BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(I...BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.展开更多
Alzheimer's disease is a neurodegenerative disease with complex etiology.Gut microbiota influences the gutbrain axis,which may affect pathways related to the pathogenesis of Alzheimer's disease.Additionally,di...Alzheimer's disease is a neurodegenerative disease with complex etiology.Gut microbiota influences the gutbrain axis,which may affect pathways related to the pathogenesis of Alzheimer's disease.Additionally,diet and physical activity are likely to affect the pathology of Alzheimer's disease as well as the gut microbiota.This demonstrates that it may be possible to prevent or halt the progression of Alzheimer's disease by regulating the gut microbiota using diet and physical activity strategies.Therefore,the present study reviews the association between these two interventions and gut microbiota in the human body.It also summarizes how these two interventions benefit Alzheimer's disease.Furthermore,the primary limitations of these two interventions are discussed and promising strategies are proposed,which may be beneficial to further study and develop the intervening measure for the progression of Alzheimer's disease.展开更多
AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period...AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twentyeight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinkingultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits.RESULTS: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.展开更多
Helicobacter pylori (H. pylori) infection is the main pathogenic factor for upper digestive tract organic diseases. In addition to direct cytotoxic and proinflammatory effects, H. pylori infection may also induce abno...Helicobacter pylori (H. pylori) infection is the main pathogenic factor for upper digestive tract organic diseases. In addition to direct cytotoxic and proinflammatory effects, H. pylori infection may also induce abnormalities indirectly by affecting the brain-gut axis, similar to other microorganisms present in the alimentary tract. The brain-gut axis integrates the central, peripheral, enteric and autonomic nervous systems, as well as the endocrine and immunological systems, with gastrointestinal functions and environmental stimuli, including gastric and intestinal microbiota. The bidirectional relationship between H. pylori infection and the brain-gut axis influences both the contagion process and the host’s neuroendocrine-immunological reaction to it, resulting in alterations in cognitive functions, food intake and appetite, immunological response, and modification of symptom sensitivity thresholds. Furthermore, disturbances in the upper and lower digestive tract permeability, motility and secretion can occur, mainly as a form of irritable bowel syndrome. Many of these abnormalities disappear following H. pylori eradication. H. pylori may have direct neurotoxic effects that lead to alteration of the brain-gut axis through the activation of neurogenic inflammatory processes, or by microelement deficiency secondary to functional and morphological changes in the digestive tract. In digestive tissue, H. pylori can alter signaling in the brain-gut axis by mast cells, the main brain-gut axis effector, as H. pylori infection is associated with decreased mast cell infiltration in the digestive tract. Nevertheless, unequivocal data concerning the direct and immediate effect of H. pylori infection on the brain-gut axis are still lacking. Therefore, further studies evaluating the clinical importance of these host-bacteria interactions will improve our understanding of H. pylori infection pathophysiology and suggest new therapeutic approaches.展开更多
Functional gastrointestinal disorders are commonly encountered in clinical practice, and pain is their commonest presenting symptom. In addition, patients with these disorders often demonstrate a heightened sensitivit...Functional gastrointestinal disorders are commonly encountered in clinical practice, and pain is their commonest presenting symptom. In addition, patients with these disorders often demonstrate a heightened sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity that is likely to be important in their pathophysiology. Knowledge of how the brain processes sensory information from visceral structures is still in its infancy. However, our understanding has been propelled by technological imaging advances such as functional Magnetic Resonance Imaging, Positron Emission Tomography, Magnetoencephalography, and Electroencephalography (EEG). Numerous human studies have non-invasively demonstrated the complexity involved in functional pain processing, and highlighted a number of subcortical and cortical regions involved. This review will focus on the neurophysiological pathways (primary afferents, spinal and supraspinal transmission), brainimaging techniques and the influence of endogenous and psychological processes in healthy controls and patients suffering from functional gastrointestinal disorders. Special attention will be paid to the newer EEG source analysis techniques. Understanding the phenotypic differences that determine an individual's response to injurious stimuli could be the key to understanding why some patients develop pain and hyperalgesia in response to inflammation/injury while others do not. For future studies, an integrated approach is required incorporating an individual's psychological, autonomic, neuroendocrine, neurophysiological, and genetic profile to define phenotypic traits that may be at greater risk of developing sensitised states in response to gut inflammation or injury.展开更多
