title: Fusobacterium nucleatum infection of colonic cells stimulates MUC2 mucin and tumor necrosis factor alpha.
abstract: The etiology of inflammatory bowel disease is not completely known, but it is influenced by the presence of normal gut microflora as well as yet-unrecognized pathogens. The anaerobic, Gram-negative bacterial species Fusobacterium nucleatum is a common resident of the human mouth and gut and varies in its pathogenic potential. In this study, we demonstrate that highly invasive F. nucleatum isolates derived from the inflamed guts of Crohn's disease patients evoked significantly greater MUC2 and tumor necrosis factor alpha (TNF-α) gene expression than minimally invasive strains isolated from the noninflamed gut in human colonic epithelial cells and in a rat ligated colonic loop model of infection. Only live F. nucleatum induced mucin secretion and TNF-α expression in direct contact with and/or during invasion of colonic cells. In rat colons, mucin secretion was augmented in response to a highly invasive F. nucleatum isolate but was unaffected by treatment with a minimally invasive strain. Taken together, these studies reveal that F. nucleatum may represent a challenging pathogen in the etiology of gut inflammatory diseases and highlight the importance of different pathotypes of candidate bacterial species in disease pathogenesis.
authors.affiliation: Gastrointestinal Research Group, Health Sciences Centre, University of Calgary, 3330 Hospital Drive, NW, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Poonam
authors.initials: P
authors.lastname: Dharmani
authors.forename: Jaclyn
authors.initials: J
authors.lastname: Strauss
authors.forename: Christian
authors.initials: C
authors.lastname: Ambrose
authors.forename: Emma
authors.initials: E
authors.lastname: Allen-Vercoe
authors.forename: Kris
authors.initials: K
authors.lastname: Chadee
mesh_terms: D000328:Adult; D000818:Animals; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D003424:Crohn Disease / Q000382:microbiology; D005260:Female; D005455:Fluorescent Antibody Technique; D005674:Fusobacterium Infections / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D016967:Fusobacterium nucleatum / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity*; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D055262:Mucin-2 / Q000096:biosynthesis* / Q000235:genetics; D009077:Mucins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C524625:MUC2 protein, human; D055262:Mucin-2; D009077:Mucins; D014409:Tumor Necrosis Factor-alpha