Post-infectious functional gastrointestinal disorders: from the acute episode to chronicity

Functional gastrointestinal disorders (FGID) form a major part of gastroenterology practice. Several studies have reported the development of post-infectious irritable bowel syndrome (PI-IBS) after acute gastroenteritis (AGE). Non-gastrointestinal (GI) infections may increase the risk of developing IBS. There are also data showing that a GI infection may trigger functional dyspepsia (PI-FD). The possible development of PI-IBS or PI-FD depends on factors related to both the infection and the host. Microinflammation has been found in patients with post-infectious FGID. Studies performed in animal models show that infection and acute inflammation permanently change gastrointestinal motility and sensitivity. The role of AGE in the development of FGID is important not only because this entity provides an excellent natural model for pathogenic study but also because it provides an opportunity for preventive action.     

Postinfection Irritable Bowel Syndrome

Following acute gastroenteritis (AGE) due to bacteria, viruses, or protozoa, a subset of patients develop new onset Rome criteria positive irritable bowel syndrome (IBS), called postinfection IBS (PI-IBS). The pooled prevalence of PI-IBS following AGE was 11.5%. PI-IBS is the best natural model that suggests that a subset of patients with IBS may have an organic basis. Several factors are associated with a greater risk of development of PI-IBS following AGE including female sex, younger age, smoking, severity of AGE, abdominal pain, bleeding per rectum, treatment with antibiotics, anxiety, depression, somatization, neuroticism, recent adverse life events, hypochondriasis, extroversion, negative illness beliefs, history of stress, sleep disturbance, and family history of functional gastrointestinal disorders (FGIDs), currently called disorder of gut-brain interaction. Most patients with PI-IBS present with either diarrhea-predominant IBS or the mixed subtype of IBS, and overlap with other FGIDs, such as functional dyspepsia is common. The drugs used to treat non-constipation IBS may also be useful in PI-IBS treatment. Since randomized controlled trials on the efficacy of drugs to treat PI-IBS are rare, more studies are needed on this issue.     

Relationship between infectious gastroenteritis and irritable bowel syndrome

A newly recognized causative factor in a subset of patients with irritable bowel syndrome (IBS) is called post-infectious IBS (PI-IBS). IBS symptoms frequently develop after an acute episode of infectious gastroenteritis. Several studies have been made in our understanding of the concept of PI-IBS. Recent studies suggest that transient or chronic gastrointestinal inflammation may play a role in IBS pathogenesis. PI-IBS can be regarded as a natural experiment model in which an insult in the form of an infective disease impacts on subjects with underlying genetic and psychosocial predispositions who then develop IBS. IBS is likely to be a complex trait wherein variability in clinical presentation is partially explained by heterogeneity in underlying genetic and environmental risk factors for PI-IBS. Further studies on PI-IBS are needed to understand the pathophysiology of functional gastrointestinal disorders and to develop new promising management for such patients.     

感染后肠易激综合征研究现状

肠易激综合征（IBS）是最常见的功能性胃肠病之一,已有研究证据表明其可能是多种因素共同作用的结果,包括遗传和环境因素、胃肠动力改变、内脏高敏感、肠道感染和炎症、慢性应激、肠道细菌过度生长和脑-肠轴功能紊乱等。部分患者在急性肠道感染恢复后仍存在腹痛、腹部不适、腹泻等症状,即感染后肠易激综合征（PI-IBS）,是近年功能性胃肠病的研究热点。本文就PI-IBS的定义、流行病学、发病机制、动物模型、临床特征、诊断和治疗等研究现状作一概述。     

急性胃肠道感染相关功能性消化不良的初步研究

目的 调查急性胃肠道感染相关功能性消化不良(PI-FD)的临床特点,初步探讨其可能的发生机制.方法 对原先无消化道症状的550例急性胃肠道感染患者随访半年,评估PI-FD的发生率及其症状特点,同时收集30例非特异性功能性消化不良(NS-FD)和20例健康志愿者,测定其胃黏膜肥大细胞(MC)的数量和活化水平;测定胃黏膜MC的分泌介质类胰蛋白酶含量和组胺释放量;电镜观察MC的状态及其与神经纤维的毗邻关系.结果 550例急性胃肠道感染患者中28例失访,随访6个月时功能性消化不良(FD)发生率为6.7%(35/522);PI-FD组的上腹痛、烧灼感和早饱的症状积分高于NS-FD组(P值均<0.05),PI-FD组和NS-FD组的MC计数均显著高于健康对照组(P值均<0.05),其中PI-FD组患者激活状态的MC数量显著高于Ns-FD组(P<0.05);同时,PI-FD组患者胃黏膜类胰蛋白酶含量和组胺释放量均显著高于NS-FD组和健康对照组(P值均<0.05);在PI-FD患者,电镜下观察到距神经纤维5μm范围内的MC数量显著高于其他两组(P值均<0.05).结论 PI-FD可能是一种特殊类型的FD,临床症状以反复发作的上腹痛、烧灼感和早饱为主,MC可能参与了PI-FD的发病过程.     

