Journal Article

Integrated Multi‐Omic Analysis Identifies Altered Colonic Brush Border Profile as a Key Feature of Microscopic Colitis

Vicario, Maria, Guagnozzi, Danila, Zabana, Yamile, Exposito, Elba, Lucendo, Alfredo J., Fernández‐Bañares, Fernando, Llerena‐Castro, Ronald, Sidorova, Julia, Benages, Ana, Santos, Javier, Gonzalez‐Castro, Ana Maria, Münch, Andreas, Dot, Joan, Lobo, Beatriz, Tristan, Eva, Alonso‐Cotoner, Carmen, Lozano, Juan‐José, Castillo Cejas, Maria Dolores, Landolfi, Stefania

2026

Overview

Background Microscopic colitis (MC), comprising lymphocytic colitis (LC) and collagenous colitis (CC), is an inflammatory bowel disease with increasing incidence. MC etiopathogenesis remains unknown; however, altered colonic epithelial integrity may underlie uncontrolled luminal antigen passage, triggering immuno‐inflammatory responses. Objective The aim of this study was to further define the involvement of the colonic epithelium in MC. Methods A paired transcriptomic and proteomic analysis followed by epithelial ultrastructural examination was performed on colonic biopsies from LC and CC patients, and from irritable bowel syndrome with a predominance of diarrhoea (IBS‐D) and healthy subjects (H) as control groups. The impact of budesonide therapy on the epithelial structure was also evaluated in CC. Results MC patients exhibited decreased expression of inter‐microvilli adhesion and actin‐bundling proteins, accompanied by increased expression of actin‐membrane connection proteins compared to both control groups. Distinct molecular differentiated CC and LC, which translated into differential ultrastructure abnormalities. The colonic microvilli in CC patients were shorter in length and fewer in number, with partial restoration following budesonide treatment, whereas LC showed a reduction solely in microvilli number. A negative correlation was found between daily stool frequency and SPATN1 and ATP8B1 protein levels in CC patients. Conclusions Molecular dysregulation and aberrant ultrastructure of the colonic brush border feature the colonic epithelium in LC and CC. These previously undescribed findings provide new perspectives for further defining MC pathogenesis and identifying biomarkers for diagnosis, prognosis and treatment of this debilitating and prevalent disease. Key Summary Summarise the established knowledge on this subject ◦ Microscopic colitis (MC) is a chronic immune‐mediated disease characterized by colonic mucosal inflammation and barrier dysfunction, but a deeper characterization of colonocytes is lacking. What are the significant and/or new findings of this study? ◦ This study is the first to MC identify molecular and ultrastructural alterations of the brush border in colonocytes in lymphocytic colitis (LC) and collagenous colitis (CC). ◦ The uniqueness of this study relies on the identification of a molecular phenotype of the brush border that differentiates from healthy controls and, notably, from the closest diarrhoeal disorder, irritable bowel syndrome with a predominance of diarrhoea. ◦ Given the fundamental role of the brush border in maintaining intestinal homoeostasis and regulating epithelial barrier function, our study sets the basis for the identification of new predictive diagnostic and/or prognostic biomarkers for both LC and CC, as well as new potential therapeutic targets.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Adult / Aged / Biopsy / brush border / Budesonide - pharmacology / Budesonide - therapeutic use / Case-Control Studies / Colitis, Collagenous - drug therapy / Colitis, Collagenous - genetics / Colitis, Collagenous - immunology / Colitis, Collagenous - pathology / Colitis, Lymphocytic - drug therapy / Colitis, Lymphocytic - genetics / Colitis, Lymphocytic - immunology / Colitis, Lymphocytic - pathology / Colitis, Microscopic - drug therapy / Colitis, Microscopic - genetics / Colitis, Microscopic - pathology / collagenous colitis / Colon - drug effects / Colon - immunology / Colon - pathology / Colon - ultrastructure / Female / Gene Expression Profiling / Humans / Inflammatory bowel disease / Intestinal Mucosa - drug effects / Intestinal Mucosa - immunology / Intestinal Mucosa - metabolism / Intestinal Mucosa - pathology / Intestinal Mucosa - ultrastructure / Irritable bowel syndrome / Irritable Bowel Syndrome - drug therapy / Irritable Bowel Syndrome - pathology / Luminal / lymphocytic colitis / Male / microscopic colitis / microvilli / Microvilli - drug effects / Microvilli - metabolism / Microvilli - pathology / Microvilli - ultrastructure / Middle Aged / Multiomics / Original / Proteomics - methods / Transcriptome