Acute colitis induced by the barrier-damaging agent dextransulfate- sodium is exacerbated by gut bacteria, as evidenced by the amelioration of inflammation in germ-free animals and in mice treated with antibiotics. Early studies on roles of bacterial LPS in triggering acute intestinal inflammation revealed that LPS-hyporesponsive C57BL and C3H mice displayed reduced macroscopic signs of colitis as compared to controls and were protected from inflammatory responses initiated by elevated serum LPS levels during inflammation. Another study reported that DSS-induced colitis activity varies with the mouse strain used, but claims that the severity of colitis does not differ in LPS-unresponsive as compared to control mice, irrespective of their genetic background. Furthermore, TLR-mediated sensing of gut bacteria has been suggested to play a role in intestinal homeostasis and TLR4 was shown to limit bacterial translocation during colitis. In contrast, recent findings demonstrated that TLR-signaling via the adapter protein MyD88 is essential for spontaneous development of colitis in IL10-deficient mice. However, global gut flora analysis in DSS-induced barrier-damage, which could account for some of the contradictory results mentioned above, has not been performed and bacterial species most abundant in acute colitis have not been investigated so far. To further extend our knowledge on potential roles of a bacterial interplay with innate immunity in acute colitis, we performed a global survey of the intestinal microflora and determined numbers of inflammatory cells in DSS-treated C57BL/10 mice lacking TLRs 2 and/or 4. Because major groups of gut bacteria cannot be cultivated, we complemented classical microbiological analyses with culture-independent molecular approaches such as denaturing-gradient-gel-electrophoresis based on separation of PCR-amplified bacterial 16S rRNA gene fragments. Vismodegib inquirer Besides identification of gut residents specifically associated with the severity of DSS-induced colitis, we also studied the impact of TLRs 2 and 4 on i) macroscopic signs of acute colitis, ii) changes in relevant immune cell populations in the inflamed colon, and iii) the composition and dynamics of the intestinal microflora in healthy and diseased TLR-deficient animals. This is consistent with similar observations in IBD, where inflamed tissue areas contained higher numbers of FOXP3- positive T-cells. Taken together and in line with recent findings, our results PLX-4720 Raf inhibitor underline the important role of gut bacterial sensing by TLRs in maintaining the intricate balance between mucosal immunity and intestinal inflammation. The results obtained here add important information in as much as bacterial TLR2 ligands may contribute to colitis pathology. Autism and psychotic disorders have historically been considered as related diagnostic entities.