Henrik Hjortswang

Microscopic colitis (MC) is an inflammatory bowel disease characterized by chronic watery diarrhea. Although barrier dysfunction and immune activation are implicated, underlying mechanisms remain unclear. The aim of this study was to characterize enteric glial cells (EGC) and mast cell distribution across MC subtypes, assess treatment effects, and explore EGC-related gene expression and barrier markers. Colonic biopsies from patients with active collagenous colitis (aCC), budesonide-refractory CC (rCC), and active lymphocytic colitis (LC) were compared to irritable bowel syndrome (IBS), ulcerative colitis (UC), and healthy controls (HC). A subset of CC patients was studied during active disease (aCC) and in clinical remission due to budesonide treatment (tCC). Immunofluorescence quantified EGC positive for glial fibrillary acidic protein (EGC^GFAP+) and S100 calcium-binding protein B (EGC^S100β+), mast cell tryptase, and tight junction proteins. RNA-sequencing assessed EGC-related gene expression. Results showed that EGC^GFAP+ were highest in rCC and decreased following budesonide treatment in aCC, whereas EGC^S100β+ were highest in aCC, remained unchanged following treatment, resembled IBS, and were reduced compared with UC. Mast cell numbers were higher in aCC than in HC and rCC but remained unchanged following treatment, while mast cell degranulation decreased after treatment. Tight junction proteins were unchanged. RNA-sequencing indicated differential regulation of EGC-related genes. In conclusion, MC shows subtype-specific alterations involving EGC and mast cells, suggesting distinct glial states and differential treatment responsiveness. Our findings support the presence of distinct neuroimmune alterations in CC and LC and highlight EGC as potential contributors to MC pathophysiology.

Background: Acute infectious gastroenteritis (GE) and inflammatory bowel disease (IBD) may have similar clinical characteristics at onset, and discrimination between these two diagnoses can initially be challenging. Aim: To explore faecal biomarkers reflecting neutrophil, eosinophil, and epithelial activity to distinguish between acute GE and IBD onset. Methods: Faecal samples were collected from patients presenting with acute GE (n = 28), treatment-naïve patients with newly diagnosed IBD (n = 40), and healthy controls, HC (n = 40). Faecal biomarkers, including faecal calprotectin (FC), myeloperoxidase (MPO), human neutrophil lipocalin (HNL), eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN), were assessed by ELISA. The Kruskal–Wallis test was used for biomarker comparisons. To evaluate the discriminative capability of biomarkers, receiver operating characteristic (ROC) curves were established. Result: Patients with acute GE displayed elevated levels of all the tested biomarkers compared with HC (p < 0.001). Higher levels of faecal HNL (p < 0.001), EDN (p < 0.01), and MPO (p < 0.05) were seen in acute GE patients than in patients with newly diagnosed IBD. HNL yielded the highest discriminative capability between acute GE and IBD with AUC 0.74, 95%CI: 0.62–0.84. Conclusions: This exploratory study suggests that faecal biomarkers may provide complementary information in the differentiation of patients with suspected acute GE and new-onset IBD. Our findings indicate that faecal HNL may have the ability to distinguish between these conditions. However, given the exploratory design and limited sample size, findings should be interpreted with caution, and the discriminative value of HNL and the other biomarkers requires further validation in larger, well-characterised acute GE cohorts.

INTRODUCTION: Fecal calprotectin (FC) is a noninvasive tool for examining response to biologics in inflammatory bowel disease (IBD), but its performance in relation to other novel fecal markers of various cellular origins is unknown. METHODS: We performed a prospective multicenter cohort study and included patients with active IBD who provided a fecal sample at initiation of biological therapy. Levels of FC, myeloperoxidase (MPO), human neutrophil lipocalin (HNL), and eosinophil-derived neurotoxin (EDN) were analyzed and related to clinical remission status at 3 months. Changes in levels of markers at 3 months were calculated, and the impact of concomitant use of corticosteroids at baseline was estimated. RESULTS: In patients achieving clinical remission (n = 27), a decrease in levels of FC (P = 0.005), MPO (P < 0.001), HNL (P < 0.001), and EDN (P < 0.001) was observed, whereas no significant decrease was seen in patients not achieving remission (n = 39). There was a significant difference in the change in the level of MPO (P = 0.01) and HNL (P = 0.02) between patients achieving clinical remission and those who did not, but changes in FC and EDN could not differentiate between these groups. Patients with concomitant systemic corticosteroids at inclusion had lower levels of HNL (P = 0.01) and EDN (P < 0.001) at baseline, compared with patients without corticosteroids. DISCUSSION: Fecal MPO, HNL, and EDN are all promising biomarkers for assessing the treatment outcome of biologics in patients with IBD. Fecal levels of EDN and HNL are significantly affected by corticosteroids indicating a greater sensitivity to the effects of corticosteroids compared with levels of FC and MPO.