腹泻型肠易激综合征动物模型评价的研究进展

肠易激综合征(irritable bowel syndrome, IBS)是常见的功能性肠病之一,其中腹泻型肠易激综合征(diarrhea-predominant IBS,IBS-D)占比最多,发病机制复杂多样,且缺少临床特效药。动物模型的制备是进一步研究疾病机制、评价临床药效以及药物开发的重要基础,而模型制备和评价标准关乎研究的质量。本文通过查阅国内外文献及结合本课题组的前期建模经验,基于IBS-D目前公认的发病机制出发,从腹泻情况观察,内脏敏感性测定,肠道动力测定等方面系统总结IBS-D动物模型的评价方法,以期为今后研究提供参考。     

肠道菌群与肠易激综合征的研究进展

肠易激综合征(irritable bowel syndrome,IBS)是一种复杂多因素肠道功能性疾病,越来越多的研究显示肠道菌群变化与IBS高度相关,本研究着重IBS肠道菌群改变及其肠道菌群检测方法改进作一综述。     

后生元缓解胃肠道疾病的研究进展及其潜在机制

胃肠道是全身代谢最活跃的器官之一，也是人体内最大的细菌库。人体胃肠道中含有丰富的微生物群，其与宿主健康存在着错综复杂的关系。肠道菌群处于一种动态平衡的状态，当这种平衡被打破时会引起便秘、腹泻、肠易激综合征、炎症性肠病和结直肠癌等胃肠道疾病的发生。近年来，关于后生元的研究越来越多，其对肠道屏障的保护作用与益生菌类似甚至效果更佳。本文重点介绍了当前后生元在动物实验和临床中改善胃肠道疾病的相关研究，探讨了后生元在胃肠道中的作用及其在增强上皮屏障、调节免疫系统、肠道菌群和神经系统4个方面的潜在作用机制。     

肠道稳态与肠易激综合征

肠易激综合征(Irritable bowel syndrome,IBS)是一种常见的功能性胃肠病,其具体发病机制尚不清楚。近年来的研究显示肠道稳态的改变(主要表现为菌群失调)与IBS病理生理机制密切相关。流行病学研究表明IBS的发展往往会破坏肠道正常菌群的稳定状态,IBS患者组和健康对照组之间肠道菌群结构存在明显差异。此外,动物实验和一些临床研究表明IBS肠道菌群组成的变化与胃肠道和脑—肠轴功能异常密切相关,而这些也是IBS患者常表现出的临床症状。本研究综述了微生物群—脑—肠轴相互作用对IBS发生发展的影响,帮助深入对IBS的认识并指导临床。     

腹泻型IBS患者小肠细菌过度生长和抗菌素的影响

目的观察腹泻型肠易激综合征(IBS-D)患者乳果糖氢呼气试验(LHBT)的阳性率、以及短期抗菌素治疗的疗效。方法 89例符合罗马Ⅲ标准的IBS-D患者接受LHBT检测,分析LHBT结果与肠易激综合征(IBS)症状的相关性;16例LHBT阳性IBS-D患者接受"替硝唑或司帕沙星"治疗1周,观察LHBT阴转率及其与症状改善的关系。结果 89例IBS-D患者中,46例(51.7%)LHBT阳性。LHBT阳性组与LHBT阴性组IBS患者在腹痛程度和频率、腹胀程度和频率的差异有统计学意义(P0.05)。16例LHBT阳性的IBS-D患者经1周抗菌素治疗后10例(62.5%)LHBT阴转,IBS症状改善率(Y)与H2呼出量减少率(X)存在正相关关系(回归方程Y=31.3+0.34X,r=0.61,P=0.03)。结论 51.7%IBS-D患者存在小肠细菌过生长(SIBO),SIBO与IBS-D患者的腹痛、腹胀症状有关;短程抗菌素治疗后可以使IBS-D的部分症状获得缓解。     