AIM:To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome(IBS).METHODS:A database search for relevant literature was conducted using Pub Med,Scopus...AIM:To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome(IBS).METHODS:A database search for relevant literature was conducted using Pub Med,Scopus and Embase in February 2015.Date filters were applied from the year2009 and onward,and studies were limited to those written in the English language and those performed upon human subjects.The initial search yielded 797articles,out of which 38 were pulled for full text review and 27 were included for study analysis.Investigations were reviewed to determine study design,methodology and results,and data points were placed in tabular format to facilitate analysis of study findings across disparate investigations.RESULTS:Analysis of study data resulted in the abstraction of four key themes:Neurohormonal differences,anatomic measurements of brain structure and connectivity,differences in functional responsiveness of the brain during rectal distention,and confounding/correlating patient factors.Studies in this review noted alterations of glutamate in the left hippocampus(HIPP),commonalities across IBS subjects in terms of brain oscillation patterns,cortical thickness/gray matter volume differences,and neuroanatomical regions withincreased activation in patients with IBS:Anterio cingulate cortex,mid cingulate cortex,amygdala anterior insula,posterior insula and prefrontal cortex.A striking finding among interventions was the substantia influence that patient variables(e.g.,sex,psychologica and disease related factors)had upon the identification of neuroanatomical differences in structure and con nectivity.CONCLUSION:The field of neuroimaging can provide insight into underlying physiological differences that distinguish patients with IBS from a healthy population.展开更多
Several studies have largely focused on the significant role of the nervous and immune systems in the process of tumorigenesis, including tumor growth, proliferation, apoptosis, and metastasis. The brain-gut-axis is a...Several studies have largely focused on the significant role of the nervous and immune systems in the process of tumorigenesis, including tumor growth, proliferation, apoptosis, and metastasis. The brain-gut-axis is a new paradigm in neuroscience, which describes the biochemical signaling between the gastrointestinal (GI) tract and the central nervous system. This axis may play a critical role in the tumorigenesis and development of GI cancers. Mechanistically, the bidirectional signal transmission of the brain-gut-axis is complex and remains to be elucidated. In this article, we review the current findings concerning the relationship between the brain-gut axis and GI cancer cells, focusing on the significant role of the brain-gut axis in the processes of tumor proliferation, invasion, apoptosis, autophagy, and metastasis. It appears that the brain might modulate GI cancer by two pathways: the anatomical nerve pathway and the neuroendocrine route. The simulation and inactivation of the central nervous, sympathetic, and parasympathetic nervous systems, or changes in the innervation of the GI tract might contribute to a higher incidence of GI cancers. In addition, neurotransmitters and neurotrophic factors can produce stimulatory or inhibitory effects in the progression of GI cancers. Insights into these mechanisms may lead to the discovery of potential prognostic and therapeutic targets.展开更多
