This study explored the therapeutic effect of trimebutine maleate dispersible tablets combined with berberine on PI-IBS rats with liver depression and spleen deficiency.Fifty male rats were divided into five groups:no...This study explored the therapeutic effect of trimebutine maleate dispersible tablets combined with berberine on PI-IBS rats with liver depression and spleen deficiency.Fifty male rats were divided into five groups:normal,model,berberine(XB),trimebutine(QM),and combination(XB+QM).The PI-IBS model was established using maternal separation,TNBS perfusion,and chronic restraint.After 20 days of drug intervention,DAI,CMDI,TDI,AWR scores,histopathology,and expression levels of c-Fos,VIP,NOS,and CHAT in the hippocampus and colon were assessed.The model group showed significant gut and brain changes,while the combination group(XB+QM)improved fecal characteristics,reduced inflammation,regulated brain-gut peptide expression,and alleviated visceral hypersensitivity and colon tissue damage(P<0.05).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
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
Parkinson's disease(PD) is characterized by alphasynucleinopathy that affects all levels of the braingut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that th...Parkinson's disease(PD) is characterized by alphasynucleinopathy that affects all levels of the braingut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological,neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding.Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gutmicrobiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.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
OBJECTIVE: To evaluate the effect of Weichang'an pill( 胃肠安丸, WCAP) on functional dyspepsia(FD) and explore its regulation of brain-gut peptides(BGPs) and gut microbiota balance as a potential treatment mechani...OBJECTIVE: To evaluate the effect of Weichang'an pill( 胃肠安丸, WCAP) on functional dyspepsia(FD) and explore its regulation of brain-gut peptides(BGPs) and gut microbiota balance as a potential treatment mechanism. METHODS: The "0 ℃ saline gavage + irregular feeding and tail clamp" method was used to establish the FD rat model, excluding the normal group. The successfully established FD rat models were randomly divided into the model group and the WCAP1(WC1), WCAP2(WC2), WCAP3(WC3), WCAP4(WC4), WCAP5(WC5), and Domperidone(Dom) groups(n = 10 per group). The unhandled rats were designated as the control group. The gastrointestinal motility of the rats was evaluated using the charcoal propulsion test. Histopathology was assessed by hematoxylin and eosin(HE) staining. The enzyme-linked immunosorbnent assay method was used to detect the levels of motilin(MTL), gastrin(GAS), vasoactive intestinal peptide(VIP), and somatostatin(SS) in the serum from each group. In addition, the gut microbiota composition of fecal samples was analyzed using 16S r RNA sequencing. RESULTS: Rat models were successfully established according to data from rat state, gastrointestinal motility assessments, and HE staining. WCAP improved FD symptoms by accelerating the gastric emptying and small intestinal transit of FD rats. Mechanistically, WCAP increased the levels of GAS and MTL and reduced the levels of VIP and SS. Moreover, WCAP treatment restored the total relative abundance of Firmicutes and Bacteroidetes, increased the species richness of the gut flora, and modulated the changes in the composition and function of the gut microbiota. CONCLUSION: WCAP can effectively promote the recovery of gastrointestinal motility disorders in FD rats. The mechanism may be related to regulating the secretion of BGPs and the composition of the gut microbiota.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
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
Cleaning away Heat and Dampness is one of the general methods in treating the syndrome of the Spleen and Stomach’s damp heat in Febrile Diseases,and its efficacy of invigorating the spleen regulating the stomach is i...Cleaning away Heat and Dampness is one of the general methods in treating the syndrome of the Spleen and Stomach’s damp heat in Febrile Diseases,and its efficacy of invigorating the spleen regulating the stomach is involved in regulation of gastrointestinal motility.Many factors and systems act as the regulation,including Brain-gut peptide,which quantitative change in the gastrointestinal tissues and plasma can reflex the functions of gastrointestinal motility.So carrying on an investigation into the relation between brain-gut peptide and its receptors and gastrointestinal dyskinesia in the syndrome of damp heat in the spleen and stomach has its relevant to the explanation of the mechanism of cleaning away Heat and Dampness.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
The brain-gut axis is a bidirectional signal transduction system between the gastrointestinal tract and the central nervous system that integrates neural,endocrine,and immune functions.In recent years,the role of the ...The brain-gut axis is a bidirectional signal transduction system between the gastrointestinal tract and the central nervous system that integrates neural,endocrine,and immune functions.In recent years,the role of the intestinal flora in regulating neural function and affecting the progression of different neurological diseases has received increasing attention.Akkermansia muciniphila is a mucin-degrading bacterium of the intestinal flora present in the intestinal mucus layer that can regulate host immunity,the intestinal barrier and neuroimmune homeostasis.In recent years,a growing body of literature has suggested that Akkermansia muciniphila may play beneficial roles in nerve injury and regeneration by regulating brain-gut