Emerging role of the gut microbiome in post-infectious irritable bowel syndrome:A literature review

Post-infectious irritable bowel syndrome(PI-IBS)is a particular type of IBS,with symptom onset after an acute episode of infectious gastroenteritis.Despite infectious disease resolution and clearance of the inciting pathogen agent,10%of patients will develop PI-IBS.In susceptible individuals,the exposure to pathogenic organisms leads to a marked shift in the gut microbiota with prolonged changes in host-microbiota interactions.These changes can affect the gut-brain axis and the visceral sensitivity,disrupting the intestinal barrier,altering neuromuscular function,triggering persistent low inflammation,and sustaining the onset of IBS symptoms.There is no specific treatment strategy for PI-IBS.Different drug classes can be used to treat PI-IBS similar to patients with IBS in general,guided by their clinical symptoms.This review summarizes the current evidence for microbial dysbiosis in PI-IBS and analyzes the available data regarding the role of the microbiome in mediating the central and peripheral dysfunctions that lead to IBS symptoms.It also discusses the current state of evidence on therapies targeting the microbiome in the management of PI-IBS.The results of microbial modulation strategies used in relieving IBS symptomatology are encouraging.Several studies on PI-IBS animal models reported promising results.However,published data that describe the efficacy and safety of microbial targeted therapy in PI-IBS patients are scarce.Future research is required.

Post-infectious irritable bowel syndrome:Mechanistic insights into chronic disturbances following enteric infection

Irritable bowel syndrome(IBS)is a commonly encountered chronic functional gastrointestinal(GI)disorder.Approximately 10%of IBS patients can trace the onset of their symptoms to a previous a bout of infectious dysentery.The appearance of new IBS symptoms following an infectious event is defined as post-infectiousIBS.Indeed,with the World Health Organization estimating between 2 and 4 billion cases annually,infectious diarrheal disease represents an incredible international healthcare burden.Additionally,compounding evidence suggests many commonly encountered enteropathogens as unique triggers behind IBS symptom generation and underlying pathophysiological features.A growing body of work provides evidence supporting a role for pathogen-mediated modifications in the resident intestinal microbiota,epithelial barrier integrity,effector cell functions,and innate and adaptive immune features,all proposed physiological manifestations that can underlie GI abnormalities in IBS.Enteric pathogens must employ a vast array of machinery to evade host protective immune mechanisms,and illicit successful infections.Consequently,the impact of infectious events on host physiology can be multidimensional in terms of anatomical location,functional scope,and duration.This review offers a unique discussion of the mechanisms employed by many commonly encountered enteric pathogens that cause acute disease,but may also lead to the establishment of chronic GI dysfunction compatible with IBS.

Montezuma's revenge-the sequel: The one-hundred year anniversary of the first description of “post-infectious” irritable bowel syndrome

One-hundred years have passed since the original description of the commonly described phenomenon of persistent abdominal symptoms being triggered by an acute enteric infection. This first account was generated out of astute observations by Sir Arthur Hurst in World War I. Additional descriptions followed from military and non-military practitioners adding the evidence which has transitioned this recognized condition from association to causation. While mechanistic understanding is an area of active pursuit, this historical accounting of a centuries progress highlights important advances and contributions of military medicine and scientists to advances benefiting global populations.

Is irritable bowel syndrome an infectious disease?

Irritable bowel syndrome(IBS) is the most common of all gastroenterological diseases. While many mechanisms have been postulated to explain its etiology, no single mechanism entirely explains the heterogeneity of symptoms seen with the various phenotypes of the disease. Recent data from both basic and clinical sciences suggest that underlying infectious disease may provide a unifying hypothesis that better explains the overall symptomatology. The presence of small intestinal bowel overgrowth(SIBO) has been documented in patients with IBS and reductions in SIBO as determined by breath testing correlate with IBS symptom improvement in clinical trials. The incidence of new onset IBS symptoms following acute infectious gastroenteritis also suggests an infectious cause. Alterations in microbiota-host interactions may compromise epithelial barrier integrity, immune function, and the development and function of both central and enteric nervous systems explaining alterations in the brain-gut axis. Clinical evidence from treatment trials with both probiotics and antibiotics also support this etiology. Probiotics appear to restore the imbalance in the microflora and improve IBS-specific quality of life. Antibiotic trials with both neomycin and rifaximin show improvement in global IBS symptoms that correlates with breath test normalization in diarrhea-predominant patients. The treatment response to two weeks of rifaximin is sustained for up to ten weeks and comparable results are seen in symptom reduction with retreatment in patients who develop recurrent symptoms.