肠道微生物代谢物在肠易激综合征中的研究进展

肠易激综合征(irritable bowel syndrome, IBS)是常见的胃肠道功能障碍疾病,以腹痛、腹胀、排便习惯改变等为典型临床症状。尽管IBS病因复杂且发病机制并未完全阐明,但越来越多的文献报道其发病与微生物-肠-脑轴调控失常密切相关。本文以肠道微生物衍生的代谢物神经递质、短链脂肪酸和胆汁酸代谢物为切入点,对其在内脏敏感、腹痛、腹泻和精神心理障碍等IBS症状发展中的作用进行系统综述,为以代谢物转化细菌为靶点治疗IBS提供理论支撑。     

Science子刊:肠道细菌或可改变肠道和大脑的功能

正日前,一项刊登在国际杂志Science Translational Medicine上的研究报告中,来自麦克马斯特大学的研究人员通过研究发现,肠道中的细菌或许能够影响肠道易激综合征(irritable bowel syndrome,IBS)患者机体肠道和行为的症状,相关研究或为研究人员开发微生物定向疗法提供了新的思路和见解。肠道易激综合征是一种常见的胃肠道疾病,其会影响机体的大肠组织,而患者也会遭受腹痛以及排便习惯的改变,比如腹泻和便秘等,通常     

肠道菌群失衡诱发肠易激综合征的机制

肠易激综合征(irritable bowel syndrome,IBS)是一种常见的功能性胃肠道疾病,严重地威胁着人类的健康与生存质量。最近的研究发现IBS的发病机制是复杂多样的,尽管其确切的发病原因尚不完全清楚,但有证据显示IBS可能与肠道菌群失衡有关。本文就有关肠道菌群的功能、IBS患者肠道菌群的特点、肠道菌群失衡导致IBS发病的可能机制的研究进展作一综述,旨在为IBS的早期诊断与有效治疗提供有价值的理论依据。     

胃肠道菌群与肿瘤发生的关系

人体的胃肠道菌群构成一个庞大、复杂的微生态系统,并且随着年龄的增长而发生动态变化,成年后菌群的结构达到动态平衡。胃肠道菌群具有参与物质代谢、促进机体免疫系统的发育和抑制病原菌定植等生理作用。菌群失调会导致各种疾病的发生,如肠易激综合征、炎症性肠病、肥胖症、1型糖尿病、肠道恶性肿瘤等。本文就胃肠道菌群与肿瘤发生发展关系的最新研究作一综述,并根据最新提出的Alpha-Bug学说和driver-passenger学说,论述了肠道菌群促进大肠癌发生的机制。为阐明胃肠道肿瘤的发生机制提供新的思路。     

肠易激综合征患者肠道灌洗液菌群特点

目的探讨肠易激综合征(IBS)患者肠道灌洗液菌群特点及其临床意义。方法选择2018年10月至2019年10月我院收治的87例肠易激综合征患者为病例组,选择同期我院健康体检者87例为对照组,比较两组对象肠道灌洗液菌群分布,比较不同类型及不同严重程度肠易激综合征患者肠道灌洗液菌群失调情况。采用Spearman相关分析肠易激综合征患者肠道灌洗液菌群失调与疾病类型、症状严重程度的相关性。结果病例组患者肠道乳杆菌、双歧杆菌、双歧杆菌与肠杆菌数量之比(B/E值)显著低于对照组(t=8.097、8.370、8.255,均P0.001),而肠球菌、肠杆菌数量显著高于对照组(t=11.577、8.424,均P0.001)。不同类型肠易激综合征患者I度、Ⅲ度肠道灌洗液菌群失调比例差异具有统计学意义(t=30.548、19.145,均P0.001),而不同类型肠易激综合征患者Ⅱ度肠道灌洗液菌群失调比例差异无统计学意义(t=2.435,P=0.296)。不同严重程度肠易激综合征患者Ⅰ度、Ⅲ度肠道灌洗液菌群失调比例差异有统计学意义(t=8.460、14.872,均P0.001),而不同严重程度肠易激综合征患者Ⅱ度肠道灌洗液菌群失调比例差异无统计学意义(t=0.923,P=0.631)。肠易激综合征患者肠道灌洗液菌群失调与疾病类型、症状严重程度具有显著相关性(r=0.452、0.586,均P0.001)。结论肠易激综合征患者存在肠道灌洗液菌群失调情况,不同疾病类型及症状严重程度的患者肠道灌洗液菌群失调情况存在明显差异,临床可根据其肠道灌洗液菌群变化情况给予针对性治疗。     

