Inflammation is often accompanied by glioblastoma cells(GBMs)and is considered a key factor for GBM growth.This feature is believed to be connected with the tryptophan pathway mainly affected by intestinal microbes si...Inflammation is often accompanied by glioblastoma cells(GBMs)and is considered a key factor for GBM growth.This feature is believed to be connected with the tryptophan pathway mainly affected by intestinal microbes since the concept of gut-brain axis(GBA)has been proposed.Here we present a microchip model co-culturing intestinal cells(Caco2),microbes(E.coli),and GBM cells(U87)to study inflammatory responses of GBM by investigating the tryptophan metabolism.E.coli after encapsulating with alginate hydrogel microparticles(AHMPs)was seeded in the microchip where Caco2 was located,forming the simulated system of intestinal physiology and avoiding excessive reproduction of microbes.Continuous flow was applied to maintain the cell viability,induce the morphogenesis,and simulate the tryptophan transportation in GBA.The morphological alterations of Caco2 and U87 were characterized by fluorescence imaging and the tryptophan metabolism,especially the tryptophan-kynurenine pathway,was analyzed by LC-MS.Above these results of molecular analysis and cell behavior,we can conclude that GBM inflammation is induced by tryptophan accumulation.This microchip-based model generally provides an alternative method for in vitro research of interactions in GBA.展开更多
The term disorders of gut-brain interaction(DGBIs)encompasses gastrointestinal disorders that globally affect more than one third of all people.The Rome IV criteria replaced the former term“functional gastrointestina...The term disorders of gut-brain interaction(DGBIs)encompasses gastrointestinal disorders that globally affect more than one third of all people.The Rome IV criteria replaced the former term“functional gastrointestinal disorders.”DGBIs can seriously challenge health and quality of life(QoL).A traditional but outdated approach differentiated“organic”vs“functional”disorders,seen by some as real vs psychiatric or undefined ones.This traditional distinction did not help patients whose health and QoL are seriously affected.DGBIs include motility disturbance;visceral hypersensitivity;altered mucosal and immune function;altered central nervous system processing,and more.Several DGBIs affect both children and adolescents.DGBIs are characterized by clusters of symptoms.Their pathophysiology relates to combinations of altered motility,visceral sensitivity,mucosal immune function,and more.Routine investigations find no structural abnormality that would easily explain the symptoms.Symptom-based criteria were developed to better understand patients where no mechanistic explanation was available for clinical practice and inclusion into clinical trials.To understand DGBIs and to find ways to treat them,these rigid mechanistic views fall short.展开更多
Typical Parkinsonian symptoms consist of bradykinesia plus rigidity and/or resting tremor. Some time later postural instability occurs. Pre-motor symptoms such as hyposmia, constipation, REM sleep behavior disorder an...Typical Parkinsonian symptoms consist of bradykinesia plus rigidity and/or resting tremor. Some time later postural instability occurs. Pre-motor symptoms such as hyposmia, constipation, REM sleep behavior disorder and depression may antecede these motor symp- toms for years. It would be ideal, if we had a biomarker which would allow to predict who with one or two of these pre-motor symptoms will develop the movement disorder Parkinson＇s disease （PD）. Thus, it is interesting to learn that biopsies of the submandibular gland or colon biopsies may be a means to predict PD, if there is a high amour of abnormally folded alpha-synuclein and phosphorylated alpha-synuclein. This would be of relevance if we would have available means to stop the propagation of abnormal alpha-synuclein which is otherwise one of the reasons of this spreading disease PD.展开更多
The aim of this study was to compare the structure of gut microbiota in Parkinson's disease(PD) patients and healthy controls;and to explore correlations between gut microbiota and PD clinical features. We analyze...The aim of this study was to compare the structure of gut microbiota in Parkinson's disease(PD) patients and healthy controls;and to explore correlations between gut microbiota and PD clinical features. We analyzed fecal bacterial composition of 24 PD patients and 14 healthy volunteers by using 16 S rRNA sequencing. There were significant differences between PD and healthy controls, as well as among different PD stages. The putative cellulose degrading bacteria from the genera Blautia(P=0.018),Faecalibacterium(P=0.048) and Ruminococcus(P=0.019) were significantly decreased in PD compared to healthy controls.The putative pathobionts from the genera Escherichia-Shigella(P=0.038), Streptococcus(P=0.01), Proteus(P=0.022), and Enterococcus(P=0.006) were significantly increased in PD subjects. Correlation analysis indicated that disease severity and PD duration negatively correlated with the putative cellulose degraders, and positively correlated with the putative pathobionts. The results suggest that structural changes of gut microbiota in PD are characterized by the decreases of putative cellulose degraders and the increases of putative pathobionts, which may potentially reduce the production of short chain fatty acids, and produce more endotoxins and neurotoxins; and these changes is potentially associated with the development of PD pathology.展开更多