Effect of mild moxibustion on intestinal microbiota and NLRP6 inflammasome signaling in rats with post-inflammatory irritable bowel syndrome

BACKGROUND About one-third of refractory irritable bowel syndrome(IBS)cases are caused by gastrointestinal(GI)infection/inflammation,known as post-infectious/postinflammatory IBS(PI-IBS).Although it is known that intestinal microbiota and host NOD-like receptor family pyrin domain containing 6(NLRP6)inflammsome signaling are closely related to PI-IBS and moxibustion has a therapeutic effect on PI-IBS,whether moxibustion regulates the intestinal flora and host NLRP6 events in PI-IBS remains unclear.AIM To examine the regulatory effect of moxibustion on intestinal microbiota and host NLRP6 inflammatory signaling in PI-IBS.METHODS Sprague-Dawley rats were divided into a normal control group,a model control group,a mild moxibustion group,and a sham mild moxibustion group.PI-IBS rats in the mild moxibustion group were treated with moxibusiton at bilateral Tianshu(ST 25)and Zusanli(ST36)for 7 consecutive days for 10 min each time.The sham group rats were given the same treatment as the mild moxibustion group except the moxa stick was not ignited.Abdominal withdrawal reflex(AWR)score was measured to assess the visceral sensitivity,and colon histopathology and ultrastructure,colonic myeloperoxidase(MPO)activity,and serum C-reactive protein(CRP)level were measured to evaluate low-grade colonic inflammation in rats.The relative abundance of selected intestinal bacteria in rat feces was detected by 16S rDNA PCR and the NLRP6 inflammsome signaling in the colon was detected by immunofluorescence,qRTPCR,and Western blot.RESULTS The AWR score was significantly decreased and the low-grade intestinal inflammation reflected by serum CRP and colonic MPO levels was inhibited in the mild moxibustion group compared with the sham group.Mild moxibustion remarkably increased the relative DNA abundances of Lactobacillus,Bifidobacterium,and Faecalibacterium prausnitzii but decreased that of Escherichia coli in the gut of PI-IBS rats.Additionally,mild moxibustion induced mRNA and protein expression of intestine lectin 1 but inhibited the expression of IL-1β,IL-18,and resistance-like moleculeβby promoting the NLRP6 and reducing the mRNA and protein expression of apoptosis-associated speck-like protein containing CARD(ASC)and cysteinyl-aspartate-specific proteinase 1(Caspase-1).The relative DNA abundances of Lactobacillus,Bifidobacteria,Faecalibacterium prausnitzii,and Escherichia coli in each group were correlated with the mRNA and protein expression of NLRP6,ASC,and Caspase-1 in the colon.CONCLUSION These findings indicated that mild moxibustion can relieve low-grade GI inflammation and alleviate visceral hypersensitivity in PI-IBS by regulating intestinal microbes and controlling NLRP6 inflammasome signaling.