Objective:To explore the therapeutic mechanism of Shenling Baizhu San (SLBZS) on functional diarrhea (FDr) by studying the brain-gut axis and related neuropeptides.Methods:Sixty male Wistar rats were randomly divided ...Objective:To explore the therapeutic mechanism of Shenling Baizhu San (SLBZS) on functional diarrhea (FDr) by studying the brain-gut axis and related neuropeptides.Methods:Sixty male Wistar rats were randomly divided into the control group,model group,SLBZS-treated group and Montmorillonite Powder-treated group (MP-treated group) (n =15/group).Rats received gavage after the establishment of functional diarrhea.An equal volume of SLBZS solution and Montmorillonite Powder (MP) solution was administered to the SLBZS-treated group and MP-treated group,respectively,and an equal volume of distilled water was administered to the control group and the model group.The chemical components and targets related to SLBZS were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID).The effective chemical components were screened based on oral bioavailability (OB) and drug like-index (DL),and their biological functions were analyzed by GlueGO.Based on this screening,the expression of Cholecystokinin (CCK) and Ghrelin in the hypothalamus of rats was detected by real-time PCR (RT-PCR) and western blotting.Results:In this study,72 effective components and 190 core targets of SLBZS were screened.SLBZS may regulate smooth muscle contraction,energy metabolism and other biological processes.The results of RT-PCR showed that in the model group,the expression of CCK mRNA (P =.001) and Ghrelin mRNA (P =.000) increased significantly.Compared with the model group,CCK mRNA (P =.007) and Ghrelin mRNA (P =.001) levels in SLBZS-treated rats were decreased significantly.The results of western blotting showed that in the model group,the protein expression of CCK (P =.001) and Ghrelin (P =.000) increased significantly.The protein levels of CCK (P =.001) and Ghrelin (P =.005) in the SLBZS-treated group were decreased significantly compared with the model group.Conclusion:SLBZS improved functional diarrhea by regulating the brain-gut axis.Changes in the expressions of brain-gut peptide,CCK and Ghrelin might explain the pathogenesis of functional diarrhea related to brain-gut peptide and gastrointestinal hormone.展开更多
Irritable bowel syndrome is one of the most common functional gastrointestinal diseases,with a global prevalence of about 12%[1].Modern studies have shown that the abnormality of brain-gut peptides is closely related ...Irritable bowel syndrome is one of the most common functional gastrointestinal diseases,with a global prevalence of about 12%[1].Modern studies have shown that the abnormality of brain-gut peptides is closely related to the occurrence of irritable bowel syndrome.This article starts with vasoactive intestinal peptide,substance P,serotonin,neuropeptide Y,corticotropin releasing factor,calcitonin gene-related peptide,cholecystokinin and other brain-gut peptides and their correlation with intestinal flora,to summarize the treatment of irritable bowel syndrome with traditional Chinese medicine in recent years.展开更多
Objective:To investigate the therapeutic effect of traditional Chinese medicine xiezhuojiedu decoction on ulcerative colitis(UC)based on zhuodu theory and its effect on serum brain-gut peptide and inflammatory factors...Objective:To investigate the therapeutic effect of traditional Chinese medicine xiezhuojiedu decoction on ulcerative colitis(UC)based on zhuodu theory and its effect on serum brain-gut peptide and inflammatory factors.Methods:110 cases of UC patients were divided into 2 groups according to the random number table method,with 55 cases in each group.The control group was treated with mesalazine,and the treatment group was given oral administration of Chinese medicine xiezhuojiedu decoction on the basis of the control group.Both groups received continuous treatment for 8 weeks.Integral of TCM syndromes,serum inflammatory factor and brain-gut peptide before and after treatment were compared between the two groups.The clinical efficiency,mucosal healing rate and endoscopic response rate of the two groups were compared.Results:After treatment,Integral of the main TCM syndromes abdominal pain,diarrhea,abdominal distention,mucous hematochezia,tenesmus of the treatment group were lower than the control group(P<0.01),the levels of serum(Tumor necrosis factor-α,(TNF-α),Interleukin(IL)-33,Substance P(SP)were lower than the control group(P<0.01),the levels of IL-10,vasoactive intestinal peptide(VIP),Somatostatin(SS)were higher than the control group(P<0.01),the clinical efficiency and mucosal healing rate were higher than control group(P<0.05),The difference was statistically significant.Conclusion:Based on the zhuodu theory,the xiezhuojiedu decoction can effectively regulate the levels of inflammatory factor and brain-gut peptide in the treatment of UC,improve the symptoms of patients,and promote the repair of intestinal mucosa.It's effective in treatment.展开更多
Acupuncture and moxibustion is an important part of traditional medicine.Acupuncture and moxibustion can affect the digestive function of human body by interfering with the interaction between the brain and the intest...Acupuncture and moxibustion is an important part of traditional medicine.Acupuncture and moxibustion can affect the digestive function of human body by interfering with the interaction between the brain and the intestines,while simultaneously having a benign adjustment effect on the mental state.In recent years,a large number of clinical studies at home and abroad have further proved the importance of acupuncture and moxibustion in the treatment of physical and mental diseases,and related mechanism studies have provided modern scientific evidence for the intervention of acupuncture and moxibustion in the brain-gut interaction from the perspectives of intestinal flora and brain functional imaging.On this basis,we integrate relevant viewpoints to provide ideas and methods for future research.展开更多
