AIM: To assess the safety of Bifidobacterium/ongum (B. longum) JDM301 based on complete genome sequences. METHODS: The complete genome sequences of JDM301 were determined using the GS 20 system. Putative virulence...AIM: To assess the safety of Bifidobacterium/ongum (B. longum) JDM301 based on complete genome sequences. METHODS: The complete genome sequences of JDM301 were determined using the GS 20 system. Putative virulence factors, putative antibiotic resis- tance genes and genes encoding enzymes respon- sible for harmful metabolites were identified by blast with virulence factors database, antibiotic resistance genes database and genes associated with harmful metabolites in previous reports. Minimum inhibitory concentration of 16 common antimicrobial agents was evaluated by E-test RESULTS: JDM301 was shown to contain 36 genes as- sociated with antibiotic resistance, 5 enzymes related to harmful metabolites and 162 nonspecific virulence fac- tors mainly associated with transcriptional regulation, adhesion, sugar and amino acid transport. B. longum JDM301 was intrinsically resistant to ciprofloxacin, ami- kacin, gentamicin and streptomycin and susceptible to vancomycin, amoxicillin, cephalothin, chloramphenicol, erythromycin, ampicillin, cefotaxime, rifampicin, imi- penem and trimethoprim-sulphamethoxazol. JDM301 was moderately resistant to bacitracin, while an earlier study showed that bifidobacteria were susceptible to this antibiotic. A tetracycline resistance gene with the risk of transfer was found in JDM301, which needs to be experimentally validated. CONCLUSION: The safety assessment of JDM301 using information derived from complete bacterial ge- nome will contribute to a wider and deeper insight into the safety of probiotic bacteria.展开更多
BACKGROUND Bifidobacterium longum 35624 has shown efficacy in improving irritable bowel syndrome(IBS)symptoms compared with placebo in double-blind randomized studies.However,few data are available from real-life clin...BACKGROUND Bifidobacterium longum 35624 has shown efficacy in improving irritable bowel syndrome(IBS)symptoms compared with placebo in double-blind randomized studies.However,few data are available from real-life clinical practice or from studies that used Rome IV criteria to diagnose IBS.AIM To assess the effect of B.longum 35624 on IBS severity and quality of life in a reallife setting.METHODS From November 2018 to January 2020,278 patients with IBS(according to Rome IV criteria)were enrolled in a prospective,open-label,multicenter observational study by private practice gastroenterologists to received one capsule of B.longum 35624(10^(9) colony-forming units)per day for 30 d.Participation in the study was independently proposed to patients during spontaneous consultations.Disease severity(assessed by the IBS severity scoring system)and patient quality of life(assessed by the IBS quality of life questionnaire)were compared between the inclusion visit(baseline)and the visit at the end of 30 d of treatment.The characteristics of patients were described at baseline.Continuous variables comparisons between inclusion and end-of-treatment visits were performed using the t-test and Kruskal-Wallis test.Categorical variables comparisons were performed using theχ^(2) test.RESULTSA total of 233 patients,with a mean age of 51.4 years and composed of 71.2%women,were included in the study.Of these patients,48.1%had moderate IBS and 46.4%had severe IBS.After a 30-d treatment period with one B.longum 35624 capsule per day,a significant decrease in IBS severity was observed compared to baseline(mean±SD,IBS severity scoring system scores:208±104 vs 303±81,P<0.001)and 57%of patients moved to lower severity categories or achieved remission.The quality of life of patients was also improved by the treatment(IBS Quality of Life questionnaire score:68.8±20.9 vs 60.2±20.5;P<0.001)and 63.8%of patients were satisfied with the treatment.CONCLUSION Thirty days of treatment with B.longum 35624 reduces disease severity and improves the quality of life of patients with IBS,particularly those with the most severe forms of IBS.展开更多