axis signalling.This review comprehensively summarizes the latest research results on the role of Akkermansia muciniphila in neurological diseases such as spinal cord injury,multiple sclerosis,Parkinson’s disease,and Alzheimer’s disease.The mechanisms by which Akkermansia muciniphila regulates inflammatory cytokines,neurotransmitters,and short-chain fatty acids are also highlighted.Various Akkermansia muciniphila-based interventions,such as those involving outer membrane proteins,extracellular vesicles,and pasteurized Akkermansia muciniphila,are discussed,and their therapeutic potential in restoring intestinal homeostasis,alleviating neuroinflammation,and supporting neuronal repair is explored.Although promising results from animal models have been reported,significant challenges remain in translating these findings into clinical practice and therapeutic applications.The differences in Akkermansia muciniphila colonization efficiency,host responses,and intervention strategies in different disease states limit the results of these studies.In addition,Akkermansia muciniphila may exhibit different mechanisms of action in acute and chronic neurodegenerative diseases,and thus more targeted mechanistic studies are needed.Despite these limitations,Akkermansia muciniphila represents a novel and potent pathway for the modulation of the brain-gut axis to support neural repair and functional recovery.By enhancing intestinal barrier integrity and regulating neuroimmunity,Akkermansia muciniphila has broad prospects as a microbial candidate for the treatment of central nervous system diseases.Future research should focus on optimizing the administration method and clinical trials to verify its efficacy,ultimately providing new treatment options in the field of neural regeneration and microbial therapy.展开更多
酒精使用障碍(alcohol use disorder,AUD)是一种复杂的慢性复发性脑部疾病,对个体健康和公共卫生构成重大影响。痛觉过敏是导致AUD治疗失败的关键因素。现有药物不能有效缓解AUD患者的疼痛,因而亟需研发新的干预措施。本文系统综述了AU...酒精使用障碍(alcohol use disorder,AUD)是一种复杂的慢性复发性脑部疾病,对个体健康和公共卫生构成重大影响。痛觉过敏是导致AUD治疗失败的关键因素。现有药物不能有效缓解AUD患者的疼痛,因而亟需研发新的干预措施。本文系统综述了AUD导致痛觉过敏的多系统神经生物学机制,从分子到环路,再从中枢到外周,揭示了神经递质失衡[如谷氨酸能兴奋增强/γ-氨基丁酸(γ-aminobutyric acid,GABA)能抑制]、神经胶质细胞介导的神经炎症等经典通路,并深入分析了表观遗传调控(DNA甲基化、组蛋白修饰和microRNA对关键基因的表达调控)和肠-脑轴(肠道菌群通过代谢物影响中枢神经系统)等新型机制,同时强调了性激素介导的性别差异性。基于这些见解,本文提出靶向神经环路、表观遗传修饰酶、肠道菌群等新型干预策略,为临床治疗AUD引起的痛觉过敏提供新视角,这对降低复饮率、改善患者预后具有重要意义。展开更多
基金Science and Technology Fund Project of Guizhou Provincial Health Commission(Project No.:gawkj2021-225).
文摘This study explored the therapeutic effect of trimebutine maleate dispersible tablets combined with berberine on PI-IBS rats with liver depression and spleen deficiency.Fifty male rats were divided into five groups:normal,model,berberine(XB),trimebutine(QM),and combination(XB+QM).The PI-IBS model was established using maternal separation,TNBS perfusion,and chronic restraint.After 20 days of drug intervention,DAI,CMDI,TDI,AWR scores,histopathology,and expression levels of c-Fos,VIP,NOS,and CHAT in the hippocampus and colon were assessed.The model group showed significant gut and brain changes,while the combination group(XB+QM)improved fecal characteristics,reduced inflammation,regulated brain-gut peptide expression,and alleviated visceral hypersensitivity and colon tissue damage(P<0.05).
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.
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.
文摘Parkinson's disease(PD) is characterized by alphasynucleinopathy that affects all levels of the braingut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological,neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding.Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gutmicrobiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.
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.
基金Horizontal Development Foundation of Beijing University of Chinese Medicine:Research and development of Weicang’an pill in the treatment of functional dyspepsia (2018110031010092)。
文摘OBJECTIVE: To evaluate the effect of Weichang'an pill( 胃肠安丸, WCAP) on functional dyspepsia(FD) and explore its regulation of brain-gut peptides(BGPs) and gut microbiota balance as a potential treatment mechanism. METHODS: The "0 ℃ saline gavage + irregular feeding and tail clamp" method was used to establish the FD rat model, excluding the normal group. The successfully established FD rat models were randomly divided into the model group and the WCAP1(WC1), WCAP2(WC2), WCAP3(WC3), WCAP4(WC4), WCAP5(WC5), and Domperidone(Dom) groups(n = 10 per group). The unhandled rats were designated as the control group. The gastrointestinal motility of the rats was evaluated using the charcoal propulsion test. Histopathology was assessed by hematoxylin and eosin(HE) staining. The enzyme-linked immunosorbnent assay method was used to detect the levels of motilin(MTL), gastrin(GAS), vasoactive intestinal peptide(VIP), and somatostatin(SS) in the serum from each group. In addition, the gut microbiota composition of fecal samples was analyzed using 16S r RNA sequencing. RESULTS: Rat models were successfully established according to data from rat state, gastrointestinal motility assessments, and HE staining. WCAP improved FD symptoms by accelerating the gastric emptying and small intestinal transit of FD rats. Mechanistically, WCAP increased the levels of GAS and MTL and reduced the levels of VIP and SS. Moreover, WCAP treatment restored the total relative abundance of Firmicutes and Bacteroidetes, increased the species richness of the gut flora, and modulated the changes in the composition and function of the gut microbiota. CONCLUSION: WCAP can effectively promote the recovery of gastrointestinal motility disorders in FD rats. The mechanism may be related to regulating the secretion of BGPs and the composition of the gut microbiota.