Objective:To investigate the effect of Xiaoyao San on the brain-gut axis in rats exposed to chronic immobilization stress (ClS).Methods:Rats were divided into control,model,and treatment groups.The rats belonging to t...Objective:To investigate the effect of Xiaoyao San on the brain-gut axis in rats exposed to chronic immobilization stress (ClS).Methods:Rats were divided into control,model,and treatment groups.The rats belonging to the model and treatment groups were subjected to CIS for 21 consecutive days,during which they were administered Xiaoyao San decoction [3.854 g/(kg· d)] or vehicle by gavage,and their body weight gain,food intake and water intake were monitored.The rats were subsequently subjected to the open field test (OFT) and D-XyloSe absorption test,and the expression levels of neuropeptides secreted by the hypothalamus and stomach were determined by enzyme-linked immunosorbent assay (ELISA),radioimmune analysis,or real-time fluorescence quantitative polymerase chain reaction.Gastric mucosal morphology was also assessed.Results:The model rats exhibited complex brain-gut axis abnormalities following exposure to CIS,abnormalities signified by decreases in food intake,reductions in digestive absorption,decreases in body weight,decreases in the total distances traveled and increases in the time in the central zone during the OFT,gastric mucosal lesion development and decreases in gastrointestinal hormone secretion.These changes were reversed after treatment with Xiaoyao San,which also regulated the secretion of both peripheral (serum and stomach) and central (hypothalamus) brain-gut peptides.Specifically,the levels of neuropeptide Y (NPY) and neuropeptide Y receptor Y5,which are secreted by the hypothalamus and promote digestive function,were increased in the Xiaoyao San-treated group compared with the model group.Furthermore,the levels of pro-opiomelanocortin (POMC) and its receptor,melanocortin-4 receptor (MC4R),which are secreted by the hypothalamus and inhibit digestive function,were significantly decreased in the treatment group compared with the model group.However,the levels of ghrelin (GHRL),gastrin (GAS) and motilin (MTL),which are secreted by the stomach,were significantly increased in the serum and stomach of the treatment group compared with the serum and stomach of the model group following Xiaoyao San treatment (P <.05 vs.the model group).Conclusion:Xiaoyao San attenuates CIS-induced gastrointestinal dysregulation by regulating the peptides secreted by both the hypothalamus and the gastrointestinal tract (GIT),suggesting that its effects are associated with the brain-gut axis.展开更多
Acarbose is used to control postpran-dial blood glucose in patients with type 2 diabetes and impaired glucose tolerance,since it improves insulin resistance and reduces blood lipids and cardiovascular complications.Ho...Acarbose is used to control postpran-dial blood glucose in patients with type 2 diabetes and impaired glucose tolerance,since it improves insulin resistance and reduces blood lipids and cardiovascular complications.However,in recent years,many studies have found that acarbose can mediate and regulate a variety of neurotransmitter-related diseases,although the mechanisms are not clear.Therefore,this paper analyzes the clinical effect of acarbose and its mediating effect on neurotransmitters of mental disorders through insulin,braingut axis,and calorie restriction,to provide a reference for the new clinical applications of acarbose.展开更多
文摘BACKGROUND The mucosal barrier's immune-brain interactions,pivotal for neural development and function,are increasingly recognized for their potential causal and therapeutic relevance to irritable bowel syndrome(IBS).Prior studies linking immune inflammation with IBS have been inconsistent.To further elucidate this relationship,we conducted a Mendelian randomization(MR)analysis of 731 immune cell markers to dissect the influence of various immune phenotypes on IBS.Our goal was to deepen our understanding of the disrupted brain-gut axis in IBS and to identify novel therapeutic targets.AIM To leverage publicly available data to perform MR analysis on 731 immune cell markers and explore their impact on IBS.We aimed to uncover immunophenotypic associations with IBS that could inform future drug development and therapeutic strategies.METHODS We performed a comprehensive two-sample MR analysis to evaluate the causal relationship between immune cell markers and IBS.By utilizing genetic data from public databases,we examined the causal