Post-infectious irritable bowel syndrome

Irritable bowel syndrome (IBS) affects 8% to 22% of the general population. Although patients describe an insidious onset of symptoms, including abdominal pain relieved with bowel movements, excessive intestinal gas, variable bowel habits, and abdominal bloating, a subgroup of individuals describe the onset of IBS symptoms following an episode of acute gastroenteritis, known as post-infectious IBS (PI-IBS). Several studies have demonstrated the development of IBS following infection. Risk factors for the development of PI-IBS are female sex and longer duration of initial illness. Although the underlying mechanism of PI-IBS is unclear, ongoing inflammation is clearly a factor in the pathogenesis. The underlying inflammatory process results in increased enterochromaffin cells, T-lymphocytes, intestinal permeability, colonic transit time, and a variety of immunologic abnormalities. PI-IBS patients tend to have a better prognosis than do those with idiopathic IBS, with resolution of symptoms within 5 to 6 years. Treatment is similar to that of idiopathic IBS.     

The functional-organic dichotomy: postinfectious irritable bowel syndrome and inflammatory bowel disease-irritable bowel syndrome

Gastroenterologists often encounter situations when the clinical and pathophysiological features that typically distinguish functional from organic disorders overlap. This "blurring of boundaries" can occur with post-infectious irritable bowel syndrome (PI-IBS), a subset of IBS and a newly described entity IBD-IBS. The key associating features include pain and usually diarrheal symptoms that are disproportionate to the observed pathology, microscopic inflammation, and often a co-association with psychological distress. A previous initiating gastrointestinal infection is required for PI-IBS and assumed for IBD-IBS. Using this perspective we discuss the clinical and pathophysiological features of PI-IBS and IBD-IBS and the growing evidence for the overlapping features of these two disorders in terms of alteration of gut flora, immune dysregulation, and role of stress. A unifying model of PI-IBS and IBD-IBS is proposed that may have important clinical and research implications. It obligates us to reframe our understanding of illness and disease from the dualistic biomedical model into a more integrated biopsychosocial (BPS) perspective.     

感染后功能性消化不良患者胃黏膜肠嗜铬细胞的改变

背景：已证实肠嗜铬细胞（EC细胞）在感染后肠易激综合征（PI-IBS）的发生中起重要作用。功能性消化不良（FD）与IBS同属功能性胃肠病范畴,推测感染后FD（PI-FD）与PI-IBS可能存在相似的发病机制。目的：观察PI-FD患者胃黏膜EC细胞数量、功能的改变,初步探讨PI-FD的可能发生机制。方法：纳入35例PI-FD患者、30例非PI-FD患者和20名健康志愿者。35例PI-FD患者中,14例粪便培养致病菌阳性（PI-FD-A组）,21例粪便培养阴性,根据临床表现确诊（PI-FD-B组）。以5-羟色胺（5-HT）免疫组化染色计数胃黏膜EC细胞,高效液相色谱电化学法检测胃黏膜5-HT浓度,透射电子显微镜观察EC细胞超微结构及其与神经纤维的毗邻关系。结果：PI-FD组胃黏膜EC细胞数和5-HT浓度显著高于非PI-FD组和健康对照组（P〈0.05）,且EC细胞数量与黏膜炎症程度呈正相关（P〈0.05）。电子显微镜下,EC细胞内细胞器较多,部分胞质内可见特异性分泌颗粒,PI-FD组距神经纤维5μm范围内EC细胞数显著高于非PI-FD组和健康对照组（P〈0.05）。PI-FD-A组与PI-FD-B组的EC细胞数量和5-HT浓度均无明显差异。结论：PI-FD患者胃黏膜EC细胞显著增殖、活化,EC细胞激活途径可能在PI-FD的发病过程中起重要作用。     

Acute and Chronic Histological Changes of the Small Bowel Secondary to <Emphasis Type="Italic">C. jejuni</Emphasis> Infection in a Rat Model for Post-Infectious IBS

Background  

Campylobacter jejuni has been implicated in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS) in humans, effects which may be because of cytolethal distending toxin (CDT). In this study, we characterized both acute and chronic-phase histological changes of the small bowel in rats exposed to wild-type C. jejuni 81-176, or a strain that does not produce CDT, by using a validated rat model of PI-IBS.     

