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.     

Gut dysbiosis and irritable bowel syndrome: The potential role of probiotics

Objective

To discuss the role of gut dysbiosis in the development of irritable bowel syndrome (IBS) and the impact of probiotics as a potential therapeutic measure.

Impact of psychological stress on irritable bowel syndrome

Psychological stress is an important factor for the development of irritable bowel syndrome (IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brain. In the present review we discuss the potential role of psychological stress in the pathogenesis of IBS and provide comprehensive approaches in clinical treatment. Evidence from clinical and experimental studies showed that psychological stresses have marked impact on intestinal sensitivity, motility, secretion and permeability, and the underlying mechanism has a close correlation with mucosal immune activation, alterations in central nervous system, peripheral neurons and gastrointestinal microbiota. Stress-induced alterations in neuro-endocrine-immune pathways acts on the gut-brain axis and microbiota-gut-brain axis, and cause symptom flare-ups or exaggeration in IBS. IBS is a stress-sensitive disorder, therefore, the treatment of IBS should focus on managing stress and stress-induced responses. Now, non-pharmacological approaches and pharmacological strategies that target on stress-related alterations, such as antidepressants, antipsychotics, miscellaneous agents, 5-HT synthesis inhibitors, selective 5-HT reuptake inhibitors, and specific 5-HT receptor antagonists or agonists have shown a critical role in IBS management. A integrative approach for IBS management is a necessary.     

肠易激综合征患者脑部痛觉功能区域的变化

目的应用血氧水平依赖性功能性磁共振(BOLD fMRI)技术研究肠易激综合征(irritablebowelsyndrome ,IBS)患者颅内痛觉功能区的变化及临床意义并比较与正常人的差异。方法2 0 0 2年1月～2 0 0 4年2月期间,参照罗马II诊断标准纳入67例肠易激综合征患者和10例正常志愿者,其中腹泻型肠易激综合征44例,男19例,女2 5例。年龄3 4～73岁,平均年龄5 3 0 7±8 44岁。便秘型肠易激综合征2 3例,其中男12例,女11例,年龄2 1～74岁,平均年龄46 2 2±14 64岁。直肠注气试验记录感觉阈值和感觉评分;功能性磁共振(fMRI)分析直肠扩张3 0ml、60ml、90ml和12 0ml时颅内痛觉功能区扣带前皮质(ACC)、脑岛皮质(IC)、额前皮质(PFC)及丘脑(THAL)的激活面积和强度。结果腹泻型IBS患者排便急迫和疼痛阈值显著低于便秘型患者和正常志愿者(P <0 0 5 ) ;腹泻型IBS患者在直肠注气90ml和12 0ml时视觉模拟评分(VAS)显著高于正常志愿者(P <0 0 5 ) ;便秘型IBS患者直肠扩张12 0ml时额前皮质、右侧丘脑兴奋面积较正常对照组显著增高(P <0 0 5 ) ,腹泻型IBS患者直肠扩张12 0ml时右侧脑岛皮质、额前皮质和右侧丘脑的兴奋面积较正常对照组显著增高(P <0 0 5 ) ;所有IBS患者直肠扩张90ml时脑岛皮质、直肠扩张12 0ml时脑岛皮质、额前皮质和丘脑     

