title: Ablation of tumor necrosis factor is associated with decreased inflammation and alterations of the microbiota in a mouse model of inflammatory bowel disease.
abstract: Inflammatory bowel disease (IBD) is associated with prolonged, excess secretions of Tumor Necrosis Factor (TNF). Many patients with IBD have successful management of IBD symptoms by blocking TNF secretion or signaling. However, some patients are non-responsive to this therapy, eventually become refractory to therapy, or may develop harmful side-effects [corrected]. Alterations in the microbiota that are associated with the lack of TNF could be a contributing cause of this therapeutic insufficiency seen in some patients. Here we use wildtype (WT) and mice lacking Tnf (Tnf-/-) in an acute TNBS colitis model to investigate the role of TNF in colitis and how its presence or absence affects the colonic microbiota. As expected, Tnf-/- had less severe inflammation than WT mice. Microbiome analysis revealed significant Tnf dependent-differences in alpha and beta diversity. There were also notable differences in many species that were also primarily Tnf dependent. Taken together, our data indicates that TNF contributes significantly to the inflammation and microbiotal alterations in that occur in IBD.
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Yava L
authors.initials: YL
authors.lastname: Jones-Hall
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, United States of America; Purdue University Interdisciplinary Life Science Program (PULSe), West Lafayette, Indiana, United States of America.
authors.forename: Ariangela
authors.initials: A
authors.lastname: Kozik
authors.affiliation: Department of Agronomy, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Cindy
authors.initials: C
authors.lastname: Nakatsu
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification* / Q000235:genetics; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000235:genetics* / Q000382:microbiology* / Q000628:therapy; D004269:DNA, Bacterial / Q000032:analysis; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D051379:Mice; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004269:DNA, Bacterial; D014409:Tumor Necrosis Factor-alpha; D014302:Trinitrobenzenesulfonic Acid