associations between 731 immune cell markers,encompassing median fluorescence intensity,relative cell abundance,absolute cell count,and morphological parameters,with IBS susceptibility.Sensitivity analyses were conducted to validate our findings and address potential heterogeneity and pleiotropy.RESULTS Bidirectional false discovery rate correction indicated no significant influence of IBS on immunophenotypes.However,our analysis revealed a causal impact of IBS on 30 out of 731 immune phenotypes(P<0.05).Nine immune phenotypes demonstrated a protective effect against IBS[inverse variance weighting(IVW)<0.05,odd ratio(OR)<1],while 21 others were associated with an increased risk of IBS onset(IVW≥0.05,OR≥1).CONCLUSION Our findings underscore a substantial genetic correlation between immune cell phenotypes and IBS,providing valuable insights into the pathophysiology of the condition.These results pave the way for the development of more precise biomarkers and targeted therapies for IBS.Furthermore,this research enriches our comprehension of immune cell roles in IBS pathogenesis,offering a foundation for more effective,personalized treatment approaches.These advancements hold promise for improving IBS patient quality of life and reducing the disease burden on individuals and their families.
基金financially supported by National Natural Science Foundation of China(32171035)the major fund project of Ningbo Science and Technology Bureau(2019B10034)+4 种基金Opened-end Fund of Key Laboratory(KFJJ-202101,ZPKLP202202)Public Project of Ningbo(202002N3167)Project of Yinzhou(2022AS025)Ningbo Rehabilitation Hospital(2022KY02)sponsored by a K.C.Wong Magna Fund in Ningbo University。
文摘Alzheimer's disease is a neurodegenerative disease with complex etiology.Gut microbiota influences the gutbrain axis,which may affect pathways related to the pathogenesis of Alzheimer's disease.Additionally,diet and physical activity are likely to affect the pathology of Alzheimer's disease as well as the gut microbiota.This demonstrates that it may be possible to prevent or halt the progression of Alzheimer's disease by regulating the gut microbiota using diet and physical activity strategies.Therefore,the present study reviews the association between these two interventions and gut microbiota in the human body.It also summarizes how these two interventions benefit Alzheimer's disease.Furthermore,the primary limitations of these two interventions are discussed and promising strategies are proposed,which may be beneficial to further study and develop the intervening measure for the progression of Alzheimer's disease.
文摘AIM: To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. METHODS: This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twentyeight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinkingultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits.RESULTS: AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. CONCLUSION: Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.
文摘Helicobacter pylori (H. pylori) infection is the main pathogenic factor for upper digestive tract organic diseases. In addition to direct cytotoxic and proinflammatory effects, H. pylori infection may also induce abnormalities indirectly by affecting the brain-gut axis, similar to other microorganisms present in the alimentary tract. The brain-gut axis integrates the central, peripheral, enteric and autonomic nervous systems, as well as the endocrine and immunological systems, with gastrointestinal functions and environmental stimuli, including gastric and intestinal microbiota. The bidirectional relationship between H. pylori infection and the brain-gut axis influences both the contagion process and the host’s neuroendocrine-immunological reaction to it, resulting in alterations in cognitive functions, food intake and appetite, immunological response, and modification of symptom sensitivity thresholds. Furthermore, disturbances in the upper and lower digestive tract permeability, motility and secretion can occur, mainly as a form of irritable bowel syndrome. Many of these abnormalities disappear following H. pylori eradication. H. pylori may have direct neurotoxic effects that lead to alteration of the brain-gut axis through the activation of neurogenic inflammatory processes, or by microelement deficiency secondary to functional and morphological changes in the digestive tract. In digestive tissue, H. pylori can alter signaling in the brain-gut axis by mast cells, the main brain-gut axis effector, as H. pylori infection is associated with decreased mast cell infiltration in the digestive tract. Nevertheless, unequivocal data concerning the direct and immediate effect of H. pylori infection on the brain-gut axis are still lacking. Therefore, further studies evaluating the clinical importance of these host-bacteria interactions will improve our understanding of H. pylori infection pathophysiology and suggest new therapeutic approaches.
