Prevalence of irritable bowel syndrome and functional dyspepsia after acute gastroenteritis: systematic review and meta-analysis.

OBJECTIVE: Disorders of gut-brain interaction may arise after acute gastroenteritis. Data on the influence of pathogen type on the risk of postinfection IBS (PI-IBS), as on postinfection functional dyspepsia (PI-FD), are limited. We conducted a systematic review and meta-analysis to determine prevalence of PI-IBS or PI-FD after acute gastroenteritis. DESIGN: We included observational studies recruiting ≥50 adults and reporting prevalence of IBS or FD after acute gastroenteritis with ≥3-month follow-up. A random effects model was used to estimate prevalence and ORs with 95% CIs. RESULTS: In total, 47 studies (28 170 subjects) were eligible. Overall prevalence of PI-IBS and PI-FD were 14.5% and 12.7%, respectively. IBS persisted in 39.8% of subjects in the long-term (>5 years follow-up) after diagnosis. Individuals experiencing acute gastroenteritis had a significantly higher odds of IBS (OR 4.3) and FD (OR 3.0) than non-exposed controls. PI-IBS was most associated with parasites (prevalence 30.1%), but in only two studies, followed by bacteria (18.3%) and viruses (10.7%). In available studies, Campylobacter was associated with the highest PI-IBS prevalence (20.7%) whereas Proteobacteria and SARS-CoV-2 yielded the highest odds for PI-IBS (both OR 5.4). Prevalence of PI-FD was 10.0% for SARS-CoV-2 and 13.6% for bacteria (Enterobacteriaceae 19.4%). CONCLUSION: In a large systematic review and meta-analysis, 14.5% of individuals experiencing acute gastroenteritis developed PI-IBS and 12.7% PI-FD, with greater than fourfold increased odds for IBS and threefold for FD. Proinflammatory microbes, including Proteobacteria and subcategories, and SARS-CoV-2, may be associated with the development of PI-IBS and PI-FD.

A case of infective colitis due to Yersinia enterocolitica complicated by microliver abscesses mimicking multiple liver occult metastases: a case report.

BACKGROUND: We report an unusual case of infective colitis by Yersinia enterocolitica complicated by microliver abscesses mimicking multiple liver metastases in a 79 yr old female without any risk factors for bacteriaemia by this pathogen. CASE PRESENTATION: The patient was admitted to the Internal Medicine with Stroke Care ward of University Policlinico "P. Giaccone" in Palermo because of the appearance of diarrhoea. After the antimicrobial treatment for infective colitis, the clinicians observed a persistently increased white blood cells (WBC) count and multiple hepatic lesions; after having excluded any neoplastic disease and inflammatory bowel disease (IBD), blood cultures positive for Y. enterocolitica allowed to establish the final diagnosis was infective micro liver abscesses consequent to infective colitis due to Y. enterocolitica, which were successfully treated with cefixime and doxycycline. CONCLUSIONS: This case report should make clinicians reflect on how complex the differential diagnosis between microliver abscesses and metastasis could be and the possibility of bacteriaemia by Y. enterocolitica even without iron overload conditions.

Follow-on RifAximin for the Prevention of recurrence following standard treatment of Infection with Clostridium Difficile (RAPID): a randomised placebo controlled trial.

BACKGROUND: Clostridium difficile infection (CDI) recurs after initial treatment in approximately one in four patients. A single-centre pilot study suggested that this could be reduced using 'follow-on' rifaximin treatment. We aimed to assess the efficacy of rifaximin treatment in preventing recurrence. METHODS: A multisite, parallel group, randomised, placebo controlled trial recruiting patients aged ≥18 years immediately after resolution of CDI through treatment with metronidazole or vancomycin. Participants received either rifaximin 400 mg three times a day for 2 weeks, reduced to 200 mg three times a day for a further 2 weeks or identical placebo. The primary endpoint was recurrence of CDI within 12 weeks of trial entry. RESULTS: Between December 2012 and March 2016, 151 participants were randomised to either rifaximin or placebo. Primary outcome data were available on 130. Mean age was 71.9 years (SD 15.3). Recurrence within 12 weeks was 29.5% (18/61) among participants allocated to placebo compared with 15.9% (11/69) among those allocated to rifaximin, a difference between groups of 13.7% (95% CI -28.1% to 0.7%, p=0.06). The risk ratio was 0.54 (95% CI 0.28 to 1.05, p=0.07). During 6-month safety follow-up, nine participants died in each group (12%). Adverse event rates were similar between groups. CONCLUSION: While 'follow-on' rifaximin after CDI appeared to halve recurrence rate, we failed to reach our recruitment target in this group of frail elderly patients, so the estimated effect of rifaximin lacks precision. A meta-analysis including a previous trial suggests that rifaximin may be effective; however, further, larger confirmatory studies are needed.

