肠易激综合征的治疗进展

肠易激综合征（irritable bowel syndrome,IBS）作为消化系统疾病中较为常见的功能性胃肠病,由于发病机制未 明,临床上缺乏行之有效的治疗手段,其临床诊治一直以来是研究的热点和难点。而近年来,相关药物的研发及诊疗 策略的更新,使得IBS的诊疗得到了进一步发展。文章就目前IBS的治疗进展做一论述,以期为IBS的临床诊治提供 指导,使更多的IBS患者从中获益。     

Rectal potential differences in irritable bowel syndrome and in inflammatory bowel diseases in man

We have studied rectal potential difference (pd) in 200 subjects: 30 healthy volunteers or control patients, 46 patients with irritable bowel syndrome (IBS) and painless diarrhoea (group I), 60 IBS patients without diarrhoea (group II) and 64 patients with inflammatory bowel disease (IBD) with (group III, n = 41) or without (group IV, n = 23) rectal involvement. Pd measurement used a rectal perfused probe and a subcutaneous needle both connected, via agar-KCl bridges, to calomel electrodes and a millivoltmeter. Statistical analysis used Student's t-test for paired and unpaired data and Mann-Whitney U-test as appropriate. Mean rectal pd values were, respectively -43.5 +/- 8.7 mV in control group, -32.9 +/- 10.2 mV in IBS-group I patients (P less than 0.001), -41.3 +/- 12 mV in IBS-group II patients (NS), -21.4 +/- 14.1 mV in IBD patients with rectal involvement (P less than 0.001), and -45.1 +/- 14.3 mV in IBD-group IV patients (NS). A histological examination was performed in 36 IBS patients; mean rectal pd was significantly decreased in patients showing abnormal patterns (n = 27, pd = -31.8 +/- 9 mV) compared to patients with normal mucosa (n = 9, pd = -41.1 +/- 6.5 mV; P less than 0.01). These results show that: (1) potential difference is significantly decreased in patients with ulcerative and rectal involvement; (2) in patients with Crohn's disease, normal rectal pd values do not assess the appearance of colonic mucosa above; (3) patients with IBS and diarrhoea also present a significant diminution in mean rectal pd. Although the mechanisms involved remain unclear, rectal pd measurement appears to be an objective test for intestinal mucosae weakness in functional or inflammatory diseases of the large intestine and rectum.     

The microbiome of the oral mucosa in irritable bowel syndrome

Irritable bowel syndrome (IBS) is a poorly understood disorder characterized by persistent symptoms, including visceral pain. Studies have demonstrated oral microbiome differences in inflammatory bowel diseases suggesting the potential of the oral microbiome in the study of non-oral conditions.

In this exploratory study we examine whether differences exist in the oral microbiome of IBS participants and healthy controls, and whether the oral microbiome relates to symptom severity.

The oral buccal mucosal microbiome of 38 participants was characterized using PhyloChip microarrays. The severity of visceral pain was assessed by orally administering a gastrointestinal test solution. Participants self-reported their induced visceral pain. Pain severity was highest in IBS participants (P = 0.0002), particularly IBS-overweight participants (P = 0.02), and was robustly correlated to the abundance of 60 OTUs, 4 genera, 5 families and 4 orders of bacteria (r² > 0.4, P < 0.001). IBS-overweight participants showed decreased richness in the phylum Bacteroidetes (P = 0.007) and the genus Bacillus (P = 0.008). Analysis of β-diversity found significant separation of the IBS-overweight group (P < 0.05). Our oral microbial results are concordant with described fecal and colonic microbiome-IBS and -weight associations. Having IBS and being overweight, rather than IBS-subtypes, was the most important factor in describing the severity of visceral pain and variation in the microbiome. Pain severity was strongly correlated to the abundance of many taxa, suggesting the potential of the oral microbiome in diagnosis and patient phenotyping. The oral microbiome has potential as a source of microbial information in IBS.     

