Immune-related adverse events(irAEs)are complications of the use of immune checkpoint inhibitors(ICIs).ICI-associated gastritis is one of the main irAEs.The gastric microbiota is often related to the occurrence and de...Immune-related adverse events(irAEs)are complications of the use of immune checkpoint inhibitors(ICIs).ICI-associated gastritis is one of the main irAEs.The gastric microbiota is often related to the occurrence and development of many gastric diseases.Gastric microbiota adjustment may be used to treat gastric disorders in the future.Faecal microbiota transplantation can alter the gut microbiota of patients and has been used for treating ICI-associated colitis.Therefore,we propose gastric microbiota transplantation as a supplementary treatment for patients with ICI-associated gastritis who do not respond well to conventional therapy.展开更多
Helicobacter pylori infection(Hp-I)represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related fac...Helicobacter pylori infection(Hp-I)represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related factors,leading to inflammatory changes,dysbiosis and eventually gastric cancer.The normal gastric microbiota shows diversity,with Proteobacteria[Helicobacter pylori(H.pylori)belongs to this family],Firmicutes,Actinobacteria,Bacteroides and Fusobacteria being the most abundant phyla.Most studies indicate that H.pylori has inhibitory effects on the colonization of other bacteria,harboring a lower diversity of them in the stomach.When comparing the healthy with the diseased stomach,there is a change in the composition of the gastric microbiome with increasing abundance of H.pylori(where present)in the gastritis stage,while as the gastric carcinogenesis cascade progresses to gastric cancer,the oral and intestinal-type pathogenic microbial strains predominate.Hp-I creates a premalignant environment of atrophy and intestinal metaplasia and the subsequent alteration in gastric microbiota seems to play a crucial role in gastric tumorigenesis itself.Successful H.pylori eradication is suggested to restore gastric microbiota,at least in primary stages.It is more than clear that Hp-I,gastric microbiota and gastric cancer constitute a challenging tangle and the strong interaction between them makes it difficult to unroll.Future studies are considered of crucial importance to test the complex interaction on the modulation of the gastric microbiota by H.pylori as well as on the relationships between the gastric microbiota and gastric carcinogenesis.展开更多
BACKGROUND Helicobacter pylori(H.pylori)is an important pathogen that can cause a variety of diseases.Yet,full eradication of H.pylori remains a significant challenge in clinical practice.H.pylori and other microbial ...BACKGROUND Helicobacter pylori(H.pylori)is an important pathogen that can cause a variety of diseases.Yet,full eradication of H.pylori remains a significant challenge in clinical practice.H.pylori and other microbial communities have complex interactions in the unique gastric microecological environment.However,it is not clear whether the interactions have any effect on the therapeutic effect of H.pylori.AIM The aim was to investigate the characteristics of the gastric microbiota with H.pylori infection and the influence on the H.pylori eradication treatment.METHODS Patients with H.pylori infection underwent gastroscopy and received treatment for eradication.The prescription included esomeprazole 20 mg bid,Livzon Dele 220 mg bid,amoxicillin 1000 mg bid,and clarithromycin 500 mg bid for 14 d.Patients who did not respond to treatment and failed eradication were compared with those who achieved eradication by 1:2 propensity matching.Highthroughput sequencing of the gastric mucosal microbiota was performed,and the results were evaluated by alpha diversity analysis,beta diversity analysis,species correlation analysis,and metabolic pathway correlation analysis.RESULTS The eradication rate of all the patients was 95.5%(171/179).Twenty-four patients were enrolled in the study after propensity-matched scoring.There were eight cases in the failure group(patients who did not respond well to therapy)and 16 cases in the success group.The majority phyla in the two groups were the same,and included Proteobacteria,Bacteroides,Firmicutes,Actinomycetes,and Fusobacteria.The microbial diversity in the failure group had a decreasing trend(P=0.092)and the species abundance was significantly lower(P=0.031)compared with the success group.The high rate of H.pylori eradication was associated with Rhodococcus,Lactobacillus,and Sphingomonas,as they were significantly enriched in the successful group(P<0.05).Veronococcus and Cilium were enriched in the mucosa of chronic atrophic gastritis patients compared with chronic superficial gastritis patients(P=0.0466 and 0.0122,respectively).In both study groups,H.pylori was negatively correlated with other bacterial genera.More bacterial genera were directly related to H.pylori in the successful group compared with the failure group.CONCLUSION The effectiveness of quadruple H.pylori eradication therapy containing bismuth depended on gastric microbiota,and the high rate of H.pylori eradication was associated with the presence of Rhodococcus,Lactobacillus,and Sphingomonas.展开更多
