AIM： To investigate the mechanisms underlying the reduction in gastric blood flow induced by a luminal water extract of Hellcobacter pylori （HPE）. METHODS： The stomachs of isoflurane-anesthetized mice were exterio...AIM： To investigate the mechanisms underlying the reduction in gastric blood flow induced by a luminal water extract of Hellcobacter pylori （HPE）. METHODS： The stomachs of isoflurane-anesthetized mice were exteriorized, and the mucosal surface exposed. Blood flow was measured with the laserDoppler technique, and systemic arterial blood pressure monitored. C57BL/6 mice were exposed to water extract produced from Hpylori strain 88-23. To investigate the role of a nerveor iNOS-mediated pathway, we used intraluminal lidocaine and iNOS-/- mice. Blood flow response to the endogenous nitric oxide synthase inhibitor asymmetric dimethyl arginine （ADMA） was also assessed. RESULTS： In wild-type mice, HPE decreased mucosal blood flow by approximately 30%. This reduction was abolished in iNOS-deficient mice, and by pre-treatment with lidocaine. Luminally applied ADMA resulted in reduction in blood flow similar to that observed in wildtype mice exposed to HPE. CONCLUSION： A H py/ori water extract reduces gastric mucosal blood flow acutely through iNOS- and nerve-mediated pathways.展开更多
Opportunistic bacteria in apical periodontitis (AP) may pose a risk for systemic dissemination.Mucosal-associated invariant T (MAIT) cells are innate-like T cells with a broad and potent antimicrobial activity importa...Opportunistic bacteria in apical periodontitis (AP) may pose a risk for systemic dissemination.Mucosal-associated invariant T (MAIT) cells are innate-like T cells with a broad and potent antimicrobial activity important for gut mucosal integrity.It was recently shown that MAIT cells are present in the oral mucosal tissue,but the involvement of MAIT cells in AP is unknown.Here,comparison of surgically resected AP and gingival tissues demonstrated that AP tissues express significantly higher levels of Vα7.2-Jα33,Vα7.2- Jα20,Vα7.2-Jα12,Cα and tumour necrosis factor (TNF),interferon (IFN)-γ and interleukin (IL)-17A transcripts,resembling a MAIT cell signature.Moreover,in AP tissues the MR1-restricted MAIT cells positive for MR1–5-OP-RU tetramer staining appeared to be of similar levels as in peripheral blood but consisted mainly of CD4^+ subset.Unlike gingival tissues,the AP microbiome was quantitatively impacted by factors like fistula and high patient age and had a prominent riboflavin-expressing bacterial feature.When merged in an integrated view,the examined immune and microbiome data in the sparse partial least squares discriminant analysis could identify bacterial relative abundances that negatively correlated with Vα7.2-Jα33,Cα,and IL-17A transcript expressions in AP,implying that MAIT cells could play a role in the local defence at the oral tissue barrier.In conclusion,we describe the presence of MAIT cells at the oral site where translocation of oral microbiota could take place.These findings have implications for understanding the immune sensing of polymicrobial-related oral diseases.展开更多
The bacterium Helicobacter pylori(H.pylori)infects the stomachs of approximately 50%of all humans.With its universal occurrence,high infectivity and virulence properties it is considered as one of the most severe glob...The bacterium Helicobacter pylori(H.pylori)infects the stomachs of approximately 50%of all humans.With its universal occurrence,high infectivity and virulence properties it is considered as one of the most severe global burdens of modern humankind.It has accompanied humans for many thousands of years,and due to its high genetic variability and vertical transmission,its population genetics reflects the history of human migrations.However,especially complex demographic events such as the colonisation of Europe cannot be resolved with population genetic analysis of modern H.pylori strains alone.This is best exemplified with the reconstruction of the 5300-year-old H.pylori genome of the Iceman,a European Copper Age mummy.Our analysis provided precious insights into the ancestry and evolution of the pathogen and underlined the high complexity of ancient European population history.In this review we will provide an overview on the molecular analysis of H.pylori in mummified human remains that were done so far and we will outline methodological advancements in the field of ancient DNA research that support the reconstruction and authentication of ancient H.pylori genome sequences.展开更多
The role of the human intestinal tract in host–microbe interactions has been highlighted in recent years.Several 3-dimensional(3D)models have been developed to reproduce the physiological characteristics of the human...The role of the human intestinal tract in host–microbe interactions has been highlighted in recent years.Several 3-dimensional(3D)models have been developed to reproduce the physiological characteristics of the human gut and to investigate the function of the gut microbiota.One challenge for 3D models is to recapitulate the low oxygen concentrations in the intestinal lumen.Moreover,most earlier 3D culture systems used a membrane to physically separate bacteria from the intestinal epithelium,which has sometimes made the studies of bacteria adhering to or invading cells less feasible.We report the establishment of a 3D gut epithelium model and cultured it at high cell viability under an anaerobic condition.We further cocultured intestinal bacteria including both commensal and pathogen directly with epithelial cells in the established 3D model under the anaerobic condition.We subsequently compared the gene expression differences of aerobic and anaerobic conditions for cell and bacterial growth via dual RNA sequencing.Our study provides a physiologically relevant 3D gut epithelium model that mimics the anaerobic condition in the intestinal lumen and supplies a powerful system for future in-depth gut–microbe interactional investigations.展开更多
基金Supported by The Swedish Research Council (08646), Envirotainer Holding AB
文摘AIM： To investigate the mechanisms underlying the reduction in gastric blood flow induced by a luminal water extract of Hellcobacter pylori （HPE）. METHODS： The stomachs of isoflurane-anesthetized mice were exteriorized, and the mucosal surface exposed. Blood flow was measured with the laserDoppler technique, and systemic arterial blood pressure monitored. C57BL/6 mice were exposed to water extract produced from Hpylori strain 88-23. To investigate the role of a nerveor iNOS-mediated pathway, we used intraluminal lidocaine and iNOS-/- mice. Blood flow response to the endogenous nitric oxide synthase inhibitor asymmetric dimethyl arginine （ADMA） was also assessed. RESULTS： In wild-type mice, HPE decreased mucosal blood flow by approximately 30%. This reduction was abolished in iNOS-deficient mice, and by pre-treatment with lidocaine. Luminally applied ADMA resulted in reduction in blood flow similar to that observed in wildtype mice exposed to HPE. CONCLUSION： A H py/ori water extract reduces gastric mucosal blood flow acutely through iNOS- and nerve-mediated pathways.