Differences of microbiota in small bowel and faeces between irritable bowel syndrome patients and healthy subjects

Objective Several studies suggested that colonic microbiota have impacts on irritable bowel syndrome (IBS) patients. However, the knowledge about the association of small intestine (SI) microbiota with IBS is limited. We aimed to investigate the gut microbiota composition of SI and stool in IBS patients. Materials and methods Biopsies of jejunum mucosa by balloon-assisted enteroscopy and faecal samples from 28 IBS patients and 19 healthy controls were analysed by next-generation sequencing method. Results The three major phyla in SI microbiota of case/control groups were Proteobacteria (32.8/47.7%), Bacteroidetes (25.2/15.3%), and Firmicutes (19.8/11.2%), and those of stool were Bacteroidetes (41.3/45.8%), Firmicutes (40.7/38.2%), and Proteobacteria (15.4/7.1%). Analysis based on the family level, IBS patients had a higher proportion of Veillonellaceae (mean proportion 6.49% versus 2.68%, p?=?0.046) in stool than controls. Prevotellaceae was more abundant in IBS patients than in control group (14.27% versus 6.13%, p?=?0.023), while Mycobacteriaceae (0.06% versus 0.17%, p?=?0.024) and Neisseriaceae (6.40% versus 8.94%, p?=?0.038) was less abundant in IBS patients’ jejunal mucosa than those in controls. This less abundant jejunal Neisseriaceae was associated with more severe IBS (p?=?0.03). The ratio of Firmicutes to Bacteroidetes in the stool of IBS-diarrhoea type patients was approximately three-fold higher, and the ratio of Firmicutes to Actinobacter in SI of IBS-mixed type patients was about nine-fold higher than healthy subjects. Conclusion Higher abundance of colonic Veillonellaceae and SI Prevotellaceae, and lower amount of oral cavity normal flora in proximal SI were found in IBS patients. We may manipulate these bacteria in IBS patients in future studies (ClinicalTrial.gov Number NCT01679730).     

马来酸曲美布汀治疗肠易激综合征对比研究

目的探讨马来酸曲美布汀对肠易激综合征的治疗效果。方法将诊断为肠易激综合征（IBS）的97例患者随机分成试验组（47例）和对照组（50例），试验组给予马来酸曲美布汀，对照组使用复合维生素B作为安慰剂，两组疗程均为6周，治疗期间均停用其他药物，分别于治疗前及治疗的第2、4、6周及随访8、12周末进行症状评价及评分。结果试验组治疗后积分明显下降，治疗前后比较差异有非常显著性（P〈0．01）；对照组积分下降不明显，治疗前后比较差异无显著性（P〉0．05）；治疗4周后两组间比较，试验组积分下降较对照组明显，差异有非常显著性（P〈0．01）；治疗后两组疗效比较，试验组在2周后有效率达34％，8周和12周时分别达到83％和82％，疗效明显高于对照组，差异有非常显著性（P〈0．01）。结论马来酸曲美布汀对难治性功能性消化不良具有良好的治疗作用和安全性。     

Guidelines on the irritable bowel syndrome: mechanisms and practical management

Background

IBS affects 5–11% of the population of most countries. Prevalence peaks in the third and fourth decades, with a female predominance.

Aim

To provide a guide for the assessment and management of adult patients with irritable bowel syndrome.

Methods

Members of the Clinical Services Committee of The British Society of Gastroenterology were allocated particular areas to produce review documents. Literature searching included systematic searches using electronic databases such as Pubmed, EMBASE, MEDLINE, Web of Science, and Cochrane databases and extensive personal reference databases.

Results

Patients can usefully be classified by predominant bowel habit. Few investigations are needed except when diarrhoea is a prominent feature. Alarm features may warrant further investigation. Adverse psychological features and somatisation are often present. Ascertaining the patients'' concerns and explaining symptoms in simple terms improves outcome. IBS is a heterogeneous condition with a range of treatments, each of which benefits a small proportion of patients. Treatment of associated anxiety and depression often improves bowel and other symptoms. Randomised placebo controlled trials show benefit as follows: cognitive behavioural therapy and psychodynamic interpersonal therapy improve coping; hypnotherapy benefits global symptoms in otherwise refractory patients; antispasmodics and tricyclic antidepressants improve pain; ispaghula improves pain and bowel habit; 5‐HT₃ antagonists improve global symptoms, diarrhoea, and pain but may rarely cause unexplained colitis; 5‐HT₄ agonists improve global symptoms, constipation, and bloating; selective serotonin reuptake inhibitors improve global symptoms.