Campylobacter jejuni promotes colorectal tumorigenesis through the action of cytolethal distending toxin.

OBJECTIVE: Campylobacter jejuni produces a genotoxin, cytolethal distending toxin (CDT), which has DNAse activity and causes DNA double-strand breaks. Although C. jejuni infection has been shown to promote intestinal inflammation, the impact of this bacterium on carcinogenesis has never been examined. DESIGN: Germ-free (GF) ApcMin/+ mice, fed with 1% dextran sulfate sodium, were used to test tumorigenesis potential of CDT-producing C. jejuni. Cells and enteroids were exposed to bacterial lysates to determine DNA damage capacity via γH2AX immunofluorescence, comet assay and cell cycle assay. To examine the interplay of CDT-producing C. jejuni, gut microbiome and host in tumorigenesis, colonic RNA-sequencing and faecal 16S rDNA sequencing were performed. Rapamycin was administrated to investigate the prevention of CDT-producing C. jejuni-induced tumorigenesis. RESULTS: GF ApcMin/+ mice colonised with human clinical isolate C. jejuni81-176 developed significantly more and larger tumours when compared with uninfected mice. C. jejuni with a mutated cdtB subunit, mutcdtB, attenuated C. jejuni-induced tumorigenesis in vivo and decreased DNA damage response in cells and enteroids. C. jejuni infection induced expression of hundreds of colonic genes, with 22 genes dependent on the presence of cdtB. The C. jejuni-infected group had a significantly different microbial gene expression profile compared with the mutcdtB group as shown by metatranscriptomic data, and different microbial communities as measured by 16S rDNA sequencing. Finally, rapamycin could diminish the tumorigenic capability of C. jejuni. CONCLUSION: Human clinical isolate C. jejuni 81-176 promotes colorectal cancer and induces changes in microbial composition and transcriptomic responses, a process dependent on CDT production.

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

Interest in the therapeutic potential of faecal microbiota transplant (FMT) has been increasing globally in recent years, particularly as a result of randomised studies in which it has been used as an intervention. The main focus of these studies has been the treatment of recurrent or refractory Clostridium difficile infection (CDI), but there is also an emerging evidence base regarding potential applications in non-CDI settings. The key clinical stakeholders for the provision and governance of FMT services in the UK have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. While the National Institute for Health and Care Excellence (NICE) guidance (2014) for use of FMT for recurrent or refractory CDI has become accepted in the UK, clear evidence-based UK guidelines for FMT have been lacking. This resulted in discussions between the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS), and a joint BSG/HIS FMT working group was established. This guideline document is the culmination of that joint dialogue.

A Mendelian Randomization Analysis Investigates Causal Associations between Inflammatory Bowel Diseases and Variable Risk Factors.