Background Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry.Diarrhea and gut dysbiosis may in part be pre...Background Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry.Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut.To secure better postnatal gut colonization,we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period.Our objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli(ETEC).Methods Seventy-two 1-day-old piglets were randomized to four groups:colonic microbiota transplantation(CMT,n=18),colonic content filtrate transplantation(CcFT,n=18),gastric microbiota transplantation(GMT,n=18),or saline(CON,n=18).Inoculations were given on d 2 and 3 of life,and all piglets were milk-fed until weaning(d 20)and shortly after challenged with ETEC(d 24).We assessed growth,diarrhea prevalence,ETEC concentration,organ weight,blood parameters,small intestinal morphology and histology,gut mucosal function,and microbiota composition and diversity.Results Episodes of diarrhea were seen in all groups during both the milk-and the solid-feeding phase,possibly due to stress associated with single housing.However,CcFT showed lower diarrhea prevalence on d 27,28,and 29 compared to CON(all P<0.05).CcFT also showed a lower ETEC prevalence on d 27(P<0.05).CMT showed a higher alpha diversity and a difference in beta diversity compared to CON(P<0.05).Growth and other paraclinical endpoints were similar across groups.Conclusion In conclusion,only CcFT reduced ETEC-related post-weaning diarrhea.However,the protective effect was marginal,suggesting that higher doses,more effective modalities of administration,longer treatment periods,and better donor quality should be explored by future research to optimize the protective effects of transplantation.展开更多
Fusobacterium nucleatum(F.nucleatum)is a Gram-negative anaerobic bacterium that plays a key role in the development of oral inflammation,such as periodontitis and gingivitis.In the last 10 years,F.nucleatum has been i...Fusobacterium nucleatum(F.nucleatum)is a Gram-negative anaerobic bacterium that plays a key role in the development of oral inflammation,such as periodontitis and gingivitis.In the last 10 years,F.nucleatum has been identified as a prevalent bacterium associated with colorectal adenocarcinoma and has also been linked to cancer progression,metastasis and poor disease outcome.While the role of F.nucleatum in colon carcinogenesis has been intensively studied,its role in gastric carcinogenesis is still poorly understood.Although Helicobacter pylori infection has histo-rically been recognized as the strongest risk factor for the development of gastric cancer(GC),with recent advances in DNA sequencing technology,other members of the gastric microbial community,and F.nucleatum in particular,have received increasing attention.In this review,we summarize the existing knowledge on the involvement of F.nucleatum in gastric carcinogenesis and address the potential translational and clinical significance of F.nucleatum in GC.展开更多
There are a large number of bacteria inhabiting the human body,which provide benefits for the health.Alterations of microbiota participate in the pathogenesis of diseases.The gastric microbiota consists of bacteria fr...There are a large number of bacteria inhabiting the human body,which provide benefits for the health.Alterations of microbiota participate in the pathogenesis of diseases.The gastric microbiota consists of bacteria from seven to eleven phyla,predominantly Proteobacteria,Firmicutes,Bacteroidetes,Actinobacteria and Fusobacteria.Intrusion by Helicobacter pylori(H.pylori)does not remarkably interrupt the composition and structure of the gastric microbiota.Absence of bacterial commensal from the stomach delays the onset of H.pylori-induced gastric cancer,while presence of artificial microbiota accelerates the carcinogenesis.Altered gastric microbiota may increase the production of N-nitroso compounds,promoting the development of gastric cancer.Further investigation of the carcinogenic mechanisms of microbiota would benefit for the prevention and management of gastric cancer.展开更多
Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the...Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains(probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori,little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines(putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism.展开更多
文摘Immune-related adverse events(irAEs)are complications of the use of immune checkpoint inhibitors(ICIs).ICI-associated gastritis is one of the main irAEs.The gastric microbiota is often related to the occurrence and development of many gastric diseases.Gastric microbiota adjustment may be used to treat gastric disorders in the future.Faecal microbiota transplantation can alter the gut microbiota of patients and has been used for treating ICI-associated colitis.Therefore,we propose gastric microbiota transplantation as a supplementary treatment for patients with ICI-associated gastritis who do not respond well to conventional therapy.