基金Supported by A Medical Research Council Career Establi-shment Award and the Rosetrees Trust
文摘Functional gastrointestinal disorders are commonly encountered in clinical practice, and pain is their commonest presenting symptom. In addition, patients with these disorders often demonstrate a heightened sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity that is likely to be important in their pathophysiology. Knowledge of how the brain processes sensory information from visceral structures is still in its infancy. However, our understanding has been propelled by technological imaging advances such as functional Magnetic Resonance Imaging, Positron Emission Tomography, Magnetoencephalography, and Electroencephalography (EEG). Numerous human studies have non-invasively demonstrated the complexity involved in functional pain processing, and highlighted a number of subcortical and cortical regions involved. This review will focus on the neurophysiological pathways (primary afferents, spinal and supraspinal transmission), brainimaging techniques and the influence of endogenous and psychological processes in healthy controls and patients suffering from functional gastrointestinal disorders. Special attention will be paid to the newer EEG source analysis techniques. Understanding the phenotypic differences that determine an individual's response to injurious stimuli could be the key to understanding why some patients develop pain and hyperalgesia in response to inflammation/injury while others do not. For future studies, an integrated approach is required incorporating an individual's psychological, autonomic, neuroendocrine, neurophysiological, and genetic profile to define phenotypic traits that may be at greater risk of developing sensitised states in response to gut inflammation or injury.
基金Supported by Division of Intramural ResearchNational Institute of Nursing Research to W.A.H.No.1ZIANR000018-01-05
文摘AIM:To summarize and synthesize current literature on neuroimaging the brain-gut axis in patients with irritable bowel syndrome(IBS).METHODS:A database search for relevant literature was conducted using Pub Med,Scopus and Embase in February 2015.Date filters were applied from the year2009 and onward,and studies were limited to those written in the English language and those performed upon human subjects.The initial search yielded 797articles,out of which 38 were pulled for full text review and 27 were included for study analysis.Investigations were reviewed to determine study design,methodology and results,and data points were placed in tabular format to facilitate analysis of study findings across disparate investigations.RESULTS:Analysis of study data resulted in the abstraction of four key themes:Neurohormonal differences,anatomic measurements of brain structure and connectivity,differences in functional responsiveness of the brain during rectal distention,and confounding/correlating patient factors.Studies in this review noted alterations of glutamate in the left hippocampus(HIPP),commonalities across IBS subjects in terms of brain oscillation patterns,cortical thickness/gray matter volume differences,and neuroanatomical regions withincreased activation in patients with IBS:Anterio cingulate cortex,mid cingulate cortex,amygdala anterior insula,posterior insula and prefrontal cortex.A striking finding among interventions was the substantia influence that patient variables(e.g.,sex,psychologica and disease related factors)had upon the identification of neuroanatomical differences in structure and con nectivity.CONCLUSION:The field of neuroimaging can provide insight into underlying physiological differences that distinguish patients with IBS from a healthy population.
文摘Several studies have largely focused on the significant role of the nervous and immune systems in the process of tumorigenesis, including tumor growth, proliferation, apoptosis, and metastasis. The brain-gut-axis is a new paradigm in neuroscience, which describes the biochemical signaling between the gastrointestinal (GI) tract and the central nervous system. This axis may play a critical role in the tumorigenesis and development of GI cancers. Mechanistically, the bidirectional signal transmission of the brain-gut-axis is complex and remains to be elucidated. In this article, we review the current findings concerning the relationship between the brain-gut axis and GI cancer cells, focusing on the significant role of the brain-gut axis in the processes of tumor proliferation, invasion, apoptosis, autophagy, and metastasis. It appears that the brain might modulate GI cancer by two pathways: the anatomical nerve pathway and the neuroendocrine route. The simulation and inactivation of the central nervous, sympathetic, and parasympathetic nervous systems, or changes in the innervation of the GI tract might contribute to a higher incidence of GI cancers. In addition, neurotransmitters and neurotrophic factors can produce stimulatory or inhibitory effects in the progression of GI cancers. Insights into these mechanisms may lead to the discovery of potential prognostic and therapeutic targets.
