Application progress of Chinese medicine in the treatment of irritable bowel syndrome based on the brain-gut axis theory

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.

Effect of amitriptyline on gastrointestinal function and brain-gut peptides: A double-blind trial

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.

Brain-gut axis in the pathogenesis of Helicobacter pylori infection

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&#x02019;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.

Brain-gut-microbiota axis in Parkinson's disease

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.

New technologies to investigate the brain-gut axis

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.

Neuroimaging the brain-gut axis in patients with irritable bowel syndrome

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.

Role of the brain-gut axis in gastrointestinal cancer

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.

Study on the regulation of brain-gut peptide by Shenling Baizhu San in functional diarrhea rats

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.

The Role and Significance of Brain-gut Peptide and Its Receptor's Expression in the Mechanism's Explanation of Cleaning Away Heat and Dampness

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.

Therapeutic effect of zhuodu theory on ulcerative colitis and its effect on brain-gut peptide in serum and inflammatory factor

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.

Effect of Xiaoyao San on the brain-gut axis in rats after chronic immobilization stress

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.

Clinical Application and Mechanism of Acupuncture in the Brain-Gut Interaction

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.

Weichang’an pill(胃肠安丸)alleviates functional dyspepsia through modulating brain-gut peptides and gut microbiota

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.

基于“微生物-肠-脑轴”探讨补肾通腑方对APP/PS1小鼠肠道菌群及LPS/TLR4/NF-κB通路的影响

目的探讨补肾通腑方调控肠道菌群,改善阿尔茨海默病(Alzheimer’s disease,AD)模型小鼠学习记忆能力的作用机制。方法以APP/PS1小鼠为研究对象,给予补肾通腑方治疗8周,采用Morris水迷宫法观察小鼠空间学习记忆能力变化;16S rDNA检测小鼠肠道菌群丰度、多样性变化;HE染色观察海马病理形态学变化;免疫荧光检测海马区小胶质细胞活化情况;Western blot检测TLR4、NF-κB、IL-6等炎症因子表达。结果与模型组相比,补肾通腑方可以缩短AD模型小鼠逃避潜伏期、游泳路径,增加跨越平台次数(P<0.05),提升肠道菌群多样性,调节肠道菌群丰度,促进海马神经元细胞损伤修复,降低iNOS/Iba1共表达,提高Arg1/Iba1共表达(P<0.01),促进小胶质细胞从M1型向M2型转化,下调TLR4、NF-κB、IL-6等促炎因子的表达。结论补肾通腑方改善AD模型小鼠学习记忆能力的作用机制可能与调节肠道菌群介导的LPS/TLR4/NF-κB通路,从而抑制促炎型小胶质细胞活化、减轻中枢神经系统炎症、改善海马区神经元细胞损伤有关。

Efficacy and effect on related brain-gut peptides of acupoint sticking therapy for functional dyspepsia

Objective:To observe the efficacy of acupoint sticking with Jianpi Tongjing Zhitong ointmerrt in the treatment of functional dyspepsia due to liver-qi stagnation and spleen deficiency and its effect on serum 5-hydroxytryptamine(5-HT)and ghrelin con tents.Methods:One hun dred patients with functi onal dyspepsia due to liver-qi stag nation and spleen deficiency were divided into a treatment group and a control group by the random number table method,with 50 cases in each group.The treatment group received acupoint sticking with Jianpi Tongjing Zhitong ointment and the control group was treated with mosapride citrate orally.Patients were treated for 4 weeks as a course.The therapeutic efficacy was compared after one-course treatment and the differences in gastric emptying rate,and serum 5-HT and ghrelin contents between groups were compared before and after treatment.Results:The total effective rate was 79.6%in the control group and 89.4%in the treatment group,showing significantly differe nt between groups(P<0.05).After treatme nt,the gastric empt ying rate and serum ghreli n con tent of the two groups in creased significantly,and the serum 5-HT content decreased significantly,the intra-group differe nces were significant(all P<0.01).After treatment,the gastric emptying rate and serum ghrelin content were significantly higher in the treatment group than those in the control group,while the serum 5-HT was significant lower in the treatment group,the inter-group differences were significant(all P<0.05).A negative correlation(r=-0.59)was observed between serum 5-HT content and gastric emptying rate,and a positive correlation(r=0.64)was observed between serum ghrelin content and gastric emptying rate,showing statistical significance(all P<0.01).Conclusion:Acupoint sticking with Jianpi Tongjing Zhitong ointment has a remarkable ciinical efficacy in treating patie nts with functional dyspepsia due to liver-qi stagnation and spleen deficiency and is able to in fluence the secretion of serum 5-HT and ghrelin-1 mproving the gastrointestinal motility through the regulation of related brain-gut peptides is suggested as an underlying mechanism for this therapy.