基金supported by the National Key R&D Program of China(No.2021YFF0600700)the National Natural Science Foundation of China(No.22034005)+1 种基金Research Projects of Putian University(No.2024172)the Startup Fund for Advanced Talents of Putian University(No.2024046)。
文摘Inflammation is often accompanied by glioblastoma cells(GBMs)and is considered a key factor for GBM growth.This feature is believed to be connected with the tryptophan pathway mainly affected by intestinal microbes since the concept of gut-brain axis(GBA)has been proposed.Here we present a microchip model co-culturing intestinal cells(Caco2),microbes(E.coli),and GBM cells(U87)to study inflammatory responses of GBM by investigating the tryptophan metabolism.E.coli after encapsulating with alginate hydrogel microparticles(AHMPs)was seeded in the microchip where Caco2 was located,forming the simulated system of intestinal physiology and avoiding excessive reproduction of microbes.Continuous flow was applied to maintain the cell viability,induce the morphogenesis,and simulate the tryptophan transportation in GBA.The morphological alterations of Caco2 and U87 were characterized by fluorescence imaging and the tryptophan metabolism,especially the tryptophan-kynurenine pathway,was analyzed by LC-MS.Above these results of molecular analysis and cell behavior,we can conclude that GBM inflammation is induced by tryptophan accumulation.This microchip-based model generally provides an alternative method for in vitro research of interactions in GBA.
文摘The term disorders of gut-brain interaction(DGBIs)encompasses gastrointestinal disorders that globally affect more than one third of all people.The Rome IV criteria replaced the former term“functional gastrointestinal disorders.”DGBIs can seriously challenge health and quality of life(QoL).A traditional but outdated approach differentiated“organic”vs“functional”disorders,seen by some as real vs psychiatric or undefined ones.This traditional distinction did not help patients whose health and QoL are seriously affected.DGBIs include motility disturbance;visceral hypersensitivity;altered mucosal and immune function;altered central nervous system processing,and more.Several DGBIs affect both children and adolescents.DGBIs are characterized by clusters of symptoms.Their pathophysiology relates to combinations of altered motility,visceral sensitivity,mucosal immune function,and more.Routine investigations find no structural abnormality that would easily explain the symptoms.Symptom-based criteria were developed to better understand patients where no mechanistic explanation was available for clinical practice and inclusion into clinical trials.To understand DGBIs and to find ways to treat them,these rigid mechanistic views fall short.
文摘Typical Parkinsonian symptoms consist of bradykinesia plus rigidity and/or resting tremor. Some time later postural instability occurs. Pre-motor symptoms such as hyposmia, constipation, REM sleep behavior disorder and depression may antecede these motor symp- toms for years. It would be ideal, if we had a biomarker which would allow to predict who with one or two of these pre-motor symptoms will develop the movement disorder Parkinson＇s disease （PD）. Thus, it is interesting to learn that biopsies of the submandibular gland or colon biopsies may be a means to predict PD, if there is a high amour of abnormally folded alpha-synuclein and phosphorylated alpha-synuclein. This would be of relevance if we would have available means to stop the propagation of abnormal alpha-synuclein which is otherwise one of the reasons of this spreading disease PD.
基金supported by Future Life Sciences International Ltd.(NSBJ01032014,http://ffsi.jpl)
文摘The aim of this study was to compare the structure of gut microbiota in Parkinson's disease(PD) patients and healthy controls;and to explore correlations between gut microbiota and PD clinical features. We analyzed fecal bacterial composition of 24 PD patients and 14 healthy volunteers by using 16 S rRNA sequencing. There were significant differences between PD and healthy controls, as well as among different PD stages. The putative cellulose degrading bacteria from the genera Blautia(P=0.018),Faecalibacterium(P=0.048) and Ruminococcus(P=0.019) were significantly decreased in PD compared to healthy controls.The putative pathobionts from the genera Escherichia-Shigella(P=0.038), Streptococcus(P=0.01), Proteus(P=0.022), and Enterococcus(P=0.006) were significantly increased in PD subjects. Correlation analysis indicated that disease severity and PD duration negatively correlated with the putative cellulose degraders, and positively correlated with the putative pathobionts. The results suggest that structural changes of gut microbiota in PD are characterized by the decreases of putative cellulose degraders and the increases of putative pathobionts, which may potentially reduce the production of short chain fatty acids, and produce more endotoxins and neurotoxins; and these changes is potentially associated with the development of PD pathology.