Sex hormones in the modulation of irritable bowel syndrome

Compelling evidence indicates sex and gender differences in epidemiology,symptomatology,pathophysiology,and treatment outcome in irritable bowel syndrome(IBS).Based on the female predominance as well as the correlation between IBS symptoms and hormonal status,several models have been proposed to examine the role of sex hormones in gastrointestinal(GI)function including differences in GI symptoms expression in distinct phases of the menstrual cycle,in pre-and post-menopausal women,during pregnancy,hormonal treatment or after oophorectomy.Sex hormones may influence peripheral and central regulatory mechanisms of the brain-gut axis involved in the pathophysiology of IBS contributing to the alterations in visceral sensitivity,motility,intestinal barrier function,and immune activation of intestinal mucosa.Sex differences in stress response of the hypothalamic-pituitary-adrenal axis and autonomic nervous system,neuroimmune interac-tions triggered by stress,as well as estrogen interactions with serotonin and corticotropin-releasing factor signaling systems are being increasingly recognized.A concept ofmicrogenderomerelated to the potential role of sex hormone modulation of the gut microbiota is also emerging.Significant differences between IBS female and male patients regarding symptomatology and comorbidity with other chronic pain syndromes and psychiatric disorders,together with differences in efficacy of serotonergic medications in IBS patients confirm the necessity for more sex-tailored therapeutic approach in this disorder.     

磁共振成像技术在分析肠易激综合征患者脑功能中的应用

目的应用脑部功能性磁共振成像(fMRI)技术探究肠易激综合征(IBS)的病理生理机制中大脑功能区变化,并评价精神心理因素在其发病中的意义。方法收集31例IBS患者和20位正常对照者在不同容量直肠气囊刺激下获得的fMRI图像,并应用医院焦虑抑郁量表(HADS)进行精神心理因素评分,对结果进行统计学分析。结果 IBS患者的fMRI图像在不同容量地刺激下存在差异,并且脑部激活区域随着直肠气囊扩张容量的增加而不断扩大,激活区域的显示也越来越明显;而在正常对照者中的差异无统计学意义。结论 IBS患者的内脏敏感性与大脑皮质的活动性相关,但需要更大的样本量验证。而IBS患者内脏敏感性的程度是否与精神心理因素有必然的联系,还有待进一步的研究及验证。     

Global research trends in the microbiome related to irritable bowel syndrome: A bibliometric and visualized study

BACKGROUNDIrritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Dysregulation of the gut–brain axis plays a central role in the pathophysiology of IBS. It is increasingly clear that the microbiome plays a key role in the development and normal functioning of the gut–brain axis.AIMTo facilitate the identification of specific areas of focus that may be of relevance to future research. This study represents a bibliometric analysis of the literature pertaining to the microbiome in IBS to understand the development of this field. METHODSThe data used in our bibliometric analysis were retrieved from the Scopus database. The terms related to IBS and microbiome were searched in titles or abstracts within the period of 2000–2019. VOSviewer software was used for data visualization. RESULTSA total of 13055 documents related to IBS were retrieved at the global level. There were 1872 scientific publications focused on the microbiome in IBS. There was a strong positive correlation between publication productivity related to IBS in all fields and productivity related to the microbiome in IBS (r = 0.951, P < 0.001). The United States was the most prolific country with 449 (24%) publications, followed by the United Kingdom (n = 176, 9.4%), China (n = 154, 8.2%), and Italy (n = 151, 8.1%). The h-index for all retrieved publications related to the microbiome in IBS was 138. The hot topics were stratified into four clusters: (1) The gut–brain axis related to IBS; (2) Clinical trials related to IBS and the microbiome; (3) Drug-mediated manipulation of the gut microbiome; and (4) The role of the altered composition of intestinal microbiota in IBS prevention. CONCLUSIONThis is the first study to evaluate and quantify global research productivity pertaining to the microbiome in IBS. The number of publications regarding the gut microbiota in IBS has continuously grown since 2013. This finding suggests that the future outlook for interventions targeting the gut microbiota in IBS remains promising.     

Intestinal microbiota in pathophysiology and management of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 10¹⁴ cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS.     