基于脑肠轴理论探讨捏脊对儿童生长发育的影响

脑肠轴理论是现代医学提出的关于大脑与肠道之间相互作用的概念。而祖国传统医学中的捏脊手法是通过刺激“入络脑”的“阳脉之海”——督脉,以及其两旁的肌肉激发人体各脏腑、系统功能,从而对人体尤其是生长发育期儿童的脏腑调节、生长发育、脑发育等起到正向作用。本文基于脑肠轴理论,探讨肠道如何通过神经内分泌、免疫、代谢物通路影响大脑功能的机制,联系捏脊手法作用于背部特定经络区域,从而激活神经内分泌系统、调控肠菌群、调节免疫系统等的现代医学作用机制,以及通过刺激督脉维系脏腑之元阳、汇一身之阳入督荣脑以达到脑肠同调的中医作用机制,探讨捏脊疗法在儿童生长发育中对其调节脏腑,促进大脑发育的影响。

脑肠同调论针刺治疗急性脑梗死血清代谢组学研究

目的 分析脑肠同调论针刺治疗急性脑梗死的血清代谢组学的影响。方法 纳入2018年3月—2022年12月医院收治的急性脑梗死患者126例作为研究对象,随机数字表法分为两组,对照组63例采用常规疗法,观察组63例在此基础上采用脑肠同调论针刺治疗,对比两组治疗效果、神经功能,炎症因子水平以及对血清代谢组学的影响。结果 观察组总有效率为96.83%(61/63),远高于对照组的80.96%(57/63),神经功能缺损评分(NIHSS)评分低于对照组(P<0.05);治疗后观察组白介素-17(Interleukin-17,IL-17)、超敏C反应蛋白(hypersensitive C-reactive protein, hs-CRP)、血浆氧化三甲胺(trimethylamine oxide, TMAO)水平均低于对照组(P<0.05);治疗后观察组苯丙氨酸、溶血卵磷脂、焦谷氨酸水平低于对照组(P<0.05)。结论 脑肠同调论针刺治疗急性脑梗死效果明确,可减轻患者炎症反应,调节其肠道菌群代谢产物水平及氨基酸、磷脂代谢障碍等,使紊乱的代谢趋于正常,以达促进神经功能恢复,改善患者预后的目的,有较高应用价值。

基于肠道微生物菌群探讨针灸治疗肠易激综合征的效应机制

肠易激综合征是功能性胃肠病中最常见的一种,其病理生理机制非常复杂。近年来,肠道菌群在肠易激综合征相关研究中发挥了重要作用,肠道微生态失衡、菌群组成及多样性改变、有益菌减少而有害菌增加导致了疾病发生发展,以肠道菌群为导向的治疗手段也逐渐增多。同时,由于药物干预未能取得满意的疗效,在寻求替代疗法的过程中,针灸因其应用广泛、不良反应少而备受关注。相关研究表明针灸可以通过影响肠道菌群来调节肠道功能,改善肠易激综合征的症状。因此,本研究旨在论述肠道菌群与肠易激综合征的关系,并从调节肠道菌群的角度探讨针灸治疗肠易激综合征的效应机制。

Immune cell signatures and causal association with irritable bowel syndrome:A mendelian randomization study

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.

基于“脑-肠-菌”轴探讨健脾益气自拟方对老年慢传输型便秘的影响

目的基于“脑-肠-菌”轴理论,探究健脾益气自拟方对老年慢传输型便秘的临床疗效及作用机制。方法回顾性选取湖南中医药大学第一附属医院胃肠外科门诊2021年1月至2023年12月的128例气虚型老年慢传输型便秘患者,随机分为空白组(17例)、对照组(48例)和观察组(63例)。空白组仅进行饮食、生活调整;对照组在空白组基础上口服枸橼酸莫沙必利分散片(5 mg/次,3次/d);观察组在空白组基础上予健脾益气自拟方干预,每日1剂,水煎服,分两次服用。3组均干预6周,对比各组血清脑肠肽[血管活性肠肽(vasoactive intestinal peptide,VIP)、血清5-羟色胺(5-hydroxytryptamine,5-HT)、P物质(substance P,SP)]水平、肠道菌群丰度、结肠传输功能、完全自主排便次数(complete spontaneous bowel movements,CSBM)、便秘患者生存质量自评量表(Patient Assessment of Constipation-Quality of Life,PAC-QOL)评分及临床疗效。结果与治疗前比较,治疗后3组乳酸杆菌菌群数量均升高(P<0.05,P<0.01),血清VIP水平及PAC-QOL评分降低(P<0.05,P<0.01)。与空白组比较,对照组和观察组双歧杆菌、类杆菌数量、血清5-HT、血清SP水平均升高(P<0.01),肠杆菌、梭杆菌数量、血清VIP水平、PAC-QOL评分均降低(P<0.05,P<0.01)。与对照组比较,观察组双歧杆菌、乳酸杆菌、类杆菌数量、血清5-HT、血清SP、CSBM水平均升高(P<0.01);肠杆菌、梭杆菌数量、血清VIP水平、PAC-QOL评分均降低(P<0.05,P<0.01),72 h标记物残留粒数减少(P<0.01)。与空白组比较,对照组和观察组总有效率升高(P<0.05,P<0.01);与对照组比较,观察组总有效率升高(P<0.01)。结论健脾益气自拟方可通过调节“脑-肠-菌”轴,有效改善老年气虚慢传输型便秘患者血清脑肠肽水平,促进肠道菌群平衡,增强结肠传输功能,缓解临床症状,具有临床推广价值。