Almost all irritable bowel syndromes are post-infectious and respond to probiotics: controversial issues

Acute infectious gastroenteritis is the strongest known risk factor for the development of irritable bowel syndrome (IBS), one of the most common functional gastrointestinal disorders. However, knowledge about the incidence and prevalence of post-infectious IBS (PI-IBS) in the general population is still limited. Some of the published epidemiological studies on PI-IBS lack an appropriate control population, and were limited by a short follow-up symptom assessment post-infection. A number of risk factors have been associated with the development of PI-IBS, including the virulence of the pathogen, younger age, female sex, the long duration of the initial illness and the presence of psychological disturbances. However, much work has to be done to establish whether multifactorial mechanisms actually concur to the pathophysiology of PI-IBS. The discovery that an infective episode may trigger the development of IBS has not substantially changed the clinical management of this subset of patients compared to the classical (non-infective) form of IBS. Probiotics have been claimed to be of some benefit in IBS, but the majority of studies have been performed in non-specific IBS rather than in PI-IBS and a number of issues still remain to be elucidated.     

Travel and Travelers�� Diarrhea in Patients with Irritable Bowel Syndrome

This study evaluated occurrence of travel and travelers’ diarrhea in patients with irritable bowel syndrome (IBS). A survey was mailed to 591 patients of a clinical practice who had IBS. Based on survey responses, patients were categorized as having IBS, post-infectious IBS (PI-IBS), unclassified functional bowel disorder (UFBD), or post-infectious UFBD (PI-UFBD). Of 201 persons who returned questionnaires meeting inclusion criteria, 57.7%, 11.4%, 24.9%, and 6.0% had IBS, UFBD, PI-IBS, and PI-UFBD, respectively. Travel during six months before illness onset was more common in patients with PI-IBS or PI-UFBD than in persons with idiopathic IBS or UFBD (P = 0.006). Survey results demonstrated that 16.1% of post-infectious bowel disorder cases and 7.5% of overall IBS cases in a general medical population developed chronic disease within six months of an international trip. Symptoms of established functional bowel disorder in each clinical category were shown to worsen after travel-related acute diarrhea.     

Irritable bowel syndrome and inflammatory bowel disease: infectious gastroenteritis-related disorders?

Infectious gastroenteritis may be one of the important factors in the development of irritable bowel syndrome (IBS), with affected individuals often categorized as having post-infectious IBS (PI-IBS), and is linked to the onset of symptoms in approximately 10–20% of patients diagnosed with IBS. Intestinal mucosal infiltration of T cells and mast cells, and enterochromaffin cell hyperplasia are significant immunological and pathological findings that reveal the pathogenesis of PI-IBS, and results of laboratory studies using animal models of PI-IBS clearly support clinical evidence. Recently, infectious gastroenteritis has also been suggested to be associated with the development of inflammatory bowel disease (IBD), and various studies have suggested that individuals with IBS or IBS-like symptoms may be susceptible to initiation of IBD. However, it is still unclear whether infectious gastroenteritis is directly or indirectly (through PI-IBS) linked to the initiation of IBD. Additional studies are necessary to understand the clinical overlap among infectious gastroenteritis, IBS, and IBD.     

