis indicated that FK506-M increased species richness and rare species abundance,and cluster analysis confirmed the stable gut microbiota induced by FK506-M.Phylogenetic tree analysis identified crucial bacteria associated with FK506-M;seven of the nine bacteria that were decreased corresponded to Bacteroidetes,while increased bacteria were of the Bifidobacterium species.FK506-M increased Faecalibacterium prausnitzii and Bifidobacterium spp.and decreased Bacteroides-Prevotella and Enterobacteriaceae,as assessed by RT-PCR,which confirmed the crucial bacterial alterations identified through DGGE.CONCLUSION Compared to the low or high dosage of FK506,an optimal dosage of FK506 induced immunosuppression,normal graft function and stable gut microbiota following LT in rats.The stable gut microbiota presented increased probiotics and decreased potential pathogenic endotoxin-producing bacteria.These findings provide a novel strategy based on gut microbiota for immunosuppressive dosage assessment for recipients following LT.
文摘A 58-year-old patient diagnosed with fibromyalgia, irritable bowel syndrome (IBS) and chronic fatigue syndrome (CFS), non-responsive to variety of treatments over the years, suffered from significant social and occupational disabilities. The patient was interested in fecal microbiota transplantation (FMT), but given that FMT is not approved for these indications, he used an online protocol for FMT screening and preparation and self-instilled the filtrate using an enema 6 times. FMT resulted in a gradual improvement of symptoms and 9 months after the last treatment, the patient reported full recovery of symptoms, going back to work at full time employment. Improvement of symptoms was associated with major alterations of the enteric microbiota, according to next generation sequencing analysis performed before the first FMT and after the last FMT. Most prominent alterations at the genus level included a decrease in fecal Streptococcus proportion from 26.39% to 0.15% and an increase in Bifidobacterium from 0% to 5.23%. This case is added to several additional case reports that demonstrated the effectivity of FMT in these functional disorders that are lacking an otherwise good medical therapeutic intervention. We conclude that randomized controlled trials are required to ground FMT as a possible therapy for these difficult-to-treat conditions.