Most scientific investigations regarding inflammatory bowel disease(IBD)pathogenesis or therapeutic strategies use dextran sulfate sodium(DSS)-induced models performed on mice.However,differences between human and ani...Most scientific investigations regarding inflammatory bowel disease(IBD)pathogenesis or therapeutic strategies use dextran sulfate sodium(DSS)-induced models performed on mice.However,differences between human and animal microbiota may confound the data reproducibility from rodent experiments to clinical trials.In this study,the intervention effects of Bifidobacterium longum NSP001 on DSS-induced colitis were investigated using mice colonized with either native or humanised microbiota.Disorders in disease activity index(DAI),morphology and histology of colon tissue,intestinal permeability,and secretion of MPO,TNF-αand IL-6 were ameliorated by daily intake of live B.longum NSP001 cells in both conventional and humanised colitis mice.But the abnormal thymus index,and colonic production of ZO-1 and iNOS were improved only in colitis mice treated with B.longum NSP001 and humanised microbiome.The accumulation of acetic acid and propionic acid in colon microbiome,and the optimization of primary bile acid biosynthesis and glycerophospholipid metabolism pathways in cecum commensals were likely to explain the beneficial effects of B.longum NSP001.These data revealed that intestinal microbiome baseline would possibly affect the manifestation features of interventions by probiotics or dietary components and highlighted the necessity to include humanised microbiome while investigating potential therapeutic strategies based on rodent models.展开更多
An increasing number of studies have indicated that gut microbiota and its metabolites are crucial in the development of hyperlipidemia.Bifidobacterium longum(B.longum)CCFM1077 has been shown to have lipid-lowering ef...An increasing number of studies have indicated that gut microbiota and its metabolites are crucial in the development of hyperlipidemia.Bifidobacterium longum(B.longum)CCFM1077 has been shown to have lipid-lowering effects in animals.This study aimed to evaluate the potential of B.longum CCFM1077 in lowering the lipid levels in patients with hyperlipidemia and investigate the effect of this bacterium on serum lipid abnormalities,gut microbiota,and fecal metabolites in these patients.This study was a six-week,randomized,double-blind,and placebo-controlled pilot clinical trial.Subjects with hyperlipidemia(N=62)were randomly assigned to receive placebo(N=31)or B.longum CCFM1077(1×1010colony-forming units(CFUs)per day;N=31).Serum lipid levels including total cholesterol(TC),lowdensity lipoprotein cholesterol(LDL-C),total triglyceride(TG),and high-density lipoprotein cholesterol(HDL-C)were examined at the baseline and interventio nal endpoints.Changes in the gut microbiota composition and diversity were measured based on 16S ribosomal RNA(rRNA)sequencing of the V3-V4region at the end of the intervention period.Non-targeted metabolomics of the feces was performed using ultra-performance liquid chromatography(UPLC)-Q-Exactive Orbitrap/mass spectrometer.Oral administration of B.longum CCFM1077 for six weeks significantly decreased the serum levels of TC(p<0.01)and LDL-C(p<0.01)in patients with hyperlipidemia.B.longum CCFM1077 treatment markedly increased gut microbiota diversity and the relative abundance of anti-obesity-related genera,including Lactobacillus,Butyricicoccus,Bifidobacterium,and Blautia,whereas it decreased the relative abundance of obesity-related genera,including Alistipes,Megamonas,and Catenibacterium.Additionally,some key metabolites(bile acids(BAs),biotin,and caffeine)and their corresponding metabolic pathways(primary BA biosynthesis,and taurine and hypotaurine,biotin,purine,and caffeine metabolisms)were enriched by B.longum CCFM1077,and thus it may lower lipid levels.B.longum CCFM1077 is a probiotic strain with the potential to lower serum TC and LDL-C levels patients with hyperlipidemia.The underlying mechanism may be related to the increased abundance of anti-obesity-related genera and fecal metabolites.These findings provide a foundation for future clinical applications of lipid-lowering probiotics in managing individuals with hyperlipidemia.展开更多
