Gastrointestinal Infection and Risk of Microscopic Colitis: A Nationwide Case-Control Study in Sweden.

BACKGROUND AND AIMS: Gastrointestinal infections have been linked to changes in the composition and function of gut microbiome and development of inflammatory bowel diseases. We therefore sought to examine the relationship between gastroenteritis and risk of microscopic colitis (MC). METHODS: We conducted a case-control study of all adult patients with MC diagnosed between 1990 and 2016 in Sweden matched to up to 5 general population controls according to age, sex, calendar year, and county. Cases of MC were identified using Systematized Nomenclature of Medicine codes from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, a cohort of gastrointestinal pathology reports from all 28 pathology centers in Sweden. We used logistic regression modeling to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Through December of 2016, we matched 13,468 MC cases to 64,479 controls. The prevalence of previous diagnosed gastrointestinal infection was 7.5% among patients with MC, which was significantly higher than in controls (3.0%, Pcomparison < .001). After adjustment, gastroenteritis was associated with an increased risk of MC (aOR 2.63; 95% CI 2.42-2.85). Among specific pathogens, Clostridioides difficile (aOR 4.39; 95% CI 3.42-5.63), Norovirus (aOR 2.87; 95% CI 1.66-4.87), and Escherichia species (aOR 3.82; 95% CI 1.22-11.58), but not Salmonella species, were associated with an increased risk of MC. The association between gastrointestinal infections and risk of MC was stronger for collagenous subtype (aOR 3.23; 95% CI 2.81-3.70) as compared with lymphocytic colitis (aOR 2.51; 95% CI 2.28-2.76; Pheterogeneity = .005). The associations remained significant after adjustment for immune-mediated conditions and polypharmacy and when compared with unaffected siblings. CONCLUSION: In a nationwide study, we found that gastrointestinal infection, particularly Clostridioides difficile, is associated with an increased risk of subsequent MC. This study was approved by the Regional Ethics Committee, Stockholm, Sweden (Protocol no. 2014/1287-31/4).

High risk of microscopic colitis after Campylobacter concisus infection: population-based cohort study.

OBJECTIVE: Microscopic colitis (MC) encompasses the two histopathological distinct entities of collagenous colitis (CC) and lymphocytic colitis (LC). In this Danish population-based cohort study, we examined the risk of MC following stool culture with Campylobacter concisus, C. jejuni, non-typhoidal Salmonella or a culture-negative stool test. DESIGN: We identified patients with a first-time positive stool culture with C. concisus, C. jejuni, non-typhoidal Salmonella or negative stool test, from 2009 through 2013 in North Denmark Region, Denmark, and matched each with 10 population comparisons. All subjects were followed up until 1 March 2018 using Systematised Nomenclature of Medicine codes from The Danish Pathology Register for incident diagnoses of CC and LC. We computed risk and adjusted HRs with 95% CIs for MC among patients and comparisons. RESULTS: We identified 962 patients with C. concisus, 1725 with C. jejuni, 446 with Salmonella and 11 825 patients with culture-negative stools. The MC risk and HR versus comparisons were high for patients with C. concisus (risk 6.2%, HR 32.4 (95% CI 18.9 to 55.6)), less for C. jejuni (risk 0.6%, HR 3.7 (95% CI 1.8 to 7.7)), low for Salmonella (risk 0.4%, HR 2.2 (95% CI 0.5 to 10.8)) and for patients with negative stool testing (risk 3.3%, HR 19.6 (95% CI 16.4 to 23.4)). After exclusion of the first year of follow-up, the HRs were 9.3 (95% CI 4.1 to 20.1), 2.2 (95% CI 0.9 to 5.4), 1.3 (95% CI 0.2 to 11.1) and 5.6 (95% CI 4.6 to 7.2), respectively. CONCLUSION: A high risk of MC was observed following C. concisus in stools. Further studies are needed to elucidate any underlying biological mechanisms.

Proinflammatory Sulfur-Reducing Bacteria Are More Abundant in Colonic Biopsies of Patients with Microscopic Colitis Compared to Healthy Controls.