Conclusions

Better ways of identifying which patients will respond to specific treatments are urgently needed.     

A prospective assessment of bowel habit in irritable bowel syndrome in women: defining an alternator

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is subtyped as IBS with diarrhea (IBS-D) or IBS with constipation (IBS-C) based on Rome II guidelines. The remaining group is considered as having mixed IBS (IBS-M). There is no standard definition of an alternator (IBS-A), in which bowel habit changes over time. Our aim was to use Rome II criteria to prospectively assess change in bowel habit for more than 1 year to understand IBS-A. METHODS: Female patients (n=317) with IBS entering a National Institutes of Health treatment trial were studied at baseline with questionnaires and 2-week daily diary cards of pain and stool frequency and consistency. Studies were repeated at the end of treatment (3 months) and at four 3-month intervals for one more year. Algorithms to classify subjects into IBS-D, IBS-C, and IBS-M groups used diary card information and modified Rome II definitions. Changes in bowel habit at 3-month intervals were then assessed using these surrogate diary card measures. RESULTS: At baseline, 36% had IBS-D, 31% IBS-M, and 34% IBS-C. Except for stool frequency, there were no differences between groups. While the proportion of subjects in each subgroup remained the same over the year, most individuals (more than 75%) changed to either of the other 2 subtypes at least once. IBS-M was the least stable (50% changed out by 12 weeks). Patients were more likely to transition between IBS-M and IBS-C than between IBS-D and IBS-M. Notably, only 29% switched between the IBS-D and IBS-C subtypes over the year. CONCLUSIONS: While the proportion of subjects in each of the IBS subtypes stays the same, individuals commonly transition between subtypes, particularly between IBS-M and IBS-C. We recommend that IBS-A be defined as at least one change between IBS-D and IBS-C by Rome II criteria over a 1-year period.     

Efficacy of peripheral kappa agonist fedotozine versus placebo in treatment of irritable bowel syndrome

The efficacy and safety of the peripheral kappa agonist fedotozine was evaluated in a double-blind, multicenter study involving 238 patients with the irritable bowel syndrome. After a two-week washout, patients were assigned to one of four groups to receive either placebo or fedotozine three times a day at doses of 3.5, 15, or 30 mg for six weeks. Patient assessment of mean symptom intensity indicated that the 30-mg dose of fedotozine was superior to placebo in relieving maximal daily abdominal pain (P=0.01), mean daily pain (P=0.007), and abdominal bloating (P=0.02). Changes in bowel function and defecation disorders could not be evaluated reliably. According to the investigators, the highest dose of fedotozine markedly reduced overall disease severity (P=0.003) and the pain component of the symptomatic profile (P=0.009). Clinical and laboratory safety was very good. Fedotozine 30 mg three times a day therefore appears to be effective and safe in the treatment of the abdominal pain and bloating associated with IBS.Participating investigators: [France] Bataillon, Beaujard, Beranger, Boisson. Boboc, Bour, Bourry, Boyer, Cambon, Cassan, Chambon, Chery, Cosmidis, Dahlab, Dapoigny, Daudet, Debat, Delette. Delvaux, Desechalliers, Diez, Dumas, Faucher, Girard, Gislon, Hamelin, Hayek. Hecketsweiler, Joliot, Kornhauser, Lafon, Lamouliatte, Larche, Le Bihan, Legoux, Lirzin. Ljunggren, Marcheta, Marquier, Milon, Molinie, Monneris, Montoya, Morichau-Beauchant, Naudy, Pillegand, Raud Regeard, Renson, Richieri, Rouison, Rumeau, Salas, Staub, Vandermolen, Verbiese, Veyres, Wagner, Weber, Yousfi, Zani: [Tunisia] Ben Amar, Ben Kahlifa, Garoui, Hamza: [Belgium] Lamy, Lienard, Peeters.     