The networks of human gut microbe–metabolite associations are different between health and irritable bowel syndrome

The goal of this study was to determine if fecal metabolite and microbiota profiles can serve as biomarkers of human intestinal diseases, and to uncover possible gut microbe–metabolite associations. We employed proton nuclear magnetic resonance to measure fecal metabolites of healthy children and those diagnosed with diarrhea-predominant irritable bowel syndrome (IBS-D). Metabolite levels were associated with fecal microbial abundances. Using several ordination techniques, healthy and irritable bowel syndrome (IBS) samples could be distinguished based on the metabolite profiles of fecal samples, and such partitioning was congruent with the microbiota-based sample separation. Measurements of individual metabolites indicated that the intestinal environment in IBS-D was characterized by increased proteolysis, incomplete anaerobic fermentation and possible change in methane production. By correlating metabolite levels with abundances of microbial genera, a number of statistically significant metabolite–genus associations were detected in stools of healthy children. No such associations were evident for IBS children. This finding complemented the previously observed reduction in the number of microbe–microbe associations in the distal gut of the same cohort of IBS-D children.     

Lower gastrointestinal disorders in patients with irritable bowel syndrome

Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal system characterized by abdominal pain related to bowel emptying, defecation impairment and abdominal distention. The aim of the study was to objectify lower gastrointestinal system disturbances in IBS patients. Thirty IBS patients and 30 healthy subjects were included in the study. IBS patients were divided into two subgroups: IBS with predominant diarrhea (IBSd) and IBS with predominant constipation (IBSc). All study subjects underwent physical examination (including digitorectal examination), standard laboratory testing and anorectal manometry. Endoscopy was performed only in group of IBS patients. A statistically significant difference was recorded in most manometric parameters between healthy subjects and IBS patients, which was even more pronounced in IBSd patients. Study results showed that the intestinal motility disorder underlying IBS could be objectified by use of anorectal manometry.     

Endocannabinoid and Cannabinoid-Like Fatty Acid Amide Levels Correlate with Pain-Related Symptoms in Patients with IBS-D and IBS-C: A Pilot Study

Aims

Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder, associated with alterations of bowel function, abdominal pain and other symptoms related to the GI tract. Recently the endogenous cannabinoid system (ECS) was shown to be involved in the physiological and pathophysiological control of the GI function. The aim of this pilot study was to investigate whether IBS defining symptoms correlate with changes in endocannabinoids or cannabinoid like fatty acid levels in IBS patients.

Methods

AEA, 2-AG, OEA and PEA plasma levels were determined in diarrhoea-predominant (IBS-D) and constipation-predominant (IBS-C) patients and were compared to healthy subjects, following the establishment of correlations between biolipid contents and disease symptoms. FAAH mRNA levels were evaluated in colonic biopsies from IBS-D and IBS-C patients and matched controls.

Results

Patients with IBS-D had higher levels of 2AG and lower levels of OEA and PEA. In contrast, patients with IBS-C had higher levels of OEA. Multivariate analysis found that lower PEA levels are associated with cramping abdominal pain. FAAH mRNA levels were lower in patients with IBS-C.

Conclusion

IBS subtypes and their symptoms show distinct alterations of endocannabinoid and endocannabinoid-like fatty acid levels. These changes may partially result from reduced FAAH expression. The here reported changes support the notion that the ECS is involved in the pathophysiology of IBS and the development of IBS symptoms.     