BACKGROUND: Microscopic colitis (MC), a subtype of inflammatory bowel disease, is a chronic condition of unknown etiology. Recent evidence has linked MC with intriguing changes in the stool microbiota, which may be linked to disease pathogenesis. The composition of the mucosal microbiome in patients with MC remains unclear. METHODS: We performed a cross-sectional study comparing colonic tissue samples from patients with MC to those of healthy controls at the Michael E. DeBakey VA Medical Center. We included adults older than 18 who underwent a colonoscopy with biopsies to evaluate chronic diarrhea. Cases were defined by histology consistent with MC and controls by the absence of histologic disease. We conducted structured chart review to exclude other gastrointestinal diseases and obtain demographic (age, sex, race) and clinical (duration of symptoms and concurrent medications) information for cases and controls. We extracted bacterial DNA from formalin-fixed paraffin-embedded tissue samples and sequenced the v4 region of the 16S rRNA gene. Operational taxonomic unit (OTU) clustering was performed using UPARSE, and OTUs were assigned using the SILVA database. Statistical analysis was performed in QIIME and LEfSe. Comparisons with FDR-adjusted p values of less than 0.05 were considered statistically significant. RESULTS: We included 20 MC patients and 20 controls with mean ages of 62 and 54, respectively. Most cases were White (95%), 60% had symptoms for greater than 12 months, and 50% were taking PPIs and NSAIDs at the time of their diagnosis. Compared to controls, MC patients had a significant increase in the proinflammatory sulfur-reducing bacterial family Desulfovibrionales. The Coriobacteriaceae family, abundant in the healthy gut, was significantly decreased in MC cases. There was also an increase in the genus Actinomyces in MC patients on PPI and an increase in the class Bacilli among those taking NSAIDs. DISCUSSION: Patients with MC have an increase in the proinflammatory family Desulfovibrionales. Actinomyces and Bacilli were associated with medications (PPI and NSAID) known to increase the risk of MC. Our findings may have important implications for understanding the pathogenesis of MC.

Anti-Yersinia antibodies are not associated with microscopic colitis in an American case-control study.

BACKGROUND: Microscopic colitis (MC), which consists of lymphocytic colitis and collagenous colitis, may be triggered by gastrointestinal infections. Studies have suggested a relationship between MC and Yersinia enterocolitica infection. We tested this hypothesis in a case-control study of American patients with MC. METHODS: Serum was collected from 47 patients with MC and 44 age- and gender-matched healthy controls at a large referral center in the mid-western United States. Anti-IgA and IgG antibodies to Y. enterocolitica were measured using an enzyme-linked immunosorbent assay (ELISA). Fisher's exact test was used to assess statistical significance. RESULTS: There were no differences between the two groups for seroprevalence of anti-Yersinia IgA (cases 2.1%, controls 2.3%, p = 1.00) or IgG antibodies (cases 4.3%, controls 6.8%, p = 0.67). There was no correlation between antibody titers and duration of MC diagnosis. CONCLUSION: Our data do not support the role of exposure to Y. enterocolitica in an American group of patients with MC.

Inverse Association Between Helicobacter pylori Gastritis and Microscopic Colitis.

BACKGROUND: Inflammatory bowel disease is known to be inversely associated with Helicobacter pylori infection of the upper gastrointestinal tract. We hypothesized that a similar inverse association also applied to microscopic colitis. METHODS: The associations between microscopic colitis and presence of H. pylori-positive chronic active gastritis (CAG), H. pylori-negative CAG, intestinal metaplasia, or gastric atrophy were expressed as odds ratios with their 95% confidence intervals. Multivariate logistic regression analyses were used to adjust these associations for sex, age, percentage residents per ZIP code with white, black, Hispanic, or Asian ethnicity, percentage with college education, average housing values, annual income, and population size of individual ZIP codes. RESULTS: H. pylori-positive CAG was less common among patients with than without microscopic colitis (odds ratio = 0.61; 95% confidence interval, 0.52-0.70). Intestinal metaplasia also occurred less frequently among patients with than without microscopic colitis (0.75, 0.65-0.86). These inverse associations remained unaffected by adjustments for parameters of ethnicity and socioeconomic status. In contradistinction with H. pylori-positive CAG, H. pylori-negative CAG was more common in patients with than without microscopic colitis (1.54, 1.17-1.97). CONCLUSIONS: H. pylori infection and microscopic colitis are inversely associated. This observation is consistent with similar inverse associations found between H. pylori and inflammatory bowel disease. These relationships may provide clues about the yet unknown etiology of microscopic colitis.

Microscopic colitis and small intestinal bacterial overgrowth--diagnosis behind the irritable bowel syndrome?

UNLABELLED: Some patients previously diagnosed with irritable bowel syndrome (IBS) may develop microscopic colitis or small intestinal bacterial overgrowth (SIBO). AIM: To estimate the prevalence of microscopic colitis and SIBO in patients with IBS, to evaluate the symptoms and the efficacy of treatment. MATERIAL AND METHODS: We examined patients with IBS admitted in our clinic during a three-year period. We identified patients with microscopic colitis by performing total colonoscopy with multiple biopsies from normal intestinal mucosa and those with SIBO by performing a H2-breath test with glucose. We compared the symptoms and the effectiveness of the treatment. RESULTS: Out of the 132 patients initially diagnosed with IBS 3% (n=4) had microscopic colitis and 43.9% (n=58) had SIBO. Diarrhea was the main symptom in patients with microscopic colitis and SIBO (p=0.041), while abdominal pain, abdominal bloating and flatulence were prominent in IBS patients (p=0.042; p=0.039; p=0.048). Specific treatment with rifaximin in SIBO patients negativated H2-breath test in 70.9% cases. CONCLUSIONS: Patients suspected to have irritable bowel syndrome should be evaluated for microscopic colitis and SIBO. The proper diagnosis and the specific treatment may cure some difficult cases of the so called "irritable bowel syndrome".