Gender-related differences in visceral perception in health and irritable bowel syndrome

BACKGROUND: Irritable bowel syndrome (IBS) is more common in female subjects, and IBS patients generally exhibit reduced pain thresholds to rectal distension. The aim of the present paper was to determine gender-related differences in rectal perception in both healthy controls and IBS patients. METHODS: Fifty-nine IBS patients (age 20-65 years; mean, 39.2 years; 31 women, 28 men) with symptoms that fulfilled Rome-II criteria and 21 healthy controls (age 25-58 years; mean, 37.8 years; 11 women, 10 men) were recruited. Participants completed a questionnaire regarding bowel symptoms and psychological distress, and maximal tolerable pressures were evaluated via barostat tests. RESULTS: Although healthy women appear to have lower perception thresholds than men, significant gender differences in pain sensitivity were not detected (P > 0.05). In addition, female patients with IBS also exhibited no enhanced colorectal perception, as compared with male IBS patients (P > 0.05). CONCLUSIONS: No gender differences in visceral perception were determined to exist between the healthy controls and the IBS patients. Therefore, the increased prevalence of IBS in women may be related to another set of pathophysiological factors, and not to gender-related differences in visceroperception.     

Association between body mass index and fecal calprotectin levels in children and adolescents with irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common pediatric functional gastrointestinal disorder. It is characterized by recurrent abdominal pain and changes in bowel habits and is more prevalent in obese patients. We investigated the association between obesity and IBS in pediatric patients through fecal calprotectin testing.Patients under 18 years of age with IBS who underwent fecal calprotectin testing from January 2015 through April 2020 were retrospectively investigated. The patients were divided into groups based on body mass index (BMI): group I (BMI < 85th percentile) and group II (BMI ≥ 85th percentile). Group II was divided into group IIa, overweight (85th percentile ≤ BMI < 95th percentile), and group IIb, obese (BMI ≥ 95th percentile).Among 277 included patients, 202 (72.9%) were in group I, and 75 (27.1%) were in group II (mean calprotectin levels, 75.60 ± 103.48 vs 45.89 ± 66.57 µg/g, respectively; P = .006). There were significant differences in mean calprotectin levels between groups I and IIa (75.60 ± 103.48 vs 45.45 ± 63.38 µg/g, respectively; P = .028) and groups I and IIb (75.60 ± 103.48 vs 46.22 ± 69.59 µg/g, respectively; P = .025). There was a significant difference in mean calprotectin levels between groups I and II (85.69 ± 142.13 vs 32.04 ± 28.17 µg/g, respectively; P = .029) among patients between 6 and 12 years of age but not among adolescents aged between 12 and 18 years (P = .139). Fecal calprotectin was lower when moderate-to-severe fatty livers were observed by ultrasound compared with normal livers (68.52 ± 97.22 vs 18.53 ± 18.56 µg/g, respectively; P = .017).Fecal calprotectin levels were higher in normal-weight pediatric IBS patients than in their obese counterparts, and this difference was more prominent in younger patients. In young children, IBS symptoms are thought to be influenced more by factors other than intestinal inflammation.     

Relationship of abdominal bloating to distention in irritable bowel syndrome and effect of bowel habit

BACKGROUND & AIMS: The relationship between the sensation of bloating, often ranked as the most bothersome symptom by patients with irritable bowel syndrome (IBS), and actual distention manifest as an increase in abdominal girth is controversial. Investigation of this problem has been hampered by the lack of a reliable ambulatory technique to measure abdominal girth. The aim of this study was to use the technique of abdominal inductance plethysmography to compare diurnal variation in girth in IBS patients and healthy volunteers, relating these changes to the sensation of bloating. METHODS: Abdominal girth was recorded for 24 hours in 20 IBS-constipation (age, 18-73 y), 20 IBS-diarrhea (age, 25-62 y) and 10 IBS-alternating (age, 21-59 y) female patients meeting Rome II criteria and 20 healthy female controls (age, 18-67 y). All subjects pursued normal daily activities, recording their symptoms of bloating and pain together with bowel habit. RESULTS: All patients with IBS, irrespective of bowel habit, reported significantly greater bloating than controls (P < .0001). Forty-eight percent of patients also showed distention beyond the 90% control range, with this being most prominent in IBS-constipation. Bloating correlated strongly only with distention in IBS-constipation (r > or = 0.48; P < or = .02). Neither bloating nor distention in IBS was related to body mass index, age, parity, or psychologic status. CONCLUSIONS: Abdominal distention is a clearly definable phenomenon in IBS that can reach 12 cm. However, it only occurs in half of patients reporting bloating, and the 2 only correlate in IBS-constipation. Bloating and distention may differ pathophysiologically and this appears to be reflected in the bowel habit subtype.     

