Ablation of tumor necrosis factor is associated with decreased inflammation and alterations of the microbiota in a mouse model of inflammatory bowel disease

PloS One
Yava L Jones-HallCindy Nakatsu

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.

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Citations

Mar 5, 2016·Gut Microbes·Yava L Jones-Hall, Cindy H Nakatsu
Jan 23, 2018·Digestive Diseases and Sciences·Antony CougnouxForbes D Porter
Oct 24, 2017·Immunological Investigations·Barbara E Ostrov, Daniel Amsterdam
Jan 22, 2019·Nature Medicine·Bahtiyar YilmazAndrew J Macpherson
Apr 24, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Viviani MendesAngelica Thomaz Vieira
Jan 24, 2018·Inflammatory Bowel Diseases·Cynthia Reinoso WebbMatthew B Grisham
Jun 2, 2020·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Sonia FacchinEdoardo Vincenzo Savarino
May 11, 2016·FEMS Microbiology Ecology·Rangel IgnacioHultgren-Hörnquist Elisabeth
Jul 19, 2018·Inflammatory Intestinal Diseases·Charles N Bernstein, Jessica D Forbes
Sep 19, 2019·Molecular Nutrition & Food Research·Lifeng GuiZhiguo Liu
Nov 28, 2017·Experimental and Molecular Pathology·Ariangela J KozikYava L Jones-Hall
May 1, 2021·Cancers·Ekaterina O GubernatorovaSergei A Nedospasov
Jun 5, 2021·BMC Microbiology·Jinhee KimRonaldo P Ferraris

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Methods Mentioned

BETA
light microscopy
electrophoresis
PCR
Assay
Illumina sequencing

Software Mentioned

ORD
PERMDISP
perMANOVA
PC
Illumina
QIIME
Panda
Unifrac
Greengenes

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