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).

An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide.

Background and aim: Microscopic colitis (MC) is an inflammatory disease of the bowel, hypothetically induced by an immunologic response to a luminal microbial agent. We aimed to characterize the microbiome composition in MC and subtypes collagenous colitis (CC) and lymphocytic colitis (LC) and to identify a possible microbial effect of treatment. Method: Stool samples were collected from MC patients prior to treatment, at 8 weeks (during treatment) and at 16 weeks (after treatment), and from healthy controls, not receiving treatment, at matched time-points. Microbiome composition was analyzed by sequencing of the 16S and 18S genes. Differences between patients and controls were analyzed by Shannon's diversity index (mean, standard deviation (SD)) and principal coordinate analysis (PCoA) complemented with a permanova test of UniFrac distances. Results: Ten LC patients, 10 CC patients and 10 controls were included. By PCoA, the bacterial composition in MC patients differed from controls at baseline (p = .02), but not during and after treatment (p = .09 and p = .33, respectively). At baseline, bacterial diversity was lower in MC patients compared to controls (2.5, SD: 0.5 vs 3.5, SD: 0.3, p < .05). Diversity in MC patients increased during (3.0, SD: 0.6) and after treatment and (2.9, SD: 0.5) compared with baseline (p < .01). Eukaryotes were detected in fewer samples from MC patients compared with controls (11/20 (55%) vs. 9/10 (90%), p = .06) with no effect of treatment. Conclusion: Microbiome composition is altered in MC patients. During and after treatment with budesonide the microbiome composition in MC patients was driven towards the composition in healthy controls.

Advances in knowledge on microscopic colitis: from bench to bedside / Avance en el conocimiento de la colitis microscópica: desde el laboratorio a la cabecera de la cama

Microscopic colitis (MC) is a general term that describes a family of chronic inflammatory bowel diseases, including lymphocytic colitis (LC) and collagenous colitis (CC). The two forms are characterized by chronic watery diarrhea with normal or near normal endoscopic colonic appearance and specific histopathological abnormalities. Data from recent epidemiological studies reported the diagnosis of MC from several different regions in the world, providing that it can be a worldwide condition. The etiopathogenesis of MC still remains unknown but it is generally accepted that MC is a multifactorial disease, probably secondary to an abnormal immune reaction in predisposed individuals, triggered by different luminal factors (infections, drugs, autoimmunity and/or bile acids). Furthermore, some studies show that the epithelial barrier function in the colonic mucosa of MC patients is also impaired. Several mucosal factors of intestinal inflammation have been studied in MC, postulating that an aberrant T-lymphocyte response may lead to a chronic gut inflammatory condition, with the infiltration of colonic mucosa by different proportion of subset of T-lymphocytes. Little is known about the specific inflammatory mediators in MC pathogenesis, but a predominant Th1 type cytokine profile has been demonstrated. Currently, a number of medical treatments have been studied in MC patients, following mainly an empirical treatment approach. Further studies are needed in order to obtain prospective and more evidence-based data. In the future, it will be possible to develop causal treatment approaches after better understanding the molecular mechanisms behind the origin of the disease

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Gastroduodenal mucosa in microscopic colitis.

BACKGROUND: We have assessed gastroduodenal, endoscopical and histopathological findings in a series of patients with microscopic colitis (MC). METHODS: We studied 75 patients with MC, 27 with collagenous colitis (CC) and 48 with lymphocytic colitis (LC), and 60 controls. Data of endoscopical findings were collected and biopsies were assessed. RESULTS: Helicobacter pylori infection rate was 15% in MC and 28% in the controls (p = 0.088). Age at diagnosis of MC was higher in H. pylori positive than negative patients (63.4 ± 9.6 vs. 54.4 ± 13.1 years; p = 0.034). Gastric endoscopic erosions were more prevalent in CC than in LC (25.9% vs. 6.2%; p = 0.030) and associated with thick body glands and antral predominance of gastritis in H. pylori positive patients. Rates of focal gastritis (5.6% vs. 6.9%) and lymphocytic gastritis (5.6% vs. 10%) were similar in MC and controls. LC was associated with gastric epithelial lymphocytosis and lymphocytic gastritis. Fifteen patients (20%) had celiac disease. CONCLUSIONS: Unlike LC, CC is associated with endoscopic erosions, likely related with the high acid secretion capacity as indicated by the ample body glands and antral predominance of gastritis in H. pylori associated cases of CC. The presence of some divergent gastroduodenal features in LC and CC, and in comparison with those reported in inflammatory bowel disease (IBD), supports the concept that these two conditions differ not only from IBD but also from each other. The findings also suggest the presence of pathogenetic links between colorectal and gastroduodenal abnormalities.

Lymphocytic colitis: a clue to bacterial etiology.

AIM: To find out the role of bacteria as a possible etiological factor in lymphocytic colitis. METHODS: Twenty patients with histopathological diagnosis of lymphocytic colitis and 10 normal controls were included in this study. Colonoscopic biopsies were obtained from three sites (hepatic and splenic flexures and rectosigmoid region). Each biopsy was divided into two parts. A fresh part was incubated on special cultures for bacterial growth. The other part was used for the preparation of histologic tissue sections that were examined for the presence of bacteria with the help of Giemsa stain. RESULTS: Culture of tissue biopsies revealed bacterial growth in 18 out of 20 patients with lymphocytic colitis mostly Escherichia coli (14/18), which was found in all rectosigmoid specimens (14/14), but only in 8/14 and 6/14 of splenic and hepatic flexure specimens respectively. In two of these cases, E coli was associated with proteus. Proteus was found only in one case, Klebsiella in two cases, and Staphylococcus aureus in one case. In the control group, only 2 out of 10 controls showed the growth of E coli in their biopsy cultures. Histopathology showed rod-shaped bacilli in the tissue sections of 12 out of 14 cases with positive E coli in their specimen's culture. None of the controls showed these bacteria in histopathological sections. CONCLUSION: This preliminary study reports an association between E coli and lymphocytic colitis, based on histological and culture observations. Serotyping and molecular studies are in process to assess the role of E coli in the pathogenesis of lymphocytic colitis.