文摘Objective:To explore the therapeutic mechanism of Shenling Baizhu San (SLBZS) on functional diarrhea (FDr) by studying the brain-gut axis and related neuropeptides.Methods:Sixty male Wistar rats were randomly divided into the control group,model group,SLBZS-treated group and Montmorillonite Powder-treated group (MP-treated group) (n =15/group).Rats received gavage after the establishment of functional diarrhea.An equal volume of SLBZS solution and Montmorillonite Powder (MP) solution was administered to the SLBZS-treated group and MP-treated group,respectively,and an equal volume of distilled water was administered to the control group and the model group.The chemical components and targets related to SLBZS were identified from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID).The effective chemical components were screened based on oral bioavailability (OB) and drug like-index (DL),and their biological functions were analyzed by GlueGO.Based on this screening,the expression of Cholecystokinin (CCK) and Ghrelin in the hypothalamus of rats was detected by real-time PCR (RT-PCR) and western blotting.Results:In this study,72 effective components and 190 core targets of SLBZS were screened.SLBZS may regulate smooth muscle contraction,energy metabolism and other biological processes.The results of RT-PCR showed that in the model group,the expression of CCK mRNA (P =.001) and Ghrelin mRNA (P =.000) increased significantly.Compared with the model group,CCK mRNA (P =.007) and Ghrelin mRNA (P =.001) levels in SLBZS-treated rats were decreased significantly.The results of western blotting showed that in the model group,the protein expression of CCK (P =.001) and Ghrelin (P =.000) increased significantly.The protein levels of CCK (P =.001) and Ghrelin (P =.005) in the SLBZS-treated group were decreased significantly compared with the model group.Conclusion:SLBZS improved functional diarrhea by regulating the brain-gut axis.Changes in the expressions of brain-gut peptide,CCK and Ghrelin might explain the pathogenesis of functional diarrhea related to brain-gut peptide and gastrointestinal hormone.
基金National Training Program for Backbone Talents of Clinical Characteristic Technology Inheritance of Traditional Chinese Medicine[Chinese Medicine Renjiaofa(2019)No.36]。
文摘Irritable bowel syndrome is one of the most common functional gastrointestinal diseases,with a global prevalence of about 12%[1].Modern studies have shown that the abnormality of brain-gut peptides is closely related to the occurrence of irritable bowel syndrome.This article starts with vasoactive intestinal peptide,substance P,serotonin,neuropeptide Y,corticotropin releasing factor,calcitonin gene-related peptide,cholecystokinin and other brain-gut peptides and their correlation with intestinal flora,to summarize the treatment of irritable bowel syndrome with traditional Chinese medicine in recent years.
基金Doctor’s initial funding project in Liaoning province(No.20111093).
文摘Objective:To investigate the therapeutic effect of traditional Chinese medicine xiezhuojiedu decoction on ulcerative colitis(UC)based on zhuodu theory and its effect on serum brain-gut peptide and inflammatory factors.Methods:110 cases of UC patients were divided into 2 groups according to the random number table method,with 55 cases in each group.The control group was treated with mesalazine,and the treatment group was given oral administration of Chinese medicine xiezhuojiedu decoction on the basis of the control group.Both groups received continuous treatment for 8 weeks.Integral of TCM syndromes,serum inflammatory factor and brain-gut peptide before and after treatment were compared between the two groups.The clinical efficiency,mucosal healing rate and endoscopic response rate of the two groups were compared.Results:After treatment,Integral of the main TCM syndromes abdominal pain,diarrhea,abdominal distention,mucous hematochezia,tenesmus of the treatment group were lower than the control group(P<0.01),the levels of serum(Tumor necrosis factor-α,(TNF-α),Interleukin(IL)-33,Substance P(SP)were lower than the control group(P<0.01),the levels of IL-10,vasoactive intestinal peptide(VIP),Somatostatin(SS)were higher than the control group(P<0.01),the clinical efficiency and mucosal healing rate were higher than control group(P<0.05),The difference was statistically significant.Conclusion:Based on the zhuodu theory,the xiezhuojiedu decoction can effectively regulate the levels of inflammatory factor and brain-gut peptide in the treatment of UC,improve the symptoms of patients,and promote the repair of intestinal mucosa.It's effective in treatment.
