Partial to complete abrogation of the subepithelial macrophage barrier against the gut microbiota in patients with ulcerative colitis and Crohn's colitis

摘要

Aims The integrity of the band of indigenous macrophages in the subepithelial layer of the lamina propria (SLP) is crucial in preventing the commensal gut microbiota from attacking the host. The breakdown of the SLP macrophage barrier results in microbiota inflow and improper immune responses; this might lead to inflammatory bowel disease (IBD). During inflammation, the SLP macrophage barrier is reinforced by inflammation‐elicited macrophages (IEMs), which are derived from blood‐circulating monocytes. The aim was to explore the characteristics of the SLP macrophage band in a cohort of biopsies without inflammation, in patients with ulcerative colitis in remission (UCre), and in patients with right‐sided Crohn's colitis (RCC). Methods and results Endoscopic biopsies were taken from endoscopically normal descending colon in 247 patients; 80 with IBD (27 UCre and 53 RCC), and 167 without IBD [90 had colonic diarrhoea, 63 were enrolled in a colorectal cancer (CRC) surveillance programme, seven had microscopic colitis in remission, and seven had miscellaneous colonic ailments]. Sections showed no inflammatory changes; they were immunostained with CD68. Among patients with UCre and RCC, the SLP band of CD68+ macrophages was fragmented or minute in 59% (47/80) and negative in 9% (7/80). In contrast, only 31% (51/167) of the biopsies from control patients had a fragmented/minute SLP band of CD68+ macrophages, and none had a negative SLP band of CD68+ macrophages (IBD versus controls, P ??0.05). Conclusions The finding that the SLP macrophage barrier was fragmented to totally abrogated in UCre and RCC patients suggests a longlasting defect in the SLP CD68+ macrophage barrier in these patients. The lack of ongoing inflammation in colonic biopsies should rule out the participation of bone marrow‐derived IEMs in the abrogation of the SLP macrophage barrier reported here.