Linking bacterial enterotoxins and alpha defensin 5 expansion in the Crohn’s colitis: A new insight into the etiopathogenetic and differentiation triggers driving colonic inflammatory bowel disease

• DOI: 10.1371/journal.pone.0246393
• Publication Date: 2021-03-09T18:31:13Z
• Authors: Tanu Rana; Olga Y. Korolkova; Girish Rachakonda; Amanda D. Williams; Alexander T. Hawkins; Samuel D. James; Amos M. Sakwe; Nian Hui; Li Wang; Chang Yu; Jeffrey S. Goodwin; Michael G. Izban; Regina S. Offodile; Mary K. Washington; Billy R. Ballard; Duane T. Smoot; Xuan-Zheng Shi; Digna S. Forbes; Anil Shanker; Amosy E. M’Koma
• Keywords: Paneth cell; Goblet cell

Evidence link bacterial enterotoxins to apparent crypt-cell like cells (CCLCs), and Alpha Defensin 5 ( DEFA5 ) expansion in the colonic mucosa of Crohn’s colitis disease (CC) patients. These areas ectopic ileal metaplasia, positive for Paneth cell (PC) markers are consistent with diagnosis CC. Retrospectively, we: 1. Identified 21 patients indeterminate (IC) between 2000–2007 were reevaluation their final clinical 2014 after a followed-up mean 8.7±3.7 (range, 4–14) years. Their initial biopsies analyzed by bioassay. 2. Differentiated ulcer-associated lineage (UACL) analysis immunohistochemistry (IHC) CC patients, stained Mucin 6 (MUC6) . 3 Treated human immortalized epithelial (NCM460) colonoids pure on secretion signatures 24hr. The control not treated. 4 with/without 14 days spent medium collected determined quantitative expression , CCLCs other biologic signatures. experiments repeated twice. Three statistical methods used: (i) Univariate analysis; (ii) LASSO; (iii) Elastic net. bioassay discriminated ulcerative (UC) cohort IC accuracy. A fit logistic model group UC as outcome independent variable differentiator predictive value 96 percent. IHC staining MUC6 different locations indicating that is co-expressed UACL therefore NOT genesis CC, rather secretagogue specific signature(s) underlie distinct crypt pathobiology Notably, we observed treatment NCM460 expressed at times, intervals, intensity. factors key stem niche regulators leading secreting differentiation ‘the ectopy metaplasia formation’ conspicuously pathogenic importance