Post-infectious irritable bowel syndrome in patients with Shigella infection

BACKGROUND AND AIMS: Bacterial gastroenteritis has been known as a risk factor of irritable bowel syndrome (IBS). Several risk factors of post-infectious IBS (PI-IBS) have been documented. The aims of this study were to verify the role of bacterial gastroenteritis in the development of IBS and the risk factors for the development of PI-IBS. The clinical course of PI-IBS was also investigated. METHODS: We recruited 143 patients with shigellosis during its outbreak and 113 controls. Both groups were followed up for 12 months. Bowel symptoms were evaluated by use of questionnaires at 3, 6 and 12 months after the initial recruitment. RESULTS: Complete data were obtained from 101 patients (70.6%) and 102 healthy controls (90.3%). At 12 months, 15 patients and six controls had IBS (adjusted OR; 2.9, 95% CI; 1.1-7.9). Of the 15 patients, five had IBS symptoms consistently for 12 months, three did not have IBS symptoms initially and seven had fluctuating bowel symptoms. The duration of diarrhea was an independent risk factor of PI-IBS. CONCLUSIONS: Bacterial gastroenteritis is a risk factor of IBS and the duration of diarrhea as the index of severity of initial illness is an independent risk factor of PI-IBS. The clinical course of PI-IBS is variable over the 1 year of follow-up.     

The development of irritable bowel syndrome after Shigella infection: 3 year follow-up study]

BACKGROUND/AIMS: Bacterial gastroenteritis seems to be a risk factor of irritable bowel syndrome (IBS). The incidence of post-infectious IBS (PI-IBS) was reported to be in the range of 7-31%, but few studies have reported long term follow-up results. So, we investigated the clinical course and prognosis of PI-IBS three years after shigella infection. METHODS: The subjects were recruited from our previous study, in which we investigated the incidence and risk factors of PI-IBS. We had a questionnaire based on interview with 120 controls and 124 patients who had shigella infection three years ago. Both groups were evaluated for the presence of IBS, functional bowel disorders (FBD) except IBS before, one and three years after the infection, respectively. RESULTS: Ninety-five patients (76.6%) and 105 controls (87.5%) completed the questionnaire. In patients group, 7 cases had IBS prior to infection (previous IBS), 12 cases (13.8%) had IBS after 1 year (PI-IBS). Four cases developed IBS newly after 3 years (new IBS). Thirteen cases (14.9%) in patients and 4 cases (4.5%) in controls had IBS over 3 years (OR 3.93: 1.20-12.86). The recovery rate over 3 years were 50.0% (2/4) in previous IBS and 25% (3/12) in PI-IBS. The incidence of PI-IBS after 3 years in previous FBD subjects was 28.6% and was 10.6% in normals (p<0.05). The female gender was a risk factor for FBD. CONCLUSIONS: Bacterial gastroenteritis is a trigger factor of IBS. About a quarter of PI-IBS patients are recovered over 3 years. Previous FBD except IBS is a risk factor after 3 years.     

The Traveling Microbiome

Given the recent interest in the human gut microbiome in health and disease, we have undertaken a review of the role of the gut microbiome as it relates to travel. Considering the microbiome as the interface with the external world of the traveler, not only from the perspective of protection from enteric infection by colonization resistance but also the possibility that a traveler’s unique microbiome may place him or her at lesser or greater risk for enteric infection. We review available data on travel, travelers’ diarrhea, and the use of antibiotics as it relates to changes in the microbiome and the acquisition of multi-drug-resistant bacteria and explore the interplay of these factors in the development of dysbiosis and the post-infectious sequelae of TD, specifically PI-IBS. In addition, we explore whether dietary changes in travel affect the gut microbiome in a way which modulates gastrointestinal function and susceptibility to infection and discuss whether pre- or probiotics have any meaningful role in prevention or treatment of TD. Finally, a discussion of important research gaps and opportunities in this area is identified.     

Factors associated with the development of post-infectious functional gastrointestinal diseases: does smoking play a role?

OBJECTIVES: Irritable bowel syndrome (IBS) is associated with psychological stress, alterations in gut motor function and/or visceral perception. Previous studies suggest 7-32% of people develop IBS after bacterial gastroenteritis but the exact mechanisms underlying post-infectious IBS are not clear. The present study's aim was to examine the role of possible causative factors in the development of post-infectious functional gastro-intestinal disorders (FGIDs), including IBS. METHODS: A prospective cohort study where 122 people without a prior FGID under study and with stool-positive bacterial gastroenteritis consented to participate. The presence or not of IBS, functional dyspepsia or functional diarrhoea was diagnosed at the start and on 6-month follow-up using self-complete Rome II modular questionnaires. Demographic data, smoking, alcohol use, anxiety and depression (using the Hospital Anxiety and Depression Scale), and life events and impact (using the Life Events Survey) were collected at the start of the study. RESULTS: One hundred and seven questionnaires were returned with 25 participants (23.4%) developing a FGID and 16 participants presenting symptoms consistent with IBS (15%). Smoking was significantly associated with the development of a post-infectious FGID (odds ratio = 4.8, 95% confidence interval = 1.5-15.2) on regression analysis. CONCLUSIONS: Post-infectious FGIDs appear to be associated with smoking. Smoking is known to moderate gut immunity in other disorders such as ulcerative colitis and Crohn's disease. This study adds to increasing evidence for an organic basis to post-infectious FGIDs, perhaps moderated via inflammatory pathways.     

