Gegen Qinlian Decoction(GQD),a traditional Chinese medicine(TCM)formula,has long been used for the treatment of common metabolic diseases,including type 2 diabetes mellitus.However,the main limitation of its wider app...Gegen Qinlian Decoction(GQD),a traditional Chinese medicine(TCM)formula,has long been used for the treatment of common metabolic diseases,including type 2 diabetes mellitus.However,the main limitation of its wider application is ingredient complexity of this formula.Thus,it is critically important to identify the major active ingredients of GQD and to illustrate mechanisms underlying its action.Here,we compared the effects of GQD and berberine,a hypothetical key active pharmaceutical ingredient of GQD,on a diabetic rat model by comprehensive analyses of gut microbiota,short-chain fatty acids,proinflammatory cytokines,and ileum transcriptomics.Our results show that berberine and GQD had similar effects on lowering blood glucose levels,modulating gut microbiota,inducing ileal gene expression,as well as relieving systemic and local inflammation.As expected,both berberine and GQD treatment significantly altered the overall gut microbiota structure and enriched many butyrate-producing bacteria,including Faecalibacterium and Roseburia,thereby attenuating intestinal inflammation and lowering glucose.Levels of short-chain fatty acids in rat feces were also significantly elevated after treatment with berberine or GQD.Moreover,concentration of serum proinflammatory cytokines and expression of immune-related genes,including Nfkb1,Stat1,and Ifnrg1,in pancreatic islets were significantly reduced after treatment.Our study demonstrates that the main effects of GQD can be attributed to berberine via modulating gut microbiota.The strategy employed would facilitate further standardization and widespread application of TCM in many diseases.展开更多
The emergence and spread of plasmid-mediated tigecycline resistance genes have attracted extensive attention worldwide.We investigated the distribution of mobile tigecycline resistance genes in Salmonella genomes gene...The emergence and spread of plasmid-mediated tigecycline resistance genes have attracted extensive attention worldwide.We investigated the distribution of mobile tigecycline resistance genes in Salmonella genomes generated by both our laboratory and public bacterial genomes downloaded from the NCBI GenBank.The tet(X4)-positive strains were subjected to susceptibility testing and conjugation assays.The genetic features of the tet(X4)-bearing plasmid sequence were analyzed.Here,we report the identification of the plasmid-mediated tigecycline resistance gene tet(X4)in a conjugative plasmid of the Salmonella enterica serovar Llandoff strain SH16G3606,isolated from a man in China in 2016,the first reported serovar Llandoff in China as a novel sequence type ST8300.The tet(X4)-mediated resistance phenotype was successfully transferred from the Salmonella Llandoff strain into Escherichia coli J53,resulting in a 32-fold increase in the minimal inhibitory concentration of tigecycline.The tet(X4)gene was located between two copies of ISCR2 in the plasmid pSal21GXH-tetX4.To our knowledge,this is the first report of the plasmid-mediated tigecycline resistance gene tet(X4)in a Salmonella Llandoff strain isolated from a human stool sample in China.In addition,our findings demonstrated that a total of 171 isolates are carrying tet(X)-like genes distributed in 21 countries or areas across 6 continents,posing a serious threat to humans and public health.Overall,our timely discovery of the recent emergence of the tet(X4)gene in Salmonella isolates and other Enterobacteriaceae bacteria species supports the need for rapid surveillance to prevent the tet(X)-like gene from spreading.展开更多
基金This work was supported by the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB29020000)the National Key R&D Program of China(Grant No.2018YFC2000500)the National Natural Science Foundation of China(Grant Nos.81704067,81430097,and 31771481).
文摘Gegen Qinlian Decoction(GQD),a traditional Chinese medicine(TCM)formula,has long been used for the treatment of common metabolic diseases,including type 2 diabetes mellitus.However,the main limitation of its wider application is ingredient complexity of this formula.Thus,it is critically important to identify the major active ingredients of GQD and to illustrate mechanisms underlying its action.Here,we compared the effects of GQD and berberine,a hypothetical key active pharmaceutical ingredient of GQD,on a diabetic rat model by comprehensive analyses of gut microbiota,short-chain fatty acids,proinflammatory cytokines,and ileum transcriptomics.Our results show that berberine and GQD had similar effects on lowering blood glucose levels,modulating gut microbiota,inducing ileal gene expression,as well as relieving systemic and local inflammation.As expected,both berberine and GQD treatment significantly altered the overall gut microbiota structure and enriched many butyrate-producing bacteria,including Faecalibacterium and Roseburia,thereby attenuating intestinal inflammation and lowering glucose.Levels of short-chain fatty acids in rat feces were also significantly elevated after treatment with berberine or GQD.Moreover,concentration of serum proinflammatory cytokines and expression of immune-related genes,including Nfkb1,Stat1,and Ifnrg1,in pancreatic islets were significantly reduced after treatment.Our study demonstrates that the main effects of GQD can be attributed to berberine via modulating gut microbiota.The strategy employed would facilitate further standardization and widespread application of TCM in many diseases.
基金This study was supported by the Major Program of National Natural Science Foundation of China(81991534)the Major State Basic Research Development Program(2018YFC1603803)the National Key Research and Development Program of China(grant number:2018YFC1603900).
文摘The emergence and spread of plasmid-mediated tigecycline resistance genes have attracted extensive attention worldwide.We investigated the distribution of mobile tigecycline resistance genes in Salmonella genomes generated by both our laboratory and public bacterial genomes downloaded from the NCBI GenBank.The tet(X4)-positive strains were subjected to susceptibility testing and conjugation assays.The genetic features of the tet(X4)-bearing plasmid sequence were analyzed.Here,we report the identification of the plasmid-mediated tigecycline resistance gene tet(X4)in a conjugative plasmid of the Salmonella enterica serovar Llandoff strain SH16G3606,isolated from a man in China in 2016,the first reported serovar Llandoff in China as a novel sequence type ST8300.The tet(X4)-mediated resistance phenotype was successfully transferred from the Salmonella Llandoff strain into Escherichia coli J53,resulting in a 32-fold increase in the minimal inhibitory concentration of tigecycline.The tet(X4)gene was located between two copies of ISCR2 in the plasmid pSal21GXH-tetX4.To our knowledge,this is the first report of the plasmid-mediated tigecycline resistance gene tet(X4)in a Salmonella Llandoff strain isolated from a human stool sample in China.In addition,our findings demonstrated that a total of 171 isolates are carrying tet(X)-like genes distributed in 21 countries or areas across 6 continents,posing a serious threat to humans and public health.Overall,our timely discovery of the recent emergence of the tet(X4)gene in Salmonella isolates and other Enterobacteriaceae bacteria species supports the need for rapid surveillance to prevent the tet(X)-like gene from spreading.