Heat-killed Bifidobacterium longum CLA8013 has been demonstrated to improve the frequency of defecation, straining, and pain during defecation in human placebo-controlled, double-blind, parallel-group studies. We cond...Heat-killed Bifidobacterium longum CLA8013 has been demonstrated to improve the frequency of defecation, straining, and pain during defecation in human placebo-controlled, double-blind, parallel-group studies. We conducted a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety of both long-term and excessive intakes of heat-killed B. longum CLA8013, when used as a food with functional claims. In both tests, 30 healthy volunteers were divided into two groups: an active group that ingested heat-killed B. longum CLA8013 and a placebo group. In the long-term intake safety study, participants in the active group ingested 25 billion cells/day for 12 weeks. In the excessive intake safety study, participants in the active group ingested 125 billion cells/day for 4 weeks. Physical, hematological, biochemical, and urine examinations were conducted, and adverse events were evaluated in both studies. The studies revealed no abnormalities in any of the safety tests. In conclusion, no safety-related issues were identified with long-term or excessive intake of heat-killed B. longum CLA8013.展开更多
AIM:To investigate the effects of the probiotic Bifidobacterium longum BB536 on the health management of elderly patients receiving enteral feeding.METHODS:Two double-blind,placebo-controlled trials were performed wit...AIM:To investigate the effects of the probiotic Bifidobacterium longum BB536 on the health management of elderly patients receiving enteral feeding.METHODS:Two double-blind,placebo-controlled trials were performed with long-term inpatients receiving enteral tube feeding at Kitakyushu Hospital Group,Fukuoka,Japan.BB536 was administered as BB536-L and BB536-H powders that contained approximately 2.5 × 10 10 and 5 × 10 10 cfu of BB536,respectively.In the first trial,83 patients(age range:67-101 years) were randomized into 2 groups that received placebo(placebo group) or BB536-H(BB536 group) powders.In the second trial,123 patients(age range:65-102years) were randomized into 3 groups,and each group received placebo(placebo group),BB536-L(BB536-L group),or BB536-H(BB536-H group) powders.Each patient received the study medication for 16 wk after 1 wk of pre-observation.Fecal samples were collected from each patient prior to and after the intervention during Trial 2.Clinical observations included body temperature,occurrence of infection,frequency of defecation,and fecal microbiota.RESULTS:No significant changes were observed in the frequency of defecation for either treatment in Trial 1.However,a significant change was noted in the BB536-L group(P = 0.0439) in Trial 2 but not in the placebo or BB536-H groups.Subgroup analyses based on the frequency of defecation for each patient during the pre-observation period for both trials revealed significant increases in bowel movements in patients with a low frequency of defecation and significant decreases in the bowel movements of patients with a high frequency of defecation during the intervention period in the BB536 groups.The combination of Trials 1 and 2 data revealed a modulatory effect of BB536 ingestion on the changes in bowel movements.Significantly increased bowel movements were observed in patients in the low frequency subgroup with significant intergroup differences(P < 0.01).Significantly decreased bowel movements were observed in patients in the high subgroup,but no significant intergroup differences were observed compared with the placebo group.BB536 ingestion increased the prevalence of normally formed stools.BB536 intake also significantly(P < 0.01) increased the cell numbers of bifidobacteria in fecal microbiota,and significant intergroup differences were observed at week 16.No adverse events were reported in any group.CONCLUSION:Our results suggest that BB536 ingestion modulated the intestinal environment and may have improved the health care of elderly patients receiving enteral feeding.展开更多
Maize straw,an abundant agricultural residue,has potential as an eco-friendly resource.The aim of this study was to investigate the struc-ture and effect on Bifidobacterium longum of exopolysaccharide produced by Weis...Maize straw,an abundant agricultural residue,has potential as an eco-friendly resource.The aim of this study was to investigate the struc-ture and effect on Bifidobacterium longum of exopolysaccharide produced by Weissella cibaria using maize straw as a carbon source.In this work,an exopolysaccharide-producing strain was isolated from vegetable juice,which was identified as W.cibaria.Our results demonstrated that exopolysaccharide produced by W.cibaria is a linear glucan containing anα-1,6 glycosidic bond with a molecular weight of 9462 Da.In addition,scanning electron microscopy of exopolysaccharide from W.cibaria revealed the flake structures.In vitro assays showed that the exopolysaccharide from W.cibaria has the ability to stimulate the proliferation of B.longum strain and its metabolism to produce acetic acid.This work provides a scientific reference for the potential application of maize straw and a new insight into an eco-friendly carbon source to produce exopolysaccharide.展开更多
