Lactobacillus are considered promising therapeutic methods for nonalcoholic fatty liver disease(NAFLD).The effects of two strains of Ltmosilactobacillus mucosae on NAFLD were investigated in this study.Fourweek-old ma...Lactobacillus are considered promising therapeutic methods for nonalcoholic fatty liver disease(NAFLD).The effects of two strains of Ltmosilactobacillus mucosae on NAFLD were investigated in this study.Fourweek-old male C57BL/6J mice were divided into 4 groups(n=8 per group,Control,Model,FZJTZ26M3,FGSYC17L3).L.mucosae FZJTZ26M3 reduced the mice 's body weight,liver weight,and adipose tissue weight after 12 weeks of therapy.According to serum analysis,total cholesterol,triacylglycerol,and low-density lipoprotein cholesterol significantly decreased after L.mucosae FZJTZ26M3 intervention.Liver pathology showed that L.mucosae FZJTZ26M3 was effective to ameliorate lipid deposition in NAFLD mice.Additionally,the expression of the gene related to lipid metabolism in the liver and adipose tissue was analyzed,and the results indicated that L.mucosae FZJTZ26M3 could alleviate NAFLD by regulating lipid metabolism.Furthermore,the results of 16S rRNA gene sequencing revealed a drop in the relative abundance of Ruminococcaceae,which is linked to inflammation,but the relative abundance of a potential probiotic Akkermansia significantly increased after L.mucosae FZJTZ26M3 intervention.Generally,L.mucosae FZJTZ26M3 could be a candidate to prevent NAFLD.展开更多
Crohn’s disease(CD)is an inflammatory bowel disease characterized by immunemediated flares affecting any region of the intestine alternating with remission periods.In CD,the ileum is frequently affected and about one...Crohn’s disease(CD)is an inflammatory bowel disease characterized by immunemediated flares affecting any region of the intestine alternating with remission periods.In CD,the ileum is frequently affected and about one third of patients presents with a pure ileal type.Moreover,the ileal type of CD presents epidemiological specificities like a younger age at onset and often a strong link with smoking and genetic susceptibility genes.Most of these genes are associated with Paneth cell dysfunction,a cell type found in the intestinal crypts of the ileum.Besides,a Western-type diet is associated in epidemiological studies with CD onset and increasing evidence shows that diet can modulate the composition of bile acids and gut microbiota,which in turn modulates the susceptibility of the ileum to inflammation.Thus,the interplay between environmental factors and the histological and anatomical features of the ileum is thought to explain the specific transcriptome profile observed in CD ileitis.Indeed,both immune response and cellular healing processes harbour differences between ileal and non-ileal CD.Taken together,these findings advocate for a dedicated therapeutic approach to managing ileal CD.Currently,interventional pharmacological studies have failed to clearly demonstrate distinct response profiles according to disease site.However,the high rate of stricturing disease in ileal CD requires the identification of new therapeutic targets to significantly change the natural history of this debilitating disease.展开更多
BACKGROUND The Centers for Disease Control and Prevention estimate that Clostridioides difficile(C.difficile)causes half a million infections(CDI)annually and is a major cause of total infectious disease death in the ...BACKGROUND The Centers for Disease Control and Prevention estimate that Clostridioides difficile(C.difficile)causes half a million infections(CDI)annually and is a major cause of total infectious disease death in the United States,causing inflammation of the colon and potentially deadly diarrhea.We recently reported the isolation of ADS024,a Bacillus velezensis(B.velezensis)strain,which demonstrated direct in vitro bactericidal activity against C.difficile,with minimal collateral impact on other members of the gut microbiota.In this study,we hypothesized that in vitro activities of ADS024 will translate in vivo to protect against CDI challenge in mouse models.AIM To investigate the in vivo efficacy of B.velezensis ADS024 in protecting against CDI challenge in mouse models.METHODS To mimic disruption of the gut microbiota,the mice were exposed to vancomycin prior to dosing with ADS024.For the mouse single-dose study,the recovery of ADS024 was assessed via microbiological analysis of intestinal and fecal samples at 4 h,8 h,and 24 h after a single oral dose of 5×108 colony-forming units(CFU)/mouse of freshly grown ADS024.The single-dose study in miniature swine included groups that had been pre-dosed with vancomycin and that had been exposed to a dose range of ADS024,and a group that was not pre-dosed with vancomycin and received a single dose of ADS024.The ADS024 colonies[assessed by quantitative polymerase chain reaction(qPCR)using ADS024-specific primers]were counted on agar plates.For the 28-d miniature swine study,qPCR was used to measure ADS024 levels from fecal samples after oral administration of ADS024 capsules containing 5×109 CFU for 28 consecutive days,followed by MiSeq compositional sequencing and