基金the Postgraduate Research Innovation Program of Jiangsu Province(grant number KYCX20_1472)the Leading Talents of Traditional Chinese Medicine in Jiangsu(grant number SLJ0225)the Research Project of Nanjing University of Chinese Medicine(grant number XT202001).
文摘Acupuncture and moxibustion is an important part of traditional medicine.Acupuncture and moxibustion can affect the digestive function of human body by interfering with the interaction between the brain and the intestines,while simultaneously having a benign adjustment effect on the mental state.In recent years,a large number of clinical studies at home and abroad have further proved the importance of acupuncture and moxibustion in the treatment of physical and mental diseases,and related mechanism studies have provided modern scientific evidence for the intervention of acupuncture and moxibustion in the brain-gut interaction from the perspectives of intestinal flora and brain functional imaging.On this basis,we integrate relevant viewpoints to provide ideas and methods for future research.
基金This paper was supported by the National Natural Science Foundation of China(.81473597 and 81630104)the China National Funds for Distinguished Young Scientists(30825046)the Beijing Municipal Natural Science Foundation(7152093).
文摘Objective:To investigate the effect of Xiaoyao San on the brain-gut axis in rats exposed to chronic immobilization stress (ClS).Methods:Rats were divided into control,model,and treatment groups.The rats belonging to the model and treatment groups were subjected to CIS for 21 consecutive days,during which they were administered Xiaoyao San decoction [3.854 g/(kg· d)] or vehicle by gavage,and their body weight gain,food intake and water intake were monitored.The rats were subsequently subjected to the open field test (OFT) and D-XyloSe absorption test,and the expression levels of neuropeptides secreted by the hypothalamus and stomach were determined by enzyme-linked immunosorbent assay (ELISA),radioimmune analysis,or real-time fluorescence quantitative polymerase chain reaction.Gastric mucosal morphology was also assessed.Results:The model rats exhibited complex brain-gut axis abnormalities following exposure to CIS,abnormalities signified by decreases in food intake,reductions in digestive absorption,decreases in body weight,decreases in the total distances traveled and increases in the time in the central zone during the OFT,gastric mucosal lesion development and decreases in gastrointestinal hormone secretion.These changes were reversed after treatment with Xiaoyao San,which also regulated the secretion of both peripheral (serum and stomach) and central (hypothalamus) brain-gut peptides.Specifically,the levels of neuropeptide Y (NPY) and neuropeptide Y receptor Y5,which are secreted by the hypothalamus and promote digestive function,were increased in the Xiaoyao San-treated group compared with the model group.Furthermore,the levels of pro-opiomelanocortin (POMC) and its receptor,melanocortin-4 receptor (MC4R),which are secreted by the hypothalamus and inhibit digestive function,were significantly decreased in the treatment group compared with the model group.However,the levels of ghrelin (GHRL),gastrin (GAS) and motilin (MTL),which are secreted by the stomach,were significantly increased in the serum and stomach of the treatment group compared with the serum and stomach of the model group following Xiaoyao San treatment (P <.05 vs.the model group).Conclusion:Xiaoyao San attenuates CIS-induced gastrointestinal dysregulation by regulating the peptides secreted by both the hypothalamus and the gastrointestinal tract (GIT),suggesting that its effects are associated with the brain-gut axis.
文摘Acarbose is used to control postpran-dial blood glucose in patients with type 2 diabetes and impaired glucose tolerance,since it improves insulin resistance and reduces blood lipids and cardiovascular complications.However,in recent years,many studies have found that acarbose can mediate and regulate a variety of neurotransmitter-related diseases,although the mechanisms are not clear.Therefore,this paper analyzes the clinical effect of acarbose and its mediating effect on neurotransmitters of mental disorders through insulin,braingut axis,and calorie restriction,to provide a reference for the new clinical applications of acarbose.