Irritable bowel syndrome in children:Current knowledge, challenges and opportunities

Irritable bowel syndrome(IBS) is a common and troublesome disorder in children with an increasing prevalence noted during the past two decades. It has a significant effect on the lives of affected children and their families and poses a significant burden on healthcare systems. Standard symptom-based criteria for diagnosis of pediatric IBS have changed several times during the past two decades and there are some differences in interpreting symptoms between different cultures. This has posed a problem when using them to diagnose IBS in clinical practice. A number of potential patho-physiological mechanisms have been described, but so far the exact underlying etiology of IBS is unclear. A few potential therapeutic modalities have been tested in children and only a small number of them have shown some benefit. In addition, most of the described patho-physiological mechanisms and treatment options are based on adult studies. These have surfaced as challenges when dealing with pediatric IBS and they need to be overcome for effective management of children with IBS. Recently suggested top-down and bottom-up models help integrating reported patho-physiological mechanisms and will provide an opportunity for better understanding of the diseases process. Treatment trials targeting single treatment modalities are unlikely to have clinically meaningful therapeutic effects on IBS with multiple integrating patho-physiologies. Trials focusing on multiple combined pharmacological and non-pharmacological therapies are likely to yield more benefit. In addition to treatment, in the future, attention should be paid for possible prevention strategies for IBS.

ICC density predicts bacterial overgrowth in a rat model of post-infectious IBS

AIM:To investigate the interstitial cells of Cajal(ICC) number using a new rat model.METHODS:Sprague-Dawley rats were assigned to two groups.The first group received gavage with Campylobacter jejuni(C.jejuni) 81-176.The second group was gavaged with placebo.Three months after clearance of Campylobacter from the stool,precise segments of duodenum,jejunum,and ileum were ligated in self-contained loops of bowel that were preserved in anaerobic bags.Deep muscular plexus ICC(DMP-ICC) were quantified by two blinded readers assessing the tissue in a random,coded order.The number of ICC per villus was compared among controls,Campylobacter recovered rats without small intestinal bacterial overgrowth(SIBO),and Campylobacter recovered rats with SIBO.RESULTS:Three months after recovery,27% of rats gavaged with C.jejuni had SIBO.The rats with SIBO had a lower number of DMP-ICC than controls in the jejunum and ileum.Additionally there appeared to be a density threshold of 0.12 DMP-ICC/villus that was associated with SIBO.If ileal density of DMP-ICC was < 0.12 ICC/villus,54% of rats had SIBO compared to 9% among ileal sections with > 0.12(P<0.05).If the density of ICC was < 0.12 DMP-ICC/villus in more than one location of the bowel,88% of these had SIBO compared to 6% in those who did not(P<0.001).CONCLUSION:In this post-infectious rat model,the development of SIBO appears to be associated with a reduction in DMP-ICC.Further study of this rat model might help understand the pathophysiology of postinfectious irritable bowel syndrome.

PI-IBS小鼠肠黏膜γδT细胞表型和功能变化的实验研究

目的:探讨PI-IBS小鼠γδT细胞的表型和功能及其在PI-IBS发病中的作用。方法:旋毛虫感染小鼠,观察肠道炎症、腹壁撤退反射(内脏高敏感性)和结肠传输时间(肠道动力)。分别在感染后第2周和第8周处死动物,取末端回肠和近端结肠组织,免疫荧光组化,激光扫描共聚焦显微镜观察肠黏膜γδT细胞的分布和数量变化。收集PI-IBS小鼠肠道淋巴结和脾脏的淋巴细胞,单克隆抗体免疫磁珠分选法分离和纯化γδT细胞,3HTdR法检测其增殖情况,FACS检测其表面分子CD69、CD62L,ELISA检测细胞培养上清液中IFN-γ及IL-17的表达。结果:感染后第2周,PI-IBS小鼠肠道炎症明显,肠黏膜γδT细胞数量明显增加,明显增殖和活化,产生IL-17明显增加(P<0.01)。感染后第8周,PI-IBS小鼠肠道炎症基本消退,动物的腹壁撤退反射和结肠传输试验明显异常。肠黏膜γδT细胞数量仍然明显高于对照组小鼠,仍然有明显增殖、活化和产生IL-17(P<0.01)。结论:肠道γδT细胞增殖、活化及分泌IL-17可能参与PI-IBS的发病。

Preinduced intestinal HSP70 improves visceral hypersensitivity and abnormal intestinal motility in PI-IBS mouse model