bioinformatic analyses to measure the impact of ADS024 on microbiota.Two studies were performed to determine the efficacy of ADS024 in a mouse model of CDI:Study 1 to determine the effects of fresh ADS024 culture and ADS024 spore preparations on the clinical manifestations of CDI in mice,and Study 2 to compare the efficacy of single daily doses vs dosing 3 times per day with fresh ADS024.C.difficile challenge was performed 24 h after the start of ADS024 exposure.To model the human distal colon,an anerobic fecal fermentation system was used.MiSeq compositional sequencing and bioinformatic analyses were performed to measure microbiota diversity changes following ADS024 treatment.To assess the potential of ADS024 to be a source of antibiotic resistance,its susceptibility to 18 different antibiotics was tested.RESULTS In a mouse model of CDI challenge,single daily doses of ADS024 were as efficacious as multiple daily doses in protecting against subsequent challenge by C.difficile pathogen-induced disease.ADS024 showed no evidence of colonization based on the observation that the ADS024 colonies were not recovered 24 h after single doses in mice or 72 h after single doses in miniature swine.In a 28-d repeat-dose study in miniature swine,ADS024 was not detected in fecal samples using plating and qPCR methods.Phylogenetic analysis performed in the human distal colon model showed that ADS024 had a selective impact on the healthy human colonic microbiota,similarly to the in vivo studies performed in miniature swine.Safety assessments indicated that ADS024 was susceptible to all the antibiotics tested,while in silico testing revealed a low potential for off-target activity or virulence and antibioticresistance mechanisms.CONCLUSION Our findings,demonstrating in vivo efficacy of ADS024 in protecting against CDI challenge in mouse models,support the use of ADS024 in preventing recurrent CDI following standard antibiotic treatment.展开更多
The role of radiologic imaging in the investigation of irritable bowel syndrome(IBS) remains a subject of debate and there is some evidence, from recent studies of utilization of imaging in IBS, which focused on assoc...The role of radiologic imaging in the investigation of irritable bowel syndrome(IBS) remains a subject of debate and there is some evidence, from recent studies of utilization of imaging in IBS, which focused on associated costs and radiation exposure, that imaging is being used relatively widely in these patients. This review aims to assess current best evidence to accurately define the role of radiologic imaging in IBS patients. Primary and secondary literature searches were performed. Evidence suggests that the lack of "red flag" or alarm features in IBS patients should reassure the clinician that the diagnosis of IBS is correct and United States and United Kingdom guidelines recommend no radiologic imaging for IBS patients if alarm features are not present. In patients presenting with IBS symptoms and alarm features, radiologic testing may be used to exclude an alternative diagnosis and the imaging modality should be chosen based on the most likely alternative diagnosis.展开更多
Horizontal gene transfer(HGT)in the microbiome has profound consequences for human health and disease.The spread of antibiotic resistance genes,virulence,and pathogenicity determinants predominantly occurs by way of H...Horizontal gene transfer(HGT)in the microbiome has profound consequences for human health and disease.The spread of antibiotic resistance genes,virulence,and pathogenicity determinants predominantly occurs by way of HGT.Evidence exists of extensive horizontal transfer in the human gut microbiome.Phage transduction is a type of HGT event in which a bacteriophage transfers non-viral DNA from one bacterial host cell to another.The abundance of tailed bacteriophages in the human gut suggests that transduction could act as a significant mode of HGT in the gut microbiome.Here we review in detail the known mechanisms of phage-mediated HGT,namely specialized and generalized transduction,lateral transduction,gene-transfer agents,and molecular piracy,as well as methods used to detect phage-mediated HGT,and discuss its potential implications for the human gut microbiome.展开更多
The role of diet and nutrition in maintaining a healthy lifestyle has become a central part of chronic disease prevention(1).Chronic conditions such as cancer,Inflammatory bowel disease(IBD)and obesity are more preval...The role of diet and nutrition in maintaining a healthy lifestyle has become a central part of chronic disease prevention(1).Chronic conditions such as cancer,Inflammatory bowel disease(IBD)and obesity are more prevalent in people with poor diets(2).Food consumption is controlled by physiological systems such as the gut-microbiome and distinct neuroendocrine pathways that overlap to promote host nutritional gain resulting in people living longer healthier lives(3).A recent analysis of the global burden of disease by the World Health Organization(WHO),noted that factors associated with poor diet,including obesity and malnutrition,critically undermine health and wellbeing.They note that undernutrition,deficiencies in key nutrients and obesity have high social and economic impacts.Cardiovascular disease,cancer,diabetes,and respiratory diseases account for 77%of all diseases and are responsible for 86%of all premature deaths(4).There is an appreciation that diets that reduce or eliminate red meats and animal fats results in the reduction of many of the indicators of poor diet,such as body mass index(BMI)and levels of cholesterol in the blood.展开更多