基金Supported by The National Key Program for Infectious Diseases of China,No. 2008ZX10004 and 2009ZX10004the Program of Shanghai Subject Chief Scientist,No. 09XD1402700+1 种基金the Program of Shanghai Research and Development,No. 10JC1408200a China Partnering Award from the Biotechnology and Biological Sciences Research Council,United Kingdom
文摘AIM: To assess the safety of Bifidobacterium/ongum (B. longum) JDM301 based on complete genome sequences. METHODS: The complete genome sequences of JDM301 were determined using the GS 20 system. Putative virulence factors, putative antibiotic resis- tance genes and genes encoding enzymes respon- sible for harmful metabolites were identified by blast with virulence factors database, antibiotic resistance genes database and genes associated with harmful metabolites in previous reports. Minimum inhibitory concentration of 16 common antimicrobial agents was evaluated by E-test RESULTS: JDM301 was shown to contain 36 genes as- sociated with antibiotic resistance, 5 enzymes related to harmful metabolites and 162 nonspecific virulence fac- tors mainly associated with transcriptional regulation, adhesion, sugar and amino acid transport. B. longum JDM301 was intrinsically resistant to ciprofloxacin, ami- kacin, gentamicin and streptomycin and susceptible to vancomycin, amoxicillin, cephalothin, chloramphenicol, erythromycin, ampicillin, cefotaxime, rifampicin, imi- penem and trimethoprim-sulphamethoxazol. JDM301 was moderately resistant to bacitracin, while an earlier study showed that bifidobacteria were susceptible to this antibiotic. A tetracycline resistance gene with the risk of transfer was found in JDM301, which needs to be experimentally validated. CONCLUSION: The safety assessment of JDM301 using information derived from complete bacterial ge- nome will contribute to a wider and deeper insight into the safety of probiotic bacteria.
文摘BACKGROUND Bifidobacterium longum 35624 has shown efficacy in improving irritable bowel syndrome(IBS)symptoms compared with placebo in double-blind randomized studies.However,few data are available from real-life clinical practice or from studies that used Rome IV criteria to diagnose IBS.AIM To assess the effect of B.longum 35624 on IBS severity and quality of life in a reallife setting.METHODS From November 2018 to January 2020,278 patients with IBS(according to Rome IV criteria)were enrolled in a prospective,open-label,multicenter observational study by private practice gastroenterologists to received one capsule of B.longum 35624(10^(9) colony-forming units)per day for 30 d.Participation in the study was independently proposed to patients during spontaneous consultations.Disease severity(assessed by the IBS severity scoring system)and patient quality of life(assessed by the IBS quality of life questionnaire)were compared between the inclusion visit(baseline)and the visit at the end of 30 d of treatment.The characteristics of patients were described at baseline.Continuous variables comparisons between inclusion and end-of-treatment visits were performed using the t-test and Kruskal-Wallis test.Categorical variables comparisons were performed using theχ^(2) test.RESULTSA total of 233 patients,with a mean age of 51.4 years and composed of 71.2%women,were included in the study.Of these patients,48.1%had moderate IBS and 46.4%had severe IBS.After a 30-d treatment period with one B.longum 35624 capsule per day,a significant decrease in IBS severity was observed compared to baseline(mean±SD,IBS severity scoring system scores:208±104 vs 303±81,P<0.001)and 57%of patients moved to lower severity categories or achieved remission.The quality of life of patients was also improved by the treatment(IBS Quality of Life questionnaire score:68.8±20.9 vs 60.2±20.5;P<0.001)and 63.8%of patients were satisfied with the treatment.CONCLUSION Thirty days of treatment with B.longum 35624 reduces disease severity and improves the quality of life of patients with IBS,particularly those with the most severe forms of IBS.