COVID-19 as a trigger of irritable bowel syndrome: A review of potential mechanisms

In December 2019 a novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started spreading from Wuhan city of Chinese Hubei province and rapidly became a global pandemic. Clinical symptoms of the disease range from paucisymptomatic disease to a much more severe disease. Typical symptoms of the initial phase include fever and cough, with possible progression to acute respiratory distress syndrome. Gastrointestinal manifestations such as diarrhoea, vomiting and abdominal pain are reported in a considerable number of affected individuals and may be due to the SARS-CoV-2 tropism for the peptidase angiotensin receptor 2. The intestinal homeostasis and microenvironment appear to play a major role in the pathogenesis of COVID-19 and in the enhancement of the systemic inflammatory responses. Long-term consequences of COVID-19 include respiratory disturbances and other disabling manifestations, such as fatigue and psychological impairment. To date, there is a paucity of data on the gastrointestinal sequelae of SARS-CoV-2 infection. Since COVID-19 can directly or indirectly affect the gut physiology in different ways, it is plausible that functional bowel diseases may occur after the recovery because of potential pathophysiological alterations (dysbiosis, disruption of the intestinal barrier, mucosal microinflammation, post-infectious states, immune dysregulation and psychological stress). In this review we speculate that COVID-19 can trigger irritable bowel syndrome and we discuss the potential mechanisms.     

Immunomodulation of enteric neural function in irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder which is characterised by symptoms such as bloating, altered bowel habit and visceral pain. It’s generally accepted that miscommunication between the brain and gut underlies the changes in motility, absorpto-secretory function and pain sensitivity associated with IBS. However, partly due to the lack of disease-defining biomarkers, understanding the aetiology of this complex and multifactorial disease remains elusive. Anecdotally, IBS patients have noted that periods of stress can result in symptom flares and many patients exhibit co-morbid stress-related mood disorders such as anxiety and depression. However, in addition to psychosocial stressors, infection-related stress has also been linked with the initiation, persistence and severity of symptom flares. Indeed, prior gastrointestinal infection is one of the strongest predictors of developing IBS. Despite a lack of overt morphological inflammation, the importance of immune factors in the pathophysiology of IBS is gaining acceptance. Subtle changes in the numbers of mucosal immune cell infiltrates and elevated levels of circulating pro-inflammatory cytokines have been reproducibly demonstrated in IBS populations. Moreover, these immune mediators directly affect neural signalling. An exciting new area of research is the role of luminal microbiota in the modulation of neuro-immune signalling, resulting in local changes in gastrointestinal function and alterations in central neural functioning. Progress in this area has begun to unravel some of the complexities of neuroimmune and neuroendocrine interactions and how these molecular exchanges contribute to GI dysfunction     

Novel evidence for hypersensitivity of visceral sensory neural circuitry in irritable bowel syndrome patients

BACKGROUND & AIMS: Visceral hypersensitivity in irritable bowel syndrome (IBS) patients has been documented by evaluation of perceived stimulations that can reflect abnormalities of both sensory neurocircuitry and cognitive processes. The presence of actual neurohypersensitivity in human beings has not been documented separately. Because subliminal stimulations are free from the influence of stimulus-related cognitive processes, functional magnetic resonance imaging (fMRI) cortical response to these stimuli can be considered a measure of activity of the neural circuitry alone. The aim of this study was to compare quantitatively the cerebral cortical fMRI activity response to equal subliminal stimulations between IBS patients and age-matched controls. METHODS: We studied 10 IBS patients and 10 healthy controls using a computerized barostat-controlled rectal distention device. fMRI activity volume and percent maximum signal intensity change for equal subliminal distention pressures were compared between controls and patients. RESULTS: Three levels of subliminal distention pressures (eg, 10, 15, and 20 mm Hg), were represented in both controls and patients and were analyzed for fMRI response. In all 3 distention levels the fMRI activity volume in IBS patients was significantly larger than age- and sex-matched controls (P < .05). The percent maximum signal intensity change was similar between IBS patients and controls. CONCLUSIONS: The volume of cerebral cortical activity response to equal subliminal distention pressures in IBS patients is significantly larger than in controls, documenting the existence of hypersensitivity of the neural circuitry in this patient group irrespective of stimulus-related cognitive processes.     