Objective:To investigate the impact of the preinduced intestinal heat shock protein 70(HSP70)on the visceral hypersensitivity and abnormal intestinal motility in a post-infectious irritable bowel syndrome(PI-IBS) mouse model.Methods:Eighty-four female C57BL/6 mice were randomly assigned to four groups:control group(n=21) and induction+PI-IBS group(n=21),PI-IBS group(n=21) and induction group(n=21).The mice in PI-IBS group were infected in vivo with trichinella spiralis by oral administration.The visceral hypersensitivity and intestinal motility were evaluated respectively with abdominal withdrawal reflex and colon transportation test.The intestinal HSP70 protein and mRNA level was measured by Western blot and realtime PCR.Meanwhile,the intestinal proinflammatory cytokines IL-10 and TNF-α level was detected by ELISA.Results:Compared with their counterparts in PI-IBS group,the animals in the Induction+PI-IBS group show significantly increased intestinal level of HSP70 and obviously ameliorative clinical tigurcs.including abdominal withdrawal reflex score,intestine transportation time and Bristol scores(P<0.05).Meanwhile,the intestinal post-inflammatory cytokines remarkably changed,including increased IL-10 level and decreased TNF-αlevel(P<0.05).Conclusions:Intestinal IISP70 may play a potential protective role through improving the imbalance between the intestinal post-inflammatory and anti-inflammatory cytokines in PI-IBS.

Post-marketing Re-evaluation of Tongxiening Granules (痛泻宁颗粒) in Treatment of Diarrhea-Predominant Irritable Bowel Syndrome:A Multi-center,Randomized,Double-Blind,Double-Dummy and Positive Control Trial

Objective: To evaluate the efficacy and safety of Tongxiening Granules(痛泻宁颗粒, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea(IBS-D). Methods: A randomized, double-blind, double-dummy, and positive paral el control ed clinical trial was conducted from October 2014 to March 2016. Total y 342 patients from 13 clinical centers were enrolled and randomly assigned(at the ratio of 1:1) to a treatment group(171 cases) and a control group(171 cases) by a random coding table. The patients in the treatment group were administered oral y with TXNG(5 g per time) combined with pinaverium bromide Tablet simulator(50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator(5 g per time) combined with pinaverium bromide Tablets(50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score(IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief(AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire(IBS-QOL), Hamilton Anxiety Scale(HAMA), Hamilton Depression Scale(HAMD), and the recurrence rate at fol ow-ups. Safety indices including the adverse events(AEs) and related laboratory tests were evaluated. Results: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set(FAS) and per protocol set(PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group(147/171, 86.0%) was higher than the control group(143/171, 83.6%) by FAS(P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups(P>0.05). The recurrence rate at 8-week fol ow-up was 12.35%(10/18) in treatment group and 15.79%(12/76) in control group, respectivery(P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups(P>0.05). Conclusion: Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide.(No. ChiCTR-IPR-15006415)

感染后肠易激综合征肠道菌群及血清代谢物对内脏敏感性影响

目的:探讨感染后肠易激综合征(PI-IBS)小鼠肠道菌群与血清代谢物的变化,分析其对内脏敏感性的影响。方法:采用旋毛虫感染法制备PI-IBS模型,利用16S rDNA测序分析PI-IBS小鼠和正常小鼠肠道微生物变化;血清代谢组学分析血清代谢物变化;Spearman法对2组的差异代谢物和差异菌群进行关联分析。结果:16S rDNA测序结果显示mouse gut metagenome和g_Alistipes可能是PI-IBS小鼠的关键肠道微生物。代谢组学分析共筛选出22种组间差异代谢物,涉及16条代谢通路,主要包括氨基酸的生物合成、半胱氨酸和蛋氨酸代谢、精氨酸生物合成、突触囊泡循环等通路。结论:肠道菌群和血清代谢物改变参与PI-IBS内脏高敏感性的产生。

Irritable Bowel Syndrome:Common Integrative Medicine Perspectives

Previous reviews have highlighted complementary and alternative medicine therapies that are used to treat irritable bowel syndrome（IBS） based on published clinical trial data.Here the author describes and comments on a number of potentially relevant factors that have been commonly emphasized by practitioners who treat IBS and patients who have the disease.They include gluten and other food allergies,the Candida syndrome and biofilm,interference fields and post-infectious IBS, as well as mind-body factors.