基金The financial supports from the National Natural Science Foundation of China for Distinguished Young Scholars(31825020)the Special and General Fund of China Postdoctoral Science Foundation(2019TQ0138 and 2019M662281)the Postdoctoral Financial Support from Human Resources and Social Security Department of Jiangxi Province(2019RC13 and 2020KY23)。
文摘Most scientific investigations regarding inflammatory bowel disease(IBD)pathogenesis or therapeutic strategies use dextran sulfate sodium(DSS)-induced models performed on mice.However,differences between human and animal microbiota may confound the data reproducibility from rodent experiments to clinical trials.In this study,the intervention effects of Bifidobacterium longum NSP001 on DSS-induced colitis were investigated using mice colonized with either native or humanised microbiota.Disorders in disease activity index(DAI),morphology and histology of colon tissue,intestinal permeability,and secretion of MPO,TNF-αand IL-6 were ameliorated by daily intake of live B.longum NSP001 cells in both conventional and humanised colitis mice.But the abnormal thymus index,and colonic production of ZO-1 and iNOS were improved only in colitis mice treated with B.longum NSP001 and humanised microbiome.The accumulation of acetic acid and propionic acid in colon microbiome,and the optimization of primary bile acid biosynthesis and glycerophospholipid metabolism pathways in cecum commensals were likely to explain the beneficial effects of B.longum NSP001.These data revealed that intestinal microbiome baseline would possibly affect the manifestation features of interventions by probiotics or dietary components and highlighted the necessity to include humanised microbiome while investigating potential therapeutic strategies based on rodent models.
基金supported by the Natural Science Foundation of Jiangsu Province(BK20220155 and BE2021623)the National Natural Science Foundation of China(32021005,U1903205,and 32001665)the Key Scientific and Technological Research Projects in the Key Areas of the Xinjiang Production and Construction Corps(2018AB010)。
文摘An increasing number of studies have indicated that gut microbiota and its metabolites are crucial in the development of hyperlipidemia.Bifidobacterium longum(B.longum)CCFM1077 has been shown to have lipid-lowering effects in animals.This study aimed to evaluate the potential of B.longum CCFM1077 in lowering the lipid levels in patients with hyperlipidemia and investigate the effect of this bacterium on serum lipid abnormalities,gut microbiota,and fecal metabolites in these patients.This study was a six-week,randomized,double-blind,and placebo-controlled pilot clinical trial.Subjects with hyperlipidemia(N=62)were randomly assigned to receive placebo(N=31)or B.longum CCFM1077(1×1010colony-forming units(CFUs)per day;N=31).Serum lipid levels including total cholesterol(TC),lowdensity lipoprotein cholesterol(LDL-C),total triglyceride(TG),and high-density lipoprotein cholesterol(HDL-C)were examined at the baseline and interventio nal endpoints.Changes in the gut microbiota composition and diversity were measured based on 16S ribosomal RNA(rRNA)sequencing of the V3-V4region at the end of the intervention period.Non-targeted metabolomics of the feces was performed using ultra-performance liquid chromatography(UPLC)-Q-Exactive Orbitrap/mass spectrometer.Oral administration of B.longum CCFM1077 for six weeks significantly decreased the serum levels of TC(p<0.01)and LDL-C(p<0.01)in patients with hyperlipidemia.B.longum CCFM1077 treatment markedly increased gut microbiota diversity and the relative abundance of anti-obesity-related genera,including Lactobacillus,Butyricicoccus,Bifidobacterium,and Blautia,whereas it decreased the relative abundance of obesity-related genera,including Alistipes,Megamonas,and Catenibacterium.Additionally,some key metabolites(bile acids(BAs),biotin,and caffeine)and their corresponding metabolic pathways(primary BA biosynthesis,and taurine and hypotaurine,biotin,purine,and caffeine metabolisms)were enriched by B.longum CCFM1077,and thus it may lower lipid levels.B.longum CCFM1077 is a probiotic strain with the potential to lower serum TC and LDL-C levels patients with hyperlipidemia.The underlying mechanism may be related to the increased abundance of anti-obesity-related genera and fecal metabolites.These findings provide a foundation for future clinical applications of lipid-lowering probiotics in managing individuals with hyperlipidemia.