Role of negative affects in pathophysiology and clinical expression of irritable bowel syndrome

Irritable bowel syndrome(IBS)is regarded as a multifactorial disease in which alterations in the brain-gut axis signaling play a major role.The biopsychosocial model applied to the understanding of IBS pathophysiology assumes that psychosocial factors,interacting with peripheral/central neuroendocrine and immune changes,may induce symptoms of IBS,modulate symptom severity,influence illness experience and quality of life,and affect outcome.The present review focuses on the role of negative affects,including depression,anxiety,and anger,on pathogenesis and clinical expression of IBS.The potential role of the autonomic nervous system,stress-hormone system,and immune system in the pathophysiology of both negative affects and IBS are taken into account.Psychiatric comorbidity and subclinical variations in levels of depression,anxiety,and anger are further discussed in relation to the main pathophysiological and symptomatic correlates of IBS,such as sensorimotor functions,gut microbiota,inflammation/immunity,and symptom reporting.     

Gut microbiota role in irritable bowel syndrome: New therapeutic strategies

In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome(IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial(Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful(Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.     

Economic burden of irritable bowel syndrome in China

AIM To estimate annual direct and indirect costs for patients diagnosed with irritable bowel syndrome(IBS) and subtypes.METHODS Patients completed a standardized questionnaire concerning usage of healthcare resources, travel costs, meals, and productivity loss of patients when seeking treatment for IBS. Total annual costs per patient were calculated as the sum of direct(including medical and nonmedical) and indirect costs. Total annual costs per patient among various IBS subtypes were compared. Analysis of variance and bootstrapped independent sample t-tests were performed to determine differences between groups after controlling for IBS subtypes.RESULTS A total of 105 IBS patients(64.80% female), mean age of 57.12 years ± 10.31 years), mean disease duration of 4.31 years ± 5.40 years, were included. Total annual costs per patient were estimated as CNy18262.84(USD2933.08). Inpatient and outpatient healthcare use were major cost drivers, accounting for 46.41%and 23.36% of total annual costs, respectively. Productivity loss accounted for 25.32% of total annual costs. The proportions of direct and indirect costs were similarto published studies in other countries. Nationally, the total costs of managing IBS would amount to CNy123.83 billion(USD1.99 billion). Among the IBS subtypes, total annual costs per patient of IBS-M was highest at CNy18891.18(USD3034). Furthermore, there was significant difference in productivity loss among IBS subtypes(P = 0.031).CONCLUSION IBS imposes a huge economic burden on patients and healthcare systems, which could account for 3.3% of the total healthcare budget for the entire Chinese nation. More than two-thirds of total annual costs of IBS consist of inpatient and outpatient healthcare use. Among the subtypes, IBS-M patients appear to have the greatest economic burden but require further confirmation.     

Bran and irritable bowel syndrome: The primary-care perspective

BACKGROUND: We have shown that bran exacerbates irritable bowel syndrome symptoms in a large proportion of secondary-care patients. However, it is unknown if this also happens in primary-care or whether a better response to bran occurs, leading to bran failures being selected for referral to the specialist. AIMS: To assess the response to bran in primary-care irritable bowel syndrome comparing it to that obtained in secondary-care. PATIENTS AND METHODS: One hundred consecutive primary-care irritable bowel syndrome patients were asked how bran or soluble fibre products affected their symptoms. RESULTS: Bran improved symptoms in 27% of primary-care and 10% of secondary-care patients (p<0.01) and exacerbated symptoms in 22% of primary-care and 55% of secondary-care patients (p<0.001). Fifty-one percent of primary-care and 33% of secondary-care patients reported no change with bran. In primary-care, proprietary fibre led to improvement in 25%, deterioration in 19% and no change in 56% which was not significantly different to secondary-care. CONCLUSION: Although not especially effective in primary-care irritable bowel syndrome patients, bran does not cause so many problems and is more helpful than in secondary-care. The effects of soluble fibre are similar in both primary-care and secondary-care. This study highlights the problem of extrapolating the response to treatment in irritable bowel syndrome from different care settings.     