The question of whether variable risk factors and various nutrients are causally related to inflammatory bowel diseases (IBDs) has remained unanswered so far. Thus, this study investigated whether genetically predicted risk factors and nutrients play a function in the occurrence of inflammatory bowel diseases, including ulcerative colitis (UC), non-infective colitis (NIC), and Crohn's disease (CD), using Mendelian randomization (MR) analysis. Utilizing the data of genome-wide association studies (GWASs) with 37 exposure factors, we ran Mendelian randomization analyses based on up to 458,109 participants. Univariable and multivariable MR analyses were conducted to determine causal risk factors for IBD diseases. Genetic predisposition to smoking and appendectomy as well as vegetable and fruit intake, breastfeeding, n-3 PUFAs, n-6 PUFAs, vitamin D, total cholesterol, whole-body fat mass, and physical activity were related to the risk of UC (p < 0.05). The effect of lifestyle behaviors on UC was attenuated after correcting for appendectomy. Genetically driven smoking, alcohol consumption, appendectomy, tonsillectomy, blood calcium, tea intake, autoimmune diseases, type 2 diabetes, cesarean delivery, vitamin D deficiency, and antibiotic exposure increased the risk of CD (p < 0.05), while vegetable and fruit intake, breastfeeding, physical activity, blood zinc, and n-3 PUFAs decreased the risk of CD (p < 0.05). Appendectomy, antibiotics, physical activity, blood zinc, n-3 PUFAs, and vegetable fruit intake remained significant predictors in multivariable MR (p < 0.05). Besides smoking, breastfeeding, alcoholic drinks, vegetable and fruit intake, vitamin D, appendectomy, and n-3 PUFAs were associated with NIC (p < 0.05). Smoking, alcoholic drinks, vegetable and fruit intake, vitamin D, appendectomy, and n-3 PUFAs remained significant predictors in multivariable MR (p < 0.05). Our results provide new and comprehensive evidence demonstrating that there are approving causal effects of various risk factors on IBDs. These findings also supply some suggestions for the treatment and prevention of these diseases.

Rare case of EBV-induced colitis in an immunocompetent individual.

Epstein-Barr virus (EBV) is a member of the herpes virus family and affects people worldwide. EBV-infected colitis can occur in patients in immunocompromised states. However, EBV-induced colitis in immunocompetent patients is extremely rare. A 34-year-old man with a prior history of possible intussusception, and who underwent a right hemicolectomy, presented with abdominal pain and rectal bleeding. Laboratory investigations were unremarkable, and the patient underwent a colonoscopy, which showed EBV-infected colitis. Both infectious and inflammatory bowel disease (IBD) workups were negative. The patient's symptoms were resolved with supportive therapy. A repeat colonoscopy showed normal colonic mucosa with an absence of EBV infection. Without evidence of IBD or infectious aetiologies, EBV-associated colitis is a rare finding in an immunocompetent patient.

Development and validation of a simple and robust model to predict 30-day mortality in patients with Clostridioides difficile-associated enterocolitis.

OBJECTIVE: Clostridioides difficile infection (CDI) is a common healthcare-associated infection and associated with high morbidity and mortality. As current guidelines recommend treatment stratified for disease severity, this study aimed to identify predictors of 30-day mortality in order to develop a robust prediction model. DESIGN: This was a retrospective analysis of 207 inpatients with CDI who were treated at the Jena University Hospital between September 2011 and December 2015. In a training cohort (n=127), predictors of 30-day mortality were identified by receiver operating characteristics analysis and logistic regression. The derived model was validated in an independent cohort of 80 inpatients with CDI. RESULTS: Within 30 days, 35 (28%) patients in the training cohort died from any cause. C-reactive protein (CRP) of ≥121 mg/L (OR 3.80; 95% CI 1.64 to 7.80; p=0.003) and lower systolic blood pressure of ≤104 mm Hg (OR 3.73; 95% CI 1.63 to 8.53; p=0.002) at diagnosis as well as development of renal impairment (serum creatinine >1.5×baseline; OR 5.61; 95% CI 1.94 to 16.26; p=0.035) within the first 6 days were associated with 30-day mortality in univariate analysis. The use of these parameters enabled correct mortality prediction in 73% of cases on the day of diagnosis and in 76% at day 6. In the validation cohort, 30-day mortality was 18/80 (23%). Our model enabled a 73.7% correct prediction concerning 30-day mortality on day 6 after diagnosis of CDI. CONCLUSION: Hypotension and CRP elevation on the day of diagnosis as well as occurrence of kidney dysfunction during the first 6 days are suitable parameters to predict 30-day mortality in patients with CDI who need to be treated in the hospital.

Diagnostic dilemmas in chronic inflammatory bowel disease.

