The underlying reason for non-responders to anti-TNF therapy can be varied, but to date a definitive reason has not been defined. Thus, more focused therapeutic strategies are needed. Despite intense study, the underlying Diprenorphine etiology and mechanism of pathogenesis of CD remain to be fully elucidated. Altered microbiota and excessive inflammation are two major components that contribute to the development and progression of CD and studies detailing changes in the microbiome that occur as disease progresses from acute colitis to chronic colitis are limited.We hypothesize that neutralization of TNF induces alterations in the intestinal microbiota that correlate with reduced inflammation. In this study, we use the trinotrobenzene sulfonic acid colitis mouse model of CD to evaluate the colonic microbiota in healthy and colitic animals that produce Tnf or lack Tnf in order to determine how TNF suppression correlates with alterations in the microbiota and decreased inflammation. Our long term goal is to identify specific microbial communities that can be manipulated, in addition to TNF suppression, to increase the effectiveness of the anti-TNF therapeutic protocol. In this study, we evaluated how TNF ablation affects acute colitis, and how colitis correlates with TNF EGLU dependent alterations in the microbiota. As expected, we found that TNF promotes acute TNBS colitis, and CCA indicated colitis scores corresponded with alterations in the colonic microbiota. The decreased inflammation in TNF- mice is consistent with previous reports. Similarly, treatment of mice with an anti-TNF monoclonal antibody also caused decreased mucosal cellular infiltration and down regulation of pro-inflammatory cytokine levels. Anti-TNF antibody administration resulted in significant apoptosis of macrophages in the lamina propria or of enterocytes, which was considered to be the most likely mechanism of disease remission.We believe that these findings support the accepted theory that TNF is a master regulator and is critical in acute inflammatory responses and that the lack of TNF production or signaling resulted in decreased colitis, which otherwise would likely have proceeded uninhibitedly. Additionally, TNF has been shown to inhibit the repair of the gut epithelium via increasing the number of apoptotic cells in both mice and humans, which contributes to the inflammation associated with the translocation of bacteria. Here, we expanded upon these studies and included investigations of the effect of TNF-depletion on the intestinal microbiota. Beta diversity comparisons revealed that the most significant difference in communities was due to mouse genotype. At the phylum level this difference was likely due to the higher Firmicutes to Bacteroidetes ratio in WT vs Tnf-/- mice. This differs from a study that used anti-TNF- �� to inhibit TNF production in mice in which the Firmicutes to Bacteroidetes ratio decrease but no information was given if this difference was significant.