文摘Heat-killed Bifidobacterium longum CLA8013 has been demonstrated to improve the frequency of defecation, straining, and pain during defecation in human placebo-controlled, double-blind, parallel-group studies. We conducted a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety of both long-term and excessive intakes of heat-killed B. longum CLA8013, when used as a food with functional claims. In both tests, 30 healthy volunteers were divided into two groups: an active group that ingested heat-killed B. longum CLA8013 and a placebo group. In the long-term intake safety study, participants in the active group ingested 25 billion cells/day for 12 weeks. In the excessive intake safety study, participants in the active group ingested 125 billion cells/day for 4 weeks. Physical, hematological, biochemical, and urine examinations were conducted, and adverse events were evaluated in both studies. The studies revealed no abnormalities in any of the safety tests. In conclusion, no safety-related issues were identified with long-term or excessive intake of heat-killed B. longum CLA8013.
文摘AIM:To investigate the effects of the probiotic Bifidobacterium longum BB536 on the health management of elderly patients receiving enteral feeding.METHODS:Two double-blind,placebo-controlled trials were performed with long-term inpatients receiving enteral tube feeding at Kitakyushu Hospital Group,Fukuoka,Japan.BB536 was administered as BB536-L and BB536-H powders that contained approximately 2.5 × 10 10 and 5 × 10 10 cfu of BB536,respectively.In the first trial,83 patients(age range:67-101 years) were randomized into 2 groups that received placebo(placebo group) or BB536-H(BB536 group) powders.In the second trial,123 patients(age range:65-102years) were randomized into 3 groups,and each group received placebo(placebo group),BB536-L(BB536-L group),or BB536-H(BB536-H group) powders.Each patient received the study medication for 16 wk after 1 wk of pre-observation.Fecal samples were collected from each patient prior to and after the intervention during Trial 2.Clinical observations included body temperature,occurrence of infection,frequency of defecation,and fecal microbiota.RESULTS:No significant changes were observed in the frequency of defecation for either treatment in Trial 1.However,a significant change was noted in the BB536-L group(P = 0.0439) in Trial 2 but not in the placebo or BB536-H groups.Subgroup analyses based on the frequency of defecation for each patient during the pre-observation period for both trials revealed significant increases in bowel movements in patients with a low frequency of defecation and significant decreases in the bowel movements of patients with a high frequency of defecation during the intervention period in the BB536 groups.The combination of Trials 1 and 2 data revealed a modulatory effect of BB536 ingestion on the changes in bowel movements.Significantly increased bowel movements were observed in patients in the low frequency subgroup with significant intergroup differences(P < 0.01).Significantly decreased bowel movements were observed in patients in the high subgroup,but no significant intergroup differences were observed compared with the placebo group.BB536 ingestion increased the prevalence of normally formed stools.BB536 intake also significantly(P < 0.01) increased the cell numbers of bifidobacteria in fecal microbiota,and significant intergroup differences were observed at week 16.No adverse events were reported in any group.CONCLUSION:Our results suggest that BB536 ingestion modulated the intestinal environment and may have improved the health care of elderly patients receiving enteral feeding.
基金supported by Fujian Agriculture and Forestry University(No.72202200901),China.
文摘Maize straw,an abundant agricultural residue,has potential as an eco-friendly resource.The aim of this study was to investigate the struc-ture and effect on Bifidobacterium longum of exopolysaccharide produced by Weissella cibaria using maize straw as a carbon source.In this work,an exopolysaccharide-producing strain was isolated from vegetable juice,which was identified as W.cibaria.Our results demonstrated that exopolysaccharide produced by W.cibaria is a linear glucan containing anα-1,6 glycosidic bond with a molecular weight of 9462 Da.In addition,scanning electron microscopy of exopolysaccharide from W.cibaria revealed the flake structures.In vitro assays showed that the exopolysaccharide from W.cibaria has the ability to stimulate the proliferation of B.longum strain and its metabolism to produce acetic acid.This work provides a scientific reference for the potential application of maize straw and a new insight into an eco-friendly carbon source to produce exopolysaccharide.