基于中西医临床特点的感染后肠易激综合征动物模型分析

目的 基于感染后肠易激综合征的中西医临床诊断标准及症状特点,对现有的感染后肠易激综合征动物模型进行总结归纳及模型评价,以期寻找中西医临床吻合度高的动物模型,为感染后肠易激综合征的中医药防治提供精准动物模型。方法 通过查阅整理感染后肠易激综合征动物实验及其动物模型制备相关文献,基于感染后肠易激综合征的临床诊断特点及症状特征,将现有感染后肠易激综合征动物模型的动物品系、造模方法及机制进行归纳总结,并进行吻合度评价、分析模型制备的优缺点。结果 综合评价后发现,中西医临床吻合度相对较高的是空肠弯曲杆菌感染模型、旋毛虫感染模型以及病症结合模型中的肝郁脾虚证模型。结论 现有的感染后肠易激综合征模型普遍西医吻合度高于中医吻合度,造模过程中普遍对中医四诊及证候的体现及信息收集较少,中医诊断中的主症主要依靠观察动物表观行为,而对次症表现的观察则相对较少,导致中医证型的判断欠准确。因此,仍需进一步规范病证结合动物模型的症状评价标准和辨证方法。具备中西医临床病证特点的感染后肠易激综合征动物模型在未来具有较大的应用价值及应用前景,采用西医病理损伤+中医病因刺激的多因素复合方法造模可建立吻合度更高的感染后肠易激综合征模型,可为研究感染后肠易激综合征发病机制、证候差异、中西医结合防治提供理论支持,对指导感染后肠易激综合征的临床诊断和治疗具有重要意义。

中医药治疗感染后肠易激综合征的研究进展

感染后肠易激综合征(post-infectious irritablebowel syndrome,PI-IBS)是肠易激综合征的一个亚型,发生于急性肠道感染恢复后。中医药治疗PI-IBS有明确疗效,具有依从性高、费用少的特点。文章通过梳理中医药治疗PIIBS的报道,从病因病机、治疗方法两方面对中医药治疗PI-IBS进行综述。

感染后肠易激综合征肠屏障功能损伤的研究进展

肠易激综合征(irritable bowel syndrome,IBS)是常见的功能性胃肠病,具体的发病机制尚未能阐明。感染后肠易激综合征(post-infectious irritable bowel syndrome,PI-IBS)是其中的一个亚型。肠黏膜屏障由机械屏障、免疫屏障、化学屏障、生物屏障4个部分组成,在维持肠道稳态发挥至关重要的作用。肠黏膜屏障受损和许多疾病相关,而这一病理改变在PI-IBS中客观存在。肠屏障功能损伤机制与PI-IBS的关系有待进一步研究。文章主要从PI-IBS相关的屏障损伤的机制进行概述,为深入研究和可能的临床应用提供帮助。

Extra-intestinal and long term consequences of Giardia duodenalis infections

Giardiasis is the most common waterborne parasitic infection of the human intestine worldwide.The etiological agent,Giardia duodenalis(syn.G.intestinalis,G.lamblia),is a flagellated,binucleated protozoan parasite which infects a wide array of mammalian hosts.Human giardiasis is a true cosmopolitan pathogen,with highest prevalence in developing countries.Giardiasis can present with a broad range of clinical manifestations from asymptomatic,to acute or chronic diarrheal disease associated with abdominal pain and nausea.Most infections are self-limiting,although re-infection and chronic infection can occur.Recent evidence indicating that Giardia may cause chronic post-infectious gastrointestinal complications have made it a topic of intense research.The causes of the post-infectious clinical manifestations due to Giardia,even after complete elimination of the parasite,remain obscure.This review offers a state-of-the-art discussion on the long-term consequences of Giardia infections,from extra-intestinal manifestations,growth and cognitive deficiencies,to post-infectious irritable bowel syndrome.The discussion also sheds light on some of the novel mechanisms recently implicated in the production of these postinfectious manifestations.