消炎痛灌肠治疗粘液便型肠易激综合征

目的:研究消炎痛保留灌肠治疗粘液便型肠易激综合征(IBS)的疗效。方法:采用单盲及自身对照方法,应用消炎痛保留灌肠,治疗粘液便型IBS患者41例,并与庆大霉素 氢化考的松(31例)及氢化考的松 普鲁卡因(13例)两组进行比较。结果:消炎痛治疗10d使患者便次减少(P<0.05),粘液便消失(P<0.01),肠壁水肿消失(P<0.05),充血点消失(P<0.05),腹痛缓解(P<0.05)均显著优于另两组。消炎痛治疗3周复发率明显少于另2组(P<0.01)。结论:消炎痛保留灌肠治疗粘液便型IBS具有显著和近期疗效。     

抗抑郁药治疗肠易激综合征疗效荟萃分析及治疗适应证探讨

目的通过对抗抑郁药疗效的荟萃分析来探讨抗抑郁药治疗肠易激综合征(IBS)的适应证。方法检索MEDLINE、EMBASE和Cochrane对照研究登记库中IBS患者抗抑郁药治疗的随机对照研究(文献发表时间为2000-01-01-2018-03-31)。以成年IBS患者为研究人群,将抗抑郁药与安慰剂或常规治疗进行对比。以IBS的总体症状或腹痛症状无改善为结局指标,获得抗抑郁药治疗后IBS症状无改善的相对危险度(RR)和95%可信区间(CI),并根据危险差的倒数计算出所需要治疗的患者数(NNT)。对可能影响疗效的主要临床特征(即是否合并心理障碍、腹痛或腹部不适的严重程度、是否难治性IBS)和疗程进行亚组分析。结果纳入12项高质量的随机对照研究进行荟萃分析。与安慰剂或常规治疗相比,当合并抑郁或焦虑时,抗抑郁药治疗后IBS症状无改善的相对危险度是0.45(95%CI 0.26~0.80),NNT为3.7。在抑郁和焦虑未知组,难治性IBS患者抗抑郁药治疗后IBS症状无改善的相对危险度是0.58(95%CI 0.46~0.73),NNT为3.6;中-重度腹痛或腹部不适患者抗抑郁药治疗后IBS症状无改善的相对危险度是0.64(95%CI 0.44~0.93),NNT为4.7。抗抑郁药疗程≥3个月时,治疗后IBS症状无改善的相对危险度是0.66(95%CI0.54~0.81)。结论 IBS患者抗抑郁药治疗的适应证为合并抑郁或焦虑、难治性IBS、表现为中-重度腹痛或腹部不适的IBS患者;推荐疗程至少为3个月。     

Rifaximin for the treatment of diarrhea-predominant irritable bowel syndrome

Irritable bowel syndrome (IBS) is a chronic, functional bowel disorder characterized by abdominal pain or discomfort and altered bowel habit. The pathophysiology is unclear, but may include altered gut motility, visceral hypersensitivity, abnormal central pain processing, chronic low-grade intestinal inflammation, or disturbances in the gut microbiome. These etiological mechanisms, alongside environmental factors such as stress and anxiety, vary between individuals and represent potential targets for treatment. Rifaximin is a poorly absorbed oral antibiotic proposed to act on the gut microenvironment, used in the treatment of travelers’ diarrhea and hepatic encephalopathy. Clinical trials suggest the drug can reduce global IBS symptoms and improve bloating, abdominal pain, and stool consistency in some patients with non-constipated IBS, leading to Food and Drug Administration approval in the United States. This article considers the pharmacology of rifaximin, the evidence for its use in IBS, and the safety and tolerability of the drug.     