肠黏膜屏障与肠道菌群的相互关系

摘要：人类肠道中微生物群与肠道环境相互作用以维持机体健康。肠黏膜屏障主要由黏液层、肠道菌群、肠道免疫系统和肠上皮细胞本身的完整性等构成。肠道作为直接与大量菌群接触的器官,其屏障功能在肠道健康中的作用尤为显著。肠道菌群与肠道屏障相互作用,保持肠道菌群与肠道屏障相对稳定,肠道菌群参与肠道免疫反应的建立,共同建立机体天然防御系统,在保持肠道免疫的动态平衡中具有重要作用。当两者之间的平衡被打破时,可诱发功能性胃肠病（如肠易激综合征）及免疫相关性疾病（如炎症性肠病）。本文主要阐述肠黏膜屏障与肠道菌群之间的相互关系以及与肠道屏障功能障碍相关的肠道疾病。     

疏肝健脾针法对肝郁脾虚证腹泻型肠易激综合征患者肠道菌群和血清5-HT、NPY、CGRP的影响

目的:观察疏肝健脾针法治疗肝郁脾虚证腹泻型肠易激综合征(IBS-D)的临床疗效及对肠道菌群和血清5-羟色胺(5-HT)、降钙素基因相关肽(CGRP)、神经肽Y(NPY)的影响。方法:96例肝郁脾虚证IBS-D患者均来自天津市人民医院2018年5月~2021年2月期间收治的门诊或住院患者。根据双色球法将患者分为对照组和研究组,各为48例,对照组接受西医治疗,研究组在对照组基础上结合疏肝健脾针法治疗,对比两组疗效、中医证候积分、肠道菌群和血清5-HT、NPY、CGRP水平变化。结果:研究组的临床总有效率明显高于对照组(P<0.05)。疗程结束后,研究组大便稀溏、少腹胀痛、食后腹胀、食欲减退、精神疲乏、口苦口黏、四肢无力、烦躁易急、畏寒怕冷症状积分均低于对照组(P<0.05)。疗程结束后,研究组血清5-HT、NPY、CGRP水平均低于对照组(P<0.05)。疗程结束后,研究组双歧杆菌、双歧杆菌/大肠杆菌比值、乳酸杆菌数量均高于对照组,而大肠杆菌数量低于对照组(P<0.05)。结论:疏肝健脾针法治疗肝郁脾虚证IBS-D患者,可有效促进症状改善,调节肠道菌群,降低血清5-HT、NPY、CGRP水平,临床疗效显著。     

Intestinal microbiota in healthy adults: temporal analysis reveals individual and common core and relation to intestinal symptoms

Background

While our knowledge of the intestinal microbiota during disease is accumulating, basic information of the microbiota in healthy subjects is still scarce. The aim of this study was to characterize the intestinal microbiota of healthy adults and specifically address its temporal stability, core microbiota and relation with intestinal symptoms. We carried out a longitudinal study by following a set of 15 healthy Finnish subjects for seven weeks and regularly assessed their intestinal bacteria and archaea with the Human Intestinal Tract (HIT)Chip, a phylogenetic microarray, in conjunction with qPCR analyses. The health perception and occurrence of intestinal symptoms was recorded by questionnaire at each sampling point.

Principal Findings

A high overall temporal stability of the microbiota was observed. Five subjects showed transient microbiota destabilization, which correlated not only with the intake of antibiotics but also with overseas travelling and temporary illness, expanding the hitherto known factors affecting the intestinal microbiota. We identified significant correlations between the microbiota and common intestinal symptoms, including abdominal pain and bloating. The most striking finding was the inverse correlation between Bifidobacteria and abdominal pain: subjects who experienced pain had over five-fold less Bifidobacteria compared to those without pain. Finally, a novel computational approach was used to define the common core microbiota, highlighting the role of the analysis depth in finding the phylogenetic core and estimating its size. The in-depth analysis suggested that we share a substantial number of our intestinal phylotypes but as they represent highly variable proportions of the total community, many of them often remain undetected.

Conclusions/Significance

A global and high-resolution microbiota analysis was carried out to determine the temporal stability, the associations with intestinal symptoms, and the individual and common core microbiota in healthy adults. The findings provide new approaches to define intestinal health and to further characterize the microbial communities inhabiting the human gut.