APETx2对感染后肠易激综合征小鼠内脏敏感性的作用及机制

目的探讨酸敏感离子通道3特异性拮抗剂(APETx2)对感染后肠易激综合征(PI-IBS)小鼠内脏敏感性的调控作用及其机制。方法采用旋毛虫感染NIH小鼠建立PI-IBS模型。通过测量首次排黑便的时间和6 h内收集的粪便颗粒数评估胃肠道运输功能;腹壁回撤反射(AWR)评分评估小鼠内脏敏感性;免疫组织化学法检测结肠组织中降钙素基因相关肽(CGRP)蛋白表达;通过实时定量PCR(qRT-PCR)法检测结肠组织中脑源性神经营养因子(BDNF)、CGRP mRNA表达。蛋白质印迹法(Western blot)检测脑组织中酸敏感离子通道3(ASIC3)、CGRP、瞬时受体电位香草素1(TRPV1)蛋白表达。结果与对照组比较,PI-IBS组首次排黑便时间显著降低,6 h内的粪便颗粒数,AWR评分均显著升高,结肠组织中CGRP蛋白表达显著升高,BDNF、CGRP mRNA显著升高,脑组织中CGRP、ASIC3、TRPV1的蛋白表达显著升高;与PI-IBS组比较,APETx2组首次排黑便时间显著延长,6 h内的粪便颗粒数,AWR评分均显著降低,结肠组织中CGRP蛋白表达显著降低,BDNF、CGRP mRNA表达显著降低,脑组织中CGRP、ASIC3、TRPV1的蛋白表达显著降低,差异均有统计学意义(P<0.05)。结论APETx2可通过下调BDNF、CGRP、ASIC3、TRPV1的表达,减轻PI-IBS小鼠的内脏敏感性并调节胃肠道运动。APETx2可能为治疗IBS提供一个新的治疗选择。

感染后肠易激综合征小鼠肠黏膜和血中细胞因子的表达变化

【目的】观察感染后肠易激综合征小鼠不同肠段和外周血中IFN-γ、IL-17、IL-10的表达及以上细胞因子的改变对肠道动力和内脏敏感性的影响。【方法】40只雌性C57BL\6小鼠随机分为PI-IBS组和对照组,每组20只。PI-IBS组小鼠用0.2 m L含350条旋毛虫幼虫的生理盐水悬液灌胃,对照组给予等体积的生理盐水。分别于感染后第2、4、8周,取末端回肠和近端结肠进行组织病理学检测。于感染后第8周通过检测小鼠腹壁撤退反射(AWR)评分评估小鼠对结直肠扩张的内脏敏感性变化,检测肠道传输时间(ITT)和粪便含水百分数评估小鼠肠道动力的改变;采用ELISA测定十二指肠、空肠、回肠、结肠和外周血中IFN-γ、IL-17和IL-10水平的改变。【结果】感染后第8周,PI-IBS小鼠肠道急性炎症完全恢复至正常;在结直肠扩张容量为0.35和0.5 m L时,模型组AWR评分均显著高于对照组(P<0.01);PI-IBS小鼠肠道传输时间缩短、每2 h粪便含水百分数增高,较正常对照组具有显著性差异(P<0.01);ELISA结果显示:与对照组相比,PI-IBS组小鼠的IFN-γ和IL-17水平在十二指肠、回肠和外周血中表达升高(P<0.05);而IL-10水平在空肠、回肠、结肠以及外周血中的表达显著降低(P<0.05)。【结论】感染后肠易激综合征小鼠不同肠段组织中细胞因子表达水平存在差异,外周血与部分肠段组织中细胞因子的表达变化呈同步化改变。细胞因子的改变可能是PI-IBS内脏敏感性增高和肠道运动功能紊乱的机制之一。