Histopathological assessment of biopsy and resection specimens of chronic inflammatory bowel disease (CIBD), or possible CIBD, forms a significant component of the routine workload in most tissue pathology laboratories. In this review, we have chosen selected areas of particular diagnostic difficulty in CIBD pathology, providing key advice for pathology reporting. Those mimics of CIBD which have the greatest potential for misdiagnosis are discussed, particularly the wide range of infectious colitides which represent possible diagnostic pitfalls. The most important distinguishing features between the two main forms of CIBD, ulcerative colitis and Crohn's disease, are addressed, first in relation to resection specimens, and then with emphasis on features which may also be diagnostically useful in endoscopic biopsy material. The importance of assessment of the index endoscopic specimen is stressed, before treatment has been instigated, along with careful correlation with clinical and endoscopic features. Problems in the assessment of post-surgical CIBD specimens are described and then the role of upper gastrointestinal pathology specimens in diagnosing both Crohn's disease and ulcerative colitis, with increased recognition of upper gastrointestinal tract involvement in the latter condition. Finally, with recent developments in endoscopic surveillance techniques and local excision options, modern approaches to reporting and managing neoplasia complicating CIBD are reviewed.

Mycobacterium avium subspecies hominissuis in Crohn's disease: a case report.

We have cultured Mycobacteria avium subspecies hominissuis (MAH) from the blood of a patient with Crohn's disease. The patient is a 21 year-old-female with a diagnosis of Crohn's disease for two years. She had been treated with corticosteroids and Humira for six months. A blood specimen was cultured in a specialized medium, and there was visible bacterial growth present in the liquid culture medium after eight weeks. PCR analysis of the bacterial growth and subsequent direct sequencing of the PCR amplicon confirmed the presence of MAH. The significance of this finding is discussed.

Colonic spirochetosis is associated with colonic eosinophilia and irritable bowel syndrome in a general population in Sweden.

Irritable bowel syndrome (IBS) is a functional disorder defined by symptoms in the absence of overt pathology. Colonic spirochetosis (CS), defined by histologic observation of spirochetal strains of Brachyspira in colonic biopsies, is uncommon and considered of doubtful significance. We aimed to determine the prevalence of CS in the general population, identify subtle colon pathologies, and evaluate a link with symptoms of IBS. Colonoscopy was performed in 745 subjects (aged 19-70 years, mean age 51 years, 43% male) with biopsies (ileum and 4 colonic sites) from a random population sample, Stockholm, Sweden, who completed a validated questionnaire of gastrointestinal symptoms; IBS was identified by Rome III criteria. CS was identified by histology and immunohistochemistry. In a general population, 17 individuals (2.28%; 95% confidence interval, 1.2%-3.5%) were diagnosed as having CS by histology; 6 (35%) had IBS. CS was always present in the sigmoid colon, but only 14 rectal biopsies. Eosinophils were increased in colon biopsies in CS cases versus controls, in the transverse (P = .02), sigmoid colon (P = .001), and rectum (P = .0005) with subepithelial eosinophil clusters (P = .053). Lymphoid follicles (at any site) were present in 13 CS (P = .0003). There was a 3-fold increased risk of IBS in CS (odds ratio, 3.59; 95% confidence interval, 1.27-10.11; P = .015). Polyps and diverticular disease were similar in CS cases and controls. The prevalence of CS in a general population is 2% and associated with nonconstipating IBS. Colonic eosinophilia with lymphoid follicles may signify the presence of CS.

Sexually transmitted infections manifesting as proctitis.

There is a rising incidence of several sexually transmitted infections (STIs), many of which can present with proctitis. Causative organisms include Neisseria gonorrhoeae, Chlamydia trachomatis, herpes simplex virus, Treponema pallidum (syphilis), Giardia lamblia (giardiasis) and Entamoeba histolytica (amoebiasis). This paper outlines important clinical discriminators and key investigations to distinguish these organisms from non-infective pathology that include inflammatory bowel disease, solitary rectal ulcer syndrome and Behçet's syndrome. Management of these infections is described and suggestions are made for successful gastroenterology clinical consultation when an STI is suspected.