粪菌移植对肠易激综合征临床疗效和肠道菌群影响的非对照初步研究

目的:探讨粪菌移植治疗IBS的有效性、安全性及其对IBS患者肠道菌群的影响。方法:选择2016年9月至2017年8月在广州市第一人民医院行粪菌移植的IBS住院患者28例。所有IBS患者于粪菌移植前、粪菌移植后4和12周完成肠易激综合征生活质量量表(IBS-QOL)、肠易激综合征严重程度系统评分(IBS-SSS)和胃肠道...     

青岛地区感染后肠易激综合征的临床特点

目的 调查分析青岛地区感染后肠易激综合征(PI-IBS)患者的临床特点.方法 收集门诊1BS患者,采用问卷调查方式,内容包括一般资料、症状和微生态制剂治疗前后的生活质量表.结果 (1)PI-IBS患者中女性患病率是男性的2.2倍,与非感染后肠易激综合征(non-PI-IBS)相近;(2)PI-IBS与non-PI-IBS患者都以脑力劳动者居多;(3)PI-IBS与non-PI-IBS患者的消化系统以外的伴随症状中,以躯体性不适为主的表现(疲劳、头痛、头晕、背痛等)的差异无统计学意义(X<'2>=10.5,P>0.05),而以精神性不适为主的表现(紧张、多疑、抑郁、焦虑等)PI-IBS要明显多于non-PI-IBS,差异有统计学意义(X<'2>=28.7,P<0.05);(4)PI-IBS的肠道菌群失调率明显高于non-PI-IBS患者;(5)PI-IBS患者在双歧三联活菌治疗1个月后,生活质最评分的差异有统计学意义(t=3.8,P<0.01),而non-PI-IBS患者治疗前后的差异无统计学意义(t=1.5,P>0.05).结论 青岛地区PI-IBS与non-PI-IBS的某些临床特点存在差异.     

中国肠易激综合征流行病学调查现状分析

目的为了全面了解国内肠易激综合征(IBS)流行病学调查现状,特别是研究中的不足,以更好地指导今后流行病学研究,我们对国内IBS流行病学调查文献进行了分析。方法对2000年1月-2012年6月在国内期刊发表的有关IBS流行病学调查文献,以"肠易激综合征"和"流行病学"为关键词进行检索,并进行综合分析。结果 43篇有关IBS流行病学调查的文章发表在32种期刊杂志,调查范围涉及全国26个省市自治区,单个调查的样本量58～16727例,研究人群包括普通人群、特殊人群和IBS患者。72.1%研究采用了整群分层随机抽样的方法。有24项研究应用罗马Ⅱ标准,5项研究联合应用罗马Ⅱ和Manning标准,12项研究应用罗马Ⅲ标准。我国IBS患病率存在较大差异,流行病学研究诸多环节可能对调查结果产生影响。影响IBS发病和患病率的因素包括:心理、饮食、年龄、性别、胃肠道感染史、情绪压力、职业、服药史等。结论在我国,IBS的流行病学调查研究水平有待进一步提高。     

肠易激综合征患者的述情障碍及人格特征调查

目的调查肠易激综合征(IBS)患者述情障碍及人格特征对发病的影响。方法 2010年至2011年对云南省第二人民医院消化科门诊的126例IBS患者进行多伦多述情障碍及艾森克人格问卷调查。结果 IBS患者存在一定的述情障碍,且男性的述情障碍[在因子Ⅱ(缺乏认识和区别情感及躯体感受的能力)和因子Ⅲ(少幻想)方面]比女性患者更明显。IBS患者存在一定的性格特质,女性患者在神经质方面比男性患者明显。同时,其述情障碍与性格特质有关。结论 IBS患者在述情障碍及个性方面存在一定的差异,社会心理因素对发病有一定的影响。