This lecture first highlights the methods available to detect bacterial translocation (BT) as well as shortcomings related to those. Secondly, mechanisms involved in the process of BT with special focus on intestinal flora, gut barrier dysfunction and the role of immune defence mechanisms are discussed. Thirdly, the potentially huge clinical relevance of BT is reviewed. BT is the key to our understanding of spontaneous bacterial peritonitis in liver cirrhosis, the multiorgan failure syndrom induced by hemorrhagic shock, burns or sepsis and is involved in a multitude of diverse gastrointestinal lesions. Therefore, BT may represent a common and so far inadequately recognized trigger for a multitude of complications known for long in various clinical entities. Finally, the focus will be to discuss advances in therapeutic approaches in preventing BT and associated potential complications. There is much evidence linking diet with the maintenance of intestinal integrity and multiple enteral manoveures have been tested. Particularly promising is the avenue of using probiotics known to exert many effects and to protect the gut from BT. Various other therapeutic approaches include binding/neutralizing of endotoxins, hyperbaric oxygen, prostaglandins, antioxidans etc. A more general attempt to reduce the presumed risk of BT is selective gut decontamination (SGD). In summary, the concept of BT contributing to morbidity is of extraordinary importance and its detailed investigation will eventually open an avenue for preventive measures against infectious complications.

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Butyric acid present in the culture filtrates of Porphyromonas gingivalis, Prevotella loescheii and Fusobacterium nucleatum induced cytotoxicity and apoptosis in murine thymocytes, splenic T cells, and human Jurkat T cells. A pronounced accumulation of ROS occurred during butyric acid-induced apoptosis. Butyric acid induced apoptosis via the mitochondrial apoptotic pathway, e.g. cytochrome c, AIF, and Smac, and by the ceramide pathway. Up-regulation of JNK and p38, and down-regulation of ERK occurred immediately after butyric acid treatment. In microarray analysis, butyric acid treatment resulted in increased expression of the proapoptotic gene, whereas the expression of anti-apoptotic mediators was decreased. These data suggest that butyric acid is an apoptosis-inducing agent in most lymphoreticular cells. In contrast, epithelial cells and fibroblasts were insensitive to butyric acid. Fibroblasts from healthy gingival tissue rescued butyric acid-induced T cell apoptosis via proinflammatory cytokines such as IL-6 and IL-11, which were produced by the fibroblasts stimulated by butyric acid. Furthermore, the T cell apoptosis was also down-regulated by T cell adhesion to gingival fibroblasts through interaction with CD44, VLA-2, and VLA-5 expressed on T cells stimulated with butyric acid. Also, gingival fibroblasts from periodontal patients were highly susceptible to apoptosis induced by butyric acid when compared to healthy gingival fibroblasts. In conclusion, since short-chain fatty acids produced by periodontopathic bacteria induce apoptosis in immunological cells and the fibroblasts from periodontal patients, the results strongly suggested that they are concerned with the progress of periodontal disease.

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