基金supported by the National Natural Science Foundation of China (32021005, 31820103010)111 project (BP0719028)the Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province。
文摘Lactobacillus are considered promising therapeutic methods for nonalcoholic fatty liver disease(NAFLD).The effects of two strains of Ltmosilactobacillus mucosae on NAFLD were investigated in this study.Fourweek-old male C57BL/6J mice were divided into 4 groups(n=8 per group,Control,Model,FZJTZ26M3,FGSYC17L3).L.mucosae FZJTZ26M3 reduced the mice 's body weight,liver weight,and adipose tissue weight after 12 weeks of therapy.According to serum analysis,total cholesterol,triacylglycerol,and low-density lipoprotein cholesterol significantly decreased after L.mucosae FZJTZ26M3 intervention.Liver pathology showed that L.mucosae FZJTZ26M3 was effective to ameliorate lipid deposition in NAFLD mice.Additionally,the expression of the gene related to lipid metabolism in the liver and adipose tissue was analyzed,and the results indicated that L.mucosae FZJTZ26M3 could alleviate NAFLD by regulating lipid metabolism.Furthermore,the results of 16S rRNA gene sequencing revealed a drop in the relative abundance of Ruminococcaceae,which is linked to inflammation,but the relative abundance of a potential probiotic Akkermansia significantly increased after L.mucosae FZJTZ26M3 intervention.Generally,L.mucosae FZJTZ26M3 could be a candidate to prevent NAFLD.
文摘Crohn’s disease(CD)is an inflammatory bowel disease characterized by immunemediated flares affecting any region of the intestine alternating with remission periods.In CD,the ileum is frequently affected and about one third of patients presents with a pure ileal type.Moreover,the ileal type of CD presents epidemiological specificities like a younger age at onset and often a strong link with smoking and genetic susceptibility genes.Most of these genes are associated with Paneth cell dysfunction,a cell type found in the intestinal crypts of the ileum.Besides,a Western-type diet is associated in epidemiological studies with CD onset and increasing evidence shows that diet can modulate the composition of bile acids and gut microbiota,which in turn modulates the susceptibility of the ileum to inflammation.Thus,the interplay between environmental factors and the histological and anatomical features of the ileum is thought to explain the specific transcriptome profile observed in CD ileitis.Indeed,both immune response and cellular healing processes harbour differences between ileal and non-ileal CD.Taken together,these findings advocate for a dedicated therapeutic approach to managing ileal CD.Currently,interventional pharmacological studies have failed to clearly demonstrate distinct response profiles according to disease site.However,the high rate of stricturing disease in ileal CD requires the identification of new therapeutic targets to significantly change the natural history of this debilitating disease.
文摘BACKGROUND The Centers for Disease Control and Prevention estimate that Clostridioides difficile(C.difficile)causes half a million infections(CDI)annually and is a major cause of total infectious disease death in the United States,causing inflammation of the colon and potentially deadly diarrhea.We recently reported the isolation of ADS024,a Bacillus velezensis(B.velezensis)strain,which demonstrated direct in vitro bactericidal activity against C.difficile,with minimal collateral impact on other members of the gut microbiota.In this study,we hypothesized that in vitro activities of ADS024 will translate in vivo to protect against CDI challenge in mouse models.AIM To investigate the in vivo efficacy of B.velezensis ADS024 in protecting against CDI challenge in mouse models.METHODS To mimic disruption of the gut microbiota,the mice were exposed to vancomycin prior to dosing with ADS024.For the mouse single-dose study,the recovery of ADS024 was assessed via microbiological analysis of intestinal and fecal samples at 4 h,8 h,and 24 h after a single oral dose of 5×108 colony-forming units(CFU)/mouse of freshly grown ADS024.The single-dose study in miniature swine included groups that had been pre-dosed with vancomycin and that had been exposed to a dose range of ADS024,and a group that was not pre-dosed with vancomycin and received a single dose of ADS024.The ADS024 colonies[assessed by quantitative polymerase chain reaction(qPCR)using ADS024-specific primers]were counted on agar plates.For the 28-d miniature swine study,qPCR was used to measure ADS024 levels from fecal samples after oral administration of ADS024 capsules containing 5×109 CFU for 28 consecutive days,followed by MiSeq compositional sequencing and bioinformatic analyses to