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Cleaning away Heat and Dampness is one of the general methods in treating the syndrome of the Spleen and Stomach’s damp heat in Febrile Diseases,and its efficacy of invigorating the spleen regulating the stomach is involved in regulation of gastrointestinal motility.Many factors and systems act as the regulation,including Brain-gut peptide,which quantitative change in the gastrointestinal tissues and plasma can reflex the functions of gastrointestinal motility.So carrying on an investigation into the relation between brain-gut peptide and its receptors and gastrointestinal dyskinesia in the syndrome of damp heat in the spleen and stomach has its relevant to the explanation of the mechanism of cleaning away Heat and Dampness.
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supported by the Anhui Province Education Commission Foundation,No.2023AH040262(to JQ)the National Natural Science Foundation of China,No.82372540(to KZ)+2 种基金Anhui Province Health Commission Project,No.AHWJ2022b054(to JQ)Key Project of Wannan Medical College,No.WK2022ZF20(to JQ)Talent Research Fund Program of The First Affiliated Hospital of Wannan Medical College,No.YR20220215(to JQ).
文摘The brain-gut axis is a bidirectional signal transduction system between the gastrointestinal tract and the central nervous system that integrates neural,endocrine,and immune functions.In recent years,the role of the intestinal flora in regulating neural function and affecting the progression of different neurological diseases has received increasing attention.Akkermansia muciniphila is a mucin-degrading bacterium of the intestinal flora present in the intestinal mucus layer that can regulate host immunity,the intestinal barrier and neuroimmune homeostasis.In recent years,a growing body of literature has suggested that Akkermansia muciniphila may play beneficial roles in nerve injury and regeneration by regulating brain-gut axis signalling.This review comprehensively summarizes the latest research results on the role of Akkermansia muciniphila in neurological diseases such as spinal cord injury,multiple sclerosis,Parkinson’s disease,and Alzheimer’s disease.The mechanisms by which Akkermansia muciniphila regulates inflammatory cytokines,neurotransmitters,and short-chain fatty acids are also highlighted.Various Akkermansia muciniphila-based interventions,such as those involving outer membrane proteins,extracellular vesicles,and pasteurized Akkermansia muciniphila,are discussed,and their therapeutic potential in restoring intestinal homeostasis,alleviating neuroinflammation,and supporting neuronal repair is explored.Although promising results from animal models have been reported,significant challenges remain in translating these findings into clinical practice and therapeutic applications.The differences in Akkermansia muciniphila colonization efficiency,host responses,and intervention strategies in different disease states limit the results of these studies.In addition,Akkermansia muciniphila may exhibit different mechanisms of action in acute and chronic neurodegenerative diseases,and thus more targeted mechanistic studies are needed.Despite these limitations,Akkermansia muciniphila represents a novel and potent pathway for the modulation of the brain-gut axis to support neural repair and functional recovery.By enhancing intestinal barrier integrity and regulating neuroimmunity,Akkermansia muciniphila has broad prospects as a microbial candidate for the treatment of central nervous system diseases.Future research should focus on optimizing the administration method and clinical trials to verify its efficacy,ultimately providing new treatment options in the field of neural regeneration and microbial therapy.
基金supported by the National Natural Science Foundation of China(No.82271256 and 32200817)General Program from Nantong Commission of Health(No.MS2024049)Guided Research Program of Nantong Municipal Bureau of Science and Technology(No.JCZ2023023)。
文摘酒精使用障碍(alcohol use disorder,AUD)是一种复杂的慢性复发性脑部疾病,对个体健康和公共卫生构成重大影响。痛觉过敏是导致AUD治疗失败的关键因素。现有药物不能有效缓解AUD患者的疼痛,因而亟需研发新的干预措施。本文系统综述了AUD导致痛觉过敏的多系统神经生物学机制,从分子到环路,再从中枢到外周,揭示了神经递质失衡[如谷氨酸能兴奋增强/γ-氨基丁酸(γ-aminobutyric acid,GABA)能抑制]、神经胶质细胞介导的神经炎症等经典通路,并深入分析了表观遗传调控(DNA甲基化、组蛋白修饰和microRNA对关键基因的表达调控)和肠-脑轴(肠道菌群通过代谢物影响中枢神经系统)等新型机制,同时强调了性激素介导的性别差异性。基于这些见解,本文提出靶向神经环路、表观遗传修饰酶、肠道菌群等新型干预策略,为临床治疗AUD引起的痛觉过敏提供新视角,这对降低复饮率、改善患者预后具有重要意义。
