The main end products of fermentation by the microbiota are shortchain fatty acids, typically acetate, propionate and butyrate which are largely absorbed and metabolized by the host organism. SCFA can act as signaling molecules and regulate energy metabolism and inflammatory responses in the host. They also play important roles as substrates for glucose, cholesterol and lipid metabolism providing up to 10% of the daily caloric intake. Microbial metabolism can also affect gut-hormone production and intestinal permeability causing elevated systemic levels of lipopolysaccharide which contributes to the low-grade systemic inflammation associated with obesity and metabolic syndrome. Obesity is associated with changes in the abundance at the level of phylum, genus or species of gut microbiota. In mice, Firmicutes is increased and Bacteroidetes decreased in obese animals but, in humans, differences between obese and normal-weight individuals as well as changes following weight reduction due to caloricrestriction are not consistent.The basal transcriptional machinery and more importantly with TBP to drive initiation of transcription. Specifically, the interaction between VP16 has been shown to stabilize TBP to the TATA-box and synergistically activate gene expression. Hence, it is likely that VP64-TALEs stabilize TBP-TALE to cytokine gene promoters through cooperative interactions and this led to synergistic activation of cytokine genes. Additional data to support this notion is supported by a few instances in TBP-TALE experiments. As shown in Figures 2A and 2B, two TALE combinations using TBP-TALE demonstated an apparent reduction in IL-2 gene expression and appreciable levels of enhanced synergy at the transcriptional level was only demonstrated when using multiple VP64-TALE activators coupled with TBP-TALE. We speculate that in these instances, TBPTALE binding and subsequent bending of the DNA, a natural function of TBP, directly influenced its cooperative interaction with the neighboring VP64-TALE leading to a reduction in gene activation. However, as the number of VP64-TALEs increased, this stabilized TBP-TALE to the gene promoter leading to enhanced IL-2 gene activation. Taken together, we speculate that cooperative and reciprocal interactions between TBP-TALE and VP64-TALEs enables them to effectively initiate robust transcriptional activation of silenced genes. For example, the data in Figure 2A and 2B demonstrate that TBP-TALEs differentially influence the extent of synergistic effect, with IL2B-TBP enhancing synergy two times more efficiently than IL2D-TBP. The distance between IL2B-TBP and an adjacently located VP64-TALE is 5 bp in contrast to 20 bp for IL2D-TBP, with the former enhancing gene activation up to 4-fold and the latter only,2fold. A recent study reports a similar position effect on gene activation between adjacent DNA-bound transcription factors.