measure the impact of ADS024 on microbiota.Two studies were performed to determine the efficacy of ADS024 in a mouse model of CDI:Study 1 to determine the effects of fresh ADS024 culture and ADS024 spore preparations on the clinical manifestations of CDI in mice,and Study 2 to compare the efficacy of single daily doses vs dosing 3 times per day with fresh ADS024.C.difficile challenge was performed 24 h after the start of ADS024 exposure.To model the human distal colon,an anerobic fecal fermentation system was used.MiSeq compositional sequencing and bioinformatic analyses were performed to measure microbiota diversity changes following ADS024 treatment.To assess the potential of ADS024 to be a source of antibiotic resistance,its susceptibility to 18 different antibiotics was tested.RESULTS In a mouse model of CDI challenge,single daily doses of ADS024 were as efficacious as multiple daily doses in protecting against subsequent challenge by C.difficile pathogen-induced disease.ADS024 showed no evidence of colonization based on the observation that the ADS024 colonies were not recovered 24 h after single doses in mice or 72 h after single doses in miniature swine.In a 28-d repeat-dose study in miniature swine,ADS024 was not detected in fecal samples using plating and qPCR methods.Phylogenetic analysis performed in the human distal colon model showed that ADS024 had a selective impact on the healthy human colonic microbiota,similarly to the in vivo studies performed in miniature swine.Safety assessments indicated that ADS024 was susceptible to all the antibiotics tested,while in silico testing revealed a low potential for off-target activity or virulence and antibioticresistance mechanisms.CONCLUSION Our findings,demonstrating in vivo efficacy of ADS024 in protecting against CDI challenge in mouse models,support the use of ADS024 in preventing recurrent CDI following standard antibiotic treatment.
文摘The role of radiologic imaging in the investigation of irritable bowel syndrome(IBS) remains a subject of debate and there is some evidence, from recent studies of utilization of imaging in IBS, which focused on associated costs and radiation exposure, that imaging is being used relatively widely in these patients. This review aims to assess current best evidence to accurately define the role of radiologic imaging in IBS patients. Primary and secondary literature searches were performed. Evidence suggests that the lack of "red flag" or alarm features in IBS patients should reassure the clinician that the diagnosis of IBS is correct and United States and United Kingdom guidelines recommend no radiologic imaging for IBS patients if alarm features are not present. In patients presenting with IBS symptoms and alarm features, radiologic testing may be used to exclude an alternative diagnosis and the imaging modality should be chosen based on the most likely alternative diagnosis.
基金financial support from Science Foundation Ireland[grant number SFI/12/RC/2273_P2]and Wellcome Trust under a Wellcome Trust Research Career Development Fellowship[220646/Z/20/Z](A.N.S.)whole,or in part,by the Wellcome Trust[220646/Z/20/Z].
文摘Horizontal gene transfer(HGT)in the microbiome has profound consequences for human health and disease.The spread of antibiotic resistance genes,virulence,and pathogenicity determinants predominantly occurs by way of HGT.Evidence exists of extensive horizontal transfer in the human gut microbiome.Phage transduction is a type of HGT event in which a bacteriophage transfers non-viral DNA from one bacterial host cell to another.The abundance of tailed bacteriophages in the human gut suggests that transduction could act as a significant mode of HGT in the gut microbiome.Here we review in detail the known mechanisms of phage-mediated HGT,namely specialized and generalized transduction,lateral transduction,gene-transfer agents,and molecular piracy,as well as methods used to detect phage-mediated HGT,and discuss its potential implications for the human gut microbiome.
文摘The role of diet and nutrition in maintaining a healthy lifestyle has become a central part of chronic disease prevention(1).Chronic conditions such as cancer,Inflammatory bowel disease(IBD)and obesity are more prevalent in people with poor diets(2).Food consumption is controlled by physiological systems such as the gut-microbiome and distinct neuroendocrine pathways that overlap to promote host nutritional gain resulting in people living longer healthier lives(3).A recent analysis of the global burden of disease by the World Health Organization(WHO),noted that factors associated with poor diet,including obesity and malnutrition,critically undermine health and wellbeing.They note that undernutrition,deficiencies in key nutrients and obesity have high social and economic impacts.Cardiovascular disease,cancer,diabetes,and respiratory diseases account for 77%of all diseases and are responsible for 86%of all premature deaths(4).There is an appreciation that diets that reduce or eliminate red meats and animal fats results in the reduction of many of the indicators of poor diet,such as body mass index(BMI)and levels of cholesterol in the blood.