戊己丸不同配伍方对炎症后肠易激综合征模型大鼠结肠运动及5-羟色胺含量的影响

目的:评价戊己丸不同配伍方对炎症后肠易激综合征(post-infectious irritable bowelsyndrome,PI-IBS)模型大鼠结肠运动功能的作用,并从5-羟色胺(5-hydroxytryptamine,5-HT)角度初步探讨其作用机制.方法:采用乙酸灌肠加束缚应激建立PI-IBS大鼠模型,应用戊己丸不同配伍方进行干预,应用BIOPAC MP150型多导生理记录仪描记大鼠结肠运动曲线,计算结肠运动指数和运动指数变化率,同时利用高效液相法检测血清、结肠、海马、下丘脑和额叶中5-HT的含量及5-HT转化率,甲苯胺蓝染色法计算结肠肥大细胞数目和脱颗粒率.结果:经戊己丸治疗后,中、高剂量组PI-IBS模型大鼠结肠运动指数(1770.10、1504.97、1700.64、1467.22 vs 2112.15)和运动指数变化率(68.10、40.16、59.97、39.33 vs 104.69)均显著下降(P<0.01).结肠组织中5-HT含量显著下降(3493.38、2640.41、2086.08、3255.63、2688.69、2129.13 vs 4168.36),血清中5-HT转化率(3.20、4.60、6.61、2.86、3.40、4.05 vs2.08)明显升高(P<0.05,P<0.01).中、高剂量组中枢边缘系统中5-HT含量(243.16、295.03、250.28、303.61 vs 124.42;303.51、397.30、339.94、353.02 vs 198.58;260.87、302.75、254.65、298.92 vs 166.71)显著升高(P<0.01),5-HT转化率(134.69、98.61、130.57、95.87vs 281.91;209.43、184.55、189.56、186.75vs 262.01;109.36、86.52、115.41、88.47 vs268.36)明显下降(P<0.05,P<0.01).结肠黏膜肥大细胞数目(6.40、5.11、6.48、5.57 vs 10.47)和脱颗粒率(23.81、17.94、23.25、19.19 vs34.10)亦明显下降(P<0.01).结论:戊己丸不同配伍方改善PI-IBS模型大鼠结肠运动功能的作用机制可能是通过改善5-HT含量及肥大细胞的异常状态,从而调节脑-肠轴功能实现的.

感染后内脏高敏感小鼠肠道黏膜固有层树突细胞对CD4^+T 细胞的作用

背景：多项证据提示感染后肠易激综合征（PI-IBS）患者的肠道黏膜中存在T细胞介导的低度炎症.树突细胞（DC）是肠道黏膜免疫系统中最重要的抗原呈递细胞,目前关于DC在PI-IBS中作用的报道尚少.目的：研究肠道黏膜固有层DC在急性肠道感染的不同阶段对CD4＋T细胞的影响,探讨DC在肠道感染消退后维持肠道黏膜免疫系统持续激活中的作用.方法：建立旋毛虫感染后内脏高敏感小鼠模型以模拟人类PI-IBS.肠道黏膜固有层DC与脾脏CD4＋T细胞于体外共培养120 h,ELISA法检测细胞培养上清液中Th17、Th2、Th1相关细胞因子IL-17、IL-4、IFN-γ水平.结果：与单独培养相比,CD4＋T细胞与DC共培养后,感染后8周组IL-17水平增加值明显高于对照组（P=0.001）和感染后2周组（P=0.279）：感染后2周组IL-4水平增加值明显高于对照组（P=0.041）和感染后8周组（P=0.204） 三组间IFN-γ水平增加值差异均无统计学意义.结论：感染后内脏高敏感小鼠肠道黏膜固有层DC诱导CD4＋T细胞分化为Th17细胞并使之活化可能是肠道感染消退后维持肠道黏膜免疫系统持续激活的主要机制.