文摘Opportunistic bacteria in apical periodontitis (AP) may pose a risk for systemic dissemination.Mucosal-associated invariant T (MAIT) cells are innate-like T cells with a broad and potent antimicrobial activity important for gut mucosal integrity.It was recently shown that MAIT cells are present in the oral mucosal tissue,but the involvement of MAIT cells in AP is unknown.Here,comparison of surgically resected AP and gingival tissues demonstrated that AP tissues express significantly higher levels of Vα7.2-Jα33,Vα7.2- Jα20,Vα7.2-Jα12,Cα and tumour necrosis factor (TNF),interferon (IFN)-γ and interleukin (IL)-17A transcripts,resembling a MAIT cell signature.Moreover,in AP tissues the MR1-restricted MAIT cells positive for MR1–5-OP-RU tetramer staining appeared to be of similar levels as in peripheral blood but consisted mainly of CD4^+ subset.Unlike gingival tissues,the AP microbiome was quantitatively impacted by factors like fistula and high patient age and had a prominent riboflavin-expressing bacterial feature.When merged in an integrated view,the examined immune and microbiome data in the sparse partial least squares discriminant analysis could identify bacterial relative abundances that negatively correlated with Vα7.2-Jα33,Cα,and IL-17A transcript expressions in AP,implying that MAIT cells could play a role in the local defence at the oral tissue barrier.In conclusion,we describe the presence of MAIT cells at the oral site where translocation of oral microbiota could take place.These findings have implications for understanding the immune sensing of polymicrobial-related oral diseases.
基金Supported by the Programma Ricerca Budget prestazioni Eurac 2017 of the Province of Bolzano,Italy
文摘The bacterium Helicobacter pylori(H.pylori)infects the stomachs of approximately 50%of all humans.With its universal occurrence,high infectivity and virulence properties it is considered as one of the most severe global burdens of modern humankind.It has accompanied humans for many thousands of years,and due to its high genetic variability and vertical transmission,its population genetics reflects the history of human migrations.However,especially complex demographic events such as the colonisation of Europe cannot be resolved with population genetic analysis of modern H.pylori strains alone.This is best exemplified with the reconstruction of the 5300-year-old H.pylori genome of the Iceman,a European Copper Age mummy.Our analysis provided precious insights into the ancestry and evolution of the pathogen and underlined the high complexity of ancient European population history.In this review we will provide an overview on the molecular analysis of H.pylori in mummified human remains that were done so far and we will outline methodological advancements in the field of ancient DNA research that support the reconstruction and authentication of ancient H.pylori genome sequences.
基金the Swedish Research Council(2021-01683 and 2021-06112)the Swedish Foundation for Strategic Research(SSF)(ICA16-0050)+1 种基金Svenska Lakaresallskapet(SLS-784981 and SLS-960584)the Karolinska Institute Foundation.Y.S.Z.further acknowledges support by the Brigham Research Institute.
文摘The role of the human intestinal tract in host–microbe interactions has been highlighted in recent years.Several 3-dimensional(3D)models have been developed to reproduce the physiological characteristics of the human gut and to investigate the function of the gut microbiota.One challenge for 3D models is to recapitulate the low oxygen concentrations in the intestinal lumen.Moreover,most earlier 3D culture systems used a membrane to physically separate bacteria from the intestinal epithelium,which has sometimes made the studies of bacteria adhering to or invading cells less feasible.We report the establishment of a 3D gut epithelium model and cultured it at high cell viability under an anaerobic condition.We further cocultured intestinal bacteria including both commensal and pathogen directly with epithelial cells in the established 3D model under the anaerobic condition.We subsequently compared the gene expression differences of aerobic and anaerobic conditions for cell and bacterial growth via dual RNA sequencing.Our study provides a physiologically relevant 3D gut epithelium model that mimics the anaerobic condition in the intestinal lumen and supplies a powerful system for future in-depth gut–microbe interactional investigations.