Systematic review with meta-analyses: does the pathogen matter in post-infectious irritable bowel syndrome?

Objective: Acute gastroenteritis (AGE) is a risk factor for post-infectious irritable bowel syndrome (PI-IBS). This systematic review evaluates the prevalence and risk-factors of PI-IBS after AGE by specific pathogens.

Materials and methods: Medline (1966–2019) and Embase (1974–2019) were searched for studies evaluating PI-IBS minimum 3 months after AGE with Campylobacter spp., Salmonella spp., Shigella spp., Escherischia coli, Clostridium difficile, norovirus, rotavirus, Cryptosporidium spp. or Giardia intestinalis using validated criteria for IBS. Pooled prevalence (PP), odds ratios (OR) and risk factors were determined for single pathogens, groups of bacteria, viruses and parasites, and overall for AGE caused by any pathogen. Random-effect models were used for meta-analyses.

Results: A total of 34 articles were included. PP of PI-IBS after Campylobacter spp. was 12% (confidence interval 95% [CI]: 10–15%), Salmonellosis 12% (CI: 9–15%), Shigellosis 11% (CI: 8–15%), C. difficile 14% (CI: 4–29%) and E. coli spp. 12% (CI: 5–20%). OR of PI-IBS after salmonellosis was 5.5 (CI: 2.3–12.8) and after shigellosis 13.8 (CI: 4.2–45.4). Bacterial AGE overall showed OR 5.8 (CI: 4.0–8.3) and AGE caused by any pathogen OR 4.9 (CI: 3.9–6.1). Few studies exist on viral and parasitic gastroenteritis.

Conclusions: Current literature show similar risks for bacterial pathogens. Studies are limited for viral and parasitic pathogens. The evaluated risk-factors for PI-IBS varied among the included studies and the existing evidence is insufficient to identify pathogen-specific risk factors.     

Microbial signatures in post-infectious irritable bowel syndrome – toward patient stratification for improved diagnostics and treatment

Irritable bowel syndrome (IBS) is a multifactorial and heterogeneous disorder estimated to affect over 10% of the Western population. A subset of the patients reports the start of the disease after an episode of gastroenteritis. The alterations in the intestinal microbiota of the post-infectious IBS (PI-IBS) patients were recently investigated in a British cohort and shown to differentiate from the healthy controls and resemble that of diarrhea-predominant IBS (IBS-D) patients. The altered 27 genus-like groups created a microbial signature, which could be used to objectively stratify patients and healthy controls. In this addendum, we combine the microbiota data derived from the British cohort with that of a recently reported Swedish PI-IBS cohort. Remarkably, robust and reproducible microbiota signatures were observed in these PI-IBS patients. We discuss these results with attention on the emerging role of microbiota in the classification, development and treatment of PI-IBS.     

Efficacy of Probiotics and Nutrients in Functional Gastrointestinal Disorders: A Preliminary Clinical Trial

The purpose of this study was to evaluate the efficacy and safety of commonly used probiotics and nutrients available for functional gastrointestinal disorders (FGID). Five different combinations of probiotics and nutrients, or placebo, were taken daily over 12 weeks. In this randomized controlled clinical trial, men and women 21 to 72 years of age with FGID symptoms of indigestion, bloating, and abdominal discomfort were assigned to one of six groups, 12 patients per group. Gastrointestinal Quality of Life Index (GIQLI) and visual analogue scale (VAS) for GI symptoms, SF-36, lactulose and mannitol test (LMT), and urine indican levels were evaluated. GIQLI, VAS scores, and LMT did not change significantly (P > 0.05). There were clinically notable improvements in two of the combination formulations. While the nonsignificant improvements in GI symptoms could suggest that combination probiotics and nutrients may be beneficial in conditions such as FGID, no conclusive evidence was found in this pilot trial. Further investigations to explore the findings are discussed.