文摘Helicobacter pylori infection(Hp-I)represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related factors,leading to inflammatory changes,dysbiosis and eventually gastric cancer.The normal gastric microbiota shows diversity,with Proteobacteria[Helicobacter pylori(H.pylori)belongs to this family],Firmicutes,Actinobacteria,Bacteroides and Fusobacteria being the most abundant phyla.Most studies indicate that H.pylori has inhibitory effects on the colonization of other bacteria,harboring a lower diversity of them in the stomach.When comparing the healthy with the diseased stomach,there is a change in the composition of the gastric microbiome with increasing abundance of H.pylori(where present)in the gastritis stage,while as the gastric carcinogenesis cascade progresses to gastric cancer,the oral and intestinal-type pathogenic microbial strains predominate.Hp-I creates a premalignant environment of atrophy and intestinal metaplasia and the subsequent alteration in gastric microbiota seems to play a crucial role in gastric tumorigenesis itself.Successful H.pylori eradication is suggested to restore gastric microbiota,at least in primary stages.It is more than clear that Hp-I,gastric microbiota and gastric cancer constitute a challenging tangle and the strong interaction between them makes it difficult to unroll.Future studies are considered of crucial importance to test the complex interaction on the modulation of the gastric microbiota by H.pylori as well as on the relationships between the gastric microbiota and gastric carcinogenesis.
基金Supported by The Key Projects of Peking University Third Hospital,No.BYSY2017026.
文摘BACKGROUND Helicobacter pylori(H.pylori)is an important pathogen that can cause a variety of diseases.Yet,full eradication of H.pylori remains a significant challenge in clinical practice.H.pylori and other microbial communities have complex interactions in the unique gastric microecological environment.However,it is not clear whether the interactions have any effect on the therapeutic effect of H.pylori.AIM The aim was to investigate the characteristics of the gastric microbiota with H.pylori infection and the influence on the H.pylori eradication treatment.METHODS Patients with H.pylori infection underwent gastroscopy and received treatment for eradication.The prescription included esomeprazole 20 mg bid,Livzon Dele 220 mg bid,amoxicillin 1000 mg bid,and clarithromycin 500 mg bid for 14 d.Patients who did not respond to treatment and failed eradication were compared with those who achieved eradication by 1:2 propensity matching.Highthroughput sequencing of the gastric mucosal microbiota was performed,and the results were evaluated by alpha diversity analysis,beta diversity analysis,species correlation analysis,and metabolic pathway correlation analysis.RESULTS The eradication rate of all the patients was 95.5%(171/179).Twenty-four patients were enrolled in the study after propensity-matched scoring.There were eight cases in the failure group(patients who did not respond well to therapy)and 16 cases in the success group.The majority phyla in the two groups were the same,and included Proteobacteria,Bacteroides,Firmicutes,Actinomycetes,and Fusobacteria.The microbial diversity in the failure group had a decreasing trend(P=0.092)and the species abundance was significantly lower(P=0.031)compared with the success group.The high rate of H.pylori eradication was associated with Rhodococcus,Lactobacillus,and Sphingomonas,as they were significantly enriched in the successful group(P<0.05).Veronococcus and Cilium were enriched in the mucosa of chronic atrophic gastritis patients compared with chronic superficial gastritis patients(P=0.0466 and 0.0122,respectively).In both study groups,H.pylori was negatively correlated with other bacterial genera.More bacterial genera were directly related to H.pylori in the successful group compared with the failure group.CONCLUSION The effectiveness of quadruple H.pylori eradication therapy containing bismuth depended on gastric microbiota,and the high rate of H.pylori eradication was associated with the presence of Rhodococcus,Lactobacillus,and Sphingomonas.
基金support by European Union's Horizon 2020 Research and Innovation Program under Grant Agreement No.862829,project AVANT-Alternatives to Veterinary ANTimicrobials.
