Table 1.
Proposed possible pathogenic mechanisms of MC
| Proposed pathogenesis of MC | Altered components | Specific changes | Influencing factor | Mechanism description | Comments | References |
|---|---|---|---|---|---|---|
| Environmental factors | Smoking and alcohol consumption | Smoking: alteration of the gut microbiome, and inflammation induction; alcohol consumption: integrity of the intestinal epithelial barrier; endotoxin-producing bacteria | NA | Smoking: epithelial barrier dysfunction and intestinal inflammation; alcohol consumption: increasing the trans-epithelial and paracellular passage of luminal antigens, dysbiosis, and intestinal bacterial overgrowth | Smoking: a pooled OR of 2.99 for current smokers and 1.63 for former smokers compared with never smokers; alcohol consumption: aHRs of MC were 1.20 for consumers of 0.1–4.9 g/day of alcohol, 1.90 for consumers of 5–14.9 g/day, and 2.31 for consumers of ≥15 g/day | [15, 16] |
| Medication | PPIs, NSAIDs, statins, and SSRIs | Intraluminal environment and bacterial flora; bowel integrity and colonic permeability | NA | PPIs: acid suppression-related colonic dysbiosis and affected immune reaction; NSAIDs: intestinal damage and increased bile salt cytotoxicity; statins: unknown; SSRIs: aggravation of colitis symptoms by interference with the gastrointestinal motility and secretion | Poor understanding of the pathogenic mechanisms | [17–20] |
| Infectious agents | Clostridioides difficile, norovirus, Escherichia species, Campylobacter concisus, and H. pylori | Enteric flora; intestinal microenvironment | NA | Further dysbiosis of the enteric flora; intestinal epithelial sodium channel dysfunction and claudin-8-dependent gut barrier dysfunction; alteration of the intestinal microenvironment activates the immune pathway | H. pylori may reduce the risk of MC and the “hygiene hypothesis” may be the relevant mechanism. | [11, 12, 22–26] |
| Autoimmune disorders | HLA haplotypes; autoantibodies; hypersensitivity response | Concomitant autoimmune conditions and shared HLA genotype; serum antinuclear antibodies, IgM, antigliadin IgA, anti-endomysial, ASCA; drug or food allergy | Some drugs | Underlying autoimmune diseases affecting the gut or cross-reactivity of antigens due to increased intestinal permeability | No direct evidence | [10] |
| Genetic factors | Genetic predisposition | HLA region and the extended haplotype 8.1 | NA | HLA-DQ2 as a shared genetic predisposition to celiac disease; haplotype 8.1 in association with collagenous colitis | HLA regions play a role in MC | [10] |
aHR, adjusted hazard ratio; ASCA, anti-Saccharomyces cerevisiae antibody; HLA, human leukocyte antigen; H. pylori, Helicobacter pylori; MC, microscopic colitis; NA, not available; NSAIDs, non-steroidal anti-inflammatory drugs; OR, odds ratio; PPIs, proton-pump inhibitors; SSRIs, selective serotonin reuptake inhibitors.