Dissecting Microscopic Colitis Immunopathophysiology: Insights From Basic Research

Abstract

Microscopic colitis is an inflammatory bowel disease (IBD) comprising two clinically undiscernible entities: collagenous colitis and lymphocytic colitis. Collagenous colitis associates with HLA genes and displays a Th1/Tc1–Th17/Tc17 profile with pericryptal myofibroblast activity, water malabsorption and secondary fluid loss due to altered osmoregulation. Conversely, lymphocytic colitis lacks genetic associations and displays a Th1/Th2 profile and paracellular/transcellular permeability. Lymphocytic colitis subclassifies into channelopathic lymphocytic colitis due to unique alteration of ion and organic acid transport that could result from drug exposure, and inflammatory lymphocytic colitis due to the involvement of moderate immune responses compared to collagenous colitis. As microscopic colitis mucosa remains intact and immune cells seem to stay inactive, microscopic colitis is an ideal model to explore early stages of IBD if collagenous colitis and lymphocytic colitis are studied as distinct entities. Exploiting multiomic approaches and established biobanks will ensure validation of microscopic colitis patient stratification, and deepening into pathomechanisms which could enable precision medicine.