文摘Background Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry.Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut.To secure better postnatal gut colonization,we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period.Our objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli(ETEC).Methods Seventy-two 1-day-old piglets were randomized to four groups:colonic microbiota transplantation(CMT,n=18),colonic content filtrate transplantation(CcFT,n=18),gastric microbiota transplantation(GMT,n=18),or saline(CON,n=18).Inoculations were given on d 2 and 3 of life,and all piglets were milk-fed until weaning(d 20)and shortly after challenged with ETEC(d 24).We assessed growth,diarrhea prevalence,ETEC concentration,organ weight,blood parameters,small intestinal morphology and histology,gut mucosal function,and microbiota composition and diversity.Results Episodes of diarrhea were seen in all groups during both the milk-and the solid-feeding phase,possibly due to stress associated with single housing.However,CcFT showed lower diarrhea prevalence on d 27,28,and 29 compared to CON(all P<0.05).CcFT also showed a lower ETEC prevalence on d 27(P<0.05).CMT showed a higher alpha diversity and a difference in beta diversity compared to CON(P<0.05).Growth and other paraclinical endpoints were similar across groups.Conclusion In conclusion,only CcFT reduced ETEC-related post-weaning diarrhea.However,the protective effect was marginal,suggesting that higher doses,more effective modalities of administration,longer treatment periods,and better donor quality should be explored by future research to optimize the protective effects of transplantation.
基金Supported by The European Union’s“Horizon Europe Framework Program”Grant Agreement,No.101095359(AIDA project under the call"HORIZON-HLTH-2022-STAYHLTH-02).
文摘Fusobacterium nucleatum(F.nucleatum)is a Gram-negative anaerobic bacterium that plays a key role in the development of oral inflammation,such as periodontitis and gingivitis.In the last 10 years,F.nucleatum has been identified as a prevalent bacterium associated with colorectal adenocarcinoma and has also been linked to cancer progression,metastasis and poor disease outcome.While the role of F.nucleatum in colon carcinogenesis has been intensively studied,its role in gastric carcinogenesis is still poorly understood.Although Helicobacter pylori infection has histo-rically been recognized as the strongest risk factor for the development of gastric cancer(GC),with recent advances in DNA sequencing technology,other members of the gastric microbial community,and F.nucleatum in particular,have received increasing attention.In this review,we summarize the existing knowledge on the involvement of F.nucleatum in gastric carcinogenesis and address the potential translational and clinical significance of F.nucleatum in GC.
文摘There are a large number of bacteria inhabiting the human body,which provide benefits for the health.Alterations of microbiota participate in the pathogenesis of diseases.The gastric microbiota consists of bacteria from seven to eleven phyla,predominantly Proteobacteria,Firmicutes,Bacteroidetes,Actinobacteria and Fusobacteria.Intrusion by Helicobacter pylori(H.pylori)does not remarkably interrupt the composition and structure of the gastric microbiota.Absence of bacterial commensal from the stomach delays the onset of H.pylori-induced gastric cancer,while presence of artificial microbiota accelerates the carcinogenesis.Altered gastric microbiota may increase the production of N-nitroso compounds,promoting the development of gastric cancer.Further investigation of the carcinogenic mechanisms of microbiota would benefit for the prevention and management of gastric cancer.
文摘Gastric cancer is still the second leading cause of cancer death worldwide, accounting for about 10% of newly diagnosed neoplasms. In the last decades, an emerging role has been attributed to the relations between the intestinal microbiota and the onset of both gastrointestinal and non-gastrointestinal neoplasms. Thus, exogenous microbial administration of peculiar bacterial strains(probiotics) has been suggested as having a profound influence on multiple processes associated with a change in cancer risk. The internationally accepted definition of probiotics is live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The possible effects on the gastrointestinal tract following probiotic administration have been investigated in vitro and in animal models, as well as in healthy volunteers and in patients suffering from different human gastrointestinal diseases. Although several evidences are available on the use of probiotics against the carcinogen Helicobacter pylori,little is still known about the potential cross-interactions among probiotics, the composition and quality of intestinal flora and the neoplastic transformation of gastric mucosa. In this connection, a significant role in cell proliferation is played by polyamines(putrescine, spermidine, and spermine). These small amines are required in both pre-neoplastic and neoplastic tissue to sustain the cell growth and the evidences here provided suggest that probiotics may act as antineoplastic agents in the stomach by affecting also the polyamine content and functions. This review will summarize data on the most widely recognized effects of probiotics against neoplastic transformation of gastric mucosa and in particular on their ability in modulating cell proliferation, paying attention to the polyamine metabolism.
基金National Natural Science Foundation of China (81473458)Chinese Medicine Science and Technology Program of Jiangsu Province (MS2021003)Jiangsu Province Phase V"333"Scientific Research Project (BRA2020164)。