The effect of TNF on the colonic microbiome and acute colitis
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Inflammatory bowel disease affects approximately 1.4 million people in the United States and consists of two disorders, ulcerative colitis and Crohns disease (CD). CD is a chronic condition, primarily mediated by T helper (Th)1 and Th17 effector responses. Tumor necrosis factor (TNF) is a promoter of inflammation in CD and pharmacological blockade of TNF reduces inflammation in many CD patients. Elucidation of the exact mechanism of action of antiTNF therapy, as well as the potential effect of TNF on the microbiome is needed. Using the chemical trinitrobenzene sulfonic acid (TNBS) to induce acute CDlike colitis in wild type (WT) and TNF deficient (Tnf /) mice, we found that lack of TNF resulted in diminished colitis, indicating that TNF is proinflammatory in TNBS acute colitis. Microbial community structures were compared using Denaturing Gradient Gel Electrophoresis (DGGE) of 16S rRNA genes amplified by PCR using DNA extracted from fecal samples taken before and 72 hours after TNBS colitis induction. PCRDGGE profiles of microbial communities Tnf / and WT mice were distinctly different and clustered separately using Dice similarity comparisons. After TNBS treatment, changes in microbial profiles were greater in the Tnf / mice than WT mice. Currently MiSeq2000 Illumina sequencing of the samples are being performed for a more indepth characterization of the microbiome. Our preliminary findings emphasize the potential integrated role of the microbiota and TNF in promoting colitis.
