Epigenome targeting by probiotic metabolites

Probiotic bacteria have diverse effects including altering microbiota composition, regulating epithelial cell barrier function and modulating of immune responses. The precise molecular mechanisms mediating these probiotic effects are not well understood. Short-chain fatty acids such as butyrate are a class of histone deacetylase inhibitors important in the epigenetic control of host cell responses. It is hypothesized that the biological function of probiotics may be a result of epigenetic modifications that may explain the wide range of effects observed. Studies delineating the effects of probiotics on short-chain fatty acid production and the epigenetic actions of short-chain fatty acids will assist in understanding the association between microbiota and allergic or autoimmune disorders.We propose that treatment with specific probiotic bacteria under in vivo conditions would offer the ideal conditions to examine the microbiological, immunological and epigenetic mechanisms of action. Advances in epigenetic technology now allow investigators to better understand the complex biological properties of probiotics and their metabolites.Determining the precise mechanisms of probiotic action will lead to more specific and efficacious therapeutic strategies in the prevention or treatment of chronic inflammatory conditions.The intestinal microbiota plays a critical role in the establishment and maintenance of healthy immune responses. Delayed colonisation of the infant gut with commensal bacteria or alterations in the microbiota profile are suggested to be strong risk factors for the development of immune-mediated chronic disorders such as allergic and autoimmune diseases. Mice raised in a germ- free environment fail to develop oral tolerance and have persistent Th2-dependent immune responses [1]. This immune deviation can be corrected by reconstituting the microbiota with a single bacteria species, but only if this occurs during the neonatal period. Similarly, infants with a