Effect of oral nicardipine on anorectal function in normal human volunteers and patients with irritable bowel syndrome

Paired controlled studies were performed in 10 normal volunteers and 32 patients with irritable bowel syndrome to investigate the effect of the calcium channel blocker nicardipine, on the responses of the anorectum to rectal distension and a meal. Nicardipine was administered orally in standard (20 mg) and sustained-release (30 mg twice a day) formulations. In normal volunteers standard nicardipine had no significant effect on the rectal responses to distension but did significantly reduce the postprandial motility index (P <0.05). In the patients with irritable bowel syndrome, standard nicardipine caused a significant reduction in distension-induced rectal motor activity (P <0.05) and increased the rectal sensory thresholds for desire to defecate and discomfort (P <0.02). Slow-release nicardipine caused a significant reduction in distension-induced activity (P <0.05) but did not alter rectal sensory thresholds. Both formulations of nicardipine significantly reduced the postprandial motility index (P <0.05) and symptoms (P <0.05). In conclusion, this study confirms that calcium channel blockers may be useful in the management of irritable bowel syndrome.     

The epidemiology of irritable bowel syndrome in a random population: prevalence,incidence, natural history and risk factors

Abstract. Objectives . The aim of the study was to assess prevalence, incidence, recovery, and risk factors of irritable bowel syndrome according to different definitions in a large random population. Design . A 5 year follow-up study of a sex- and age-stratified random sample of 4581 Danes interviewed about abdominal symptoms. Setting . The Glostrup Populations Studies Unit at Glostrup County Hospital. Main outcome measures . Prevalence, incidence, recovery, and the association of risk factors to irritable bowel syndrome (IBS). The percentage of subjects common to the populations selected by the various definitions of IBS. Results . According to various definitions, the prevalence of IBS varied from 5 to 65% and the incidence varied from 1 to 36%. At the 5 year follow-up only 5% of subjects with IBS were completely free of all symptoms. Psychological vulnerability and the experience of having problems were strongly associated with prevalence and incidence of IBS, whereas lifestyle factors only showed a very weak or no relationship to IBS. Populations defined as suffering from IBS according to the various definitions had less than 50% of the subjects in common. Conclusions . Irritable bowel syndrome is frequent but fluctuating in the general population. Psychological factors seem to be of greater aetiological importance to IBS than lifestyle factors. However, a generally accepted and precise definition is essential to make future studies comparable and to allow general conclusions to be drawn. Furthermore, it still needs to be verified whether the syndrome is a disease entity or just an acceptable, common life-condition.     

Effects of fecal microbiota transplantation in subjects with irritable bowel syndrome are mirrored by changes in gut microbiome

ABSTRACT

Irritable bowel syndrome (IBS) is a common disorder of the lower gastrointestinal tract. The pathophysiology is far from settled, but a gut microbial dysbiosis is hypothesized to be a contributing factor. We earlier published a randomized double-blind placebo-controlled clinical trial on fecal microbiota transplantation (FMT) for IBS – the REFIT trial. The present data set describes the engraftment and includes participants from the study who received active FMT; 14 participants with effect of FMT (Effect) and 8 without (No effect). Samples were collected at baseline, after 6 and 12 months. Samples from the transplants (Donor) served as a comparator. In total 66 recipient samples and 17 donor samples were subjected to deep metagenomic sequencing, and taxonomic and functional analyses were performed. Alpha diversity measures showed a significantly increased diversity and evenness in the IBS groups compared to the donors. Taxonomic profiles showed higher relative abundance of phylum Firmicutes, and lower relative abundance of phylum Bacteroidetes, compared to donors at baseline. This profile was shifted toward the donor profile following FMT. Imputed growth rates showed that the resulting growth pattern was a conglomerate of donor and recipient activity. Thirty-four functional subclasses showed distinct differences between baseline samples and donors, most of which were shifted toward a donor-like profile after FMT. All of these changes were less pronounced in the No effect group. We conclude that FMT induces long-term changes in gut microbiota, and these changes mirror the clinical effect of the treatment. The study was registered in ClinicalTrials.gov (NCT02154867).