Moreover, even different strains or mutants of particular Lactobacillus species stimulated very different immunological outcomes in mice [16,17]. Recent evidence demonstrates that colonization of germ-free mice with complex microbiota orchestrated a broad spectrum of Th1, Th17 and Treg responses. Whereas most tested individual bacteria failed to stimulate intestinal T cell responses efficiently, a

restricted number of individual bacteria can control the tonicity of the gut immune system [18]. The key commensal organisms in immune system development have been identified very recently as segmented filamentous bacteria [18,19]. A further reflection of how the make-up of the intestinal flora can impact upon systemic responses is found in studies of non-obese diabetic (NOD) mice, which succumb spontaneously see more to type 1 diabetes (T1D); it has been known for some time that higher microbial exposure militates against development of this autoimmune disease [20], but it was shown recently not only that conventionally housed myeloid differentiation primary response gene 88 (MyD88)−/− mice are resistant to T1D, but that resistance to disease is due to the distinct microbial

combination with which they are colonized. Hence, MyD88−/− mice develop T1D under germ-free conditions, while wild-type mice given the microbial population from MyD88−/− animals had reduced susceptibility to disease [21]. It is tempting

to speculate that alteration of Treg homeostasis mediated by TLR signalling, either because of Histone Methyltransferase inhibitor genetic polymorphism or because of changes in gut flora composition, could also have consequences on development of gut inflammatory disorders. Indeed, gut flora bacteria are not equal in their capacity to stimulate TLR-9 and do so with various levels of efficiency that correlate with the frequency of cytosine–guanine dinucleotides. Thus, control of the Treg ratio and effector T cell function in the GI tract is likely to be regulated differentially by specific gut flora species. An illustration of how the presence of defined bacterial species can influence the outcome of an infection comes from the observation that mice fed Bifidobacterium Celecoxib infantis are protected from the pathogenic effect and translocation of Salmonella[22]. Activation of Tregs by the probiotic microorganism contributed to this protective effect. The proposition that certain commensal species may act in a counterinflammatory manner has led to extensive investigation of potential probiotic regulation of immunopathology. Promising results have been obtained with probiotics in the treatment of human inflammatory diseases of the intestine and in the prevention and treatment of atopic eczema in neonates and infants, but mechanism(s) of action remain to be elucidated [23].