Abstract
BackgroundThe intestinal microbiota plays an important role in immune development and homeostasis. A disturbed microbiota during early infancy is associated with an increased risk of developing inflammatory and allergic diseases later in life. The mechanisms underlying these effects are poorly understood but are likely to involve alterations in microbial production of fermentation-derived metabolites, which have potent immune modulating properties and are required for maintenance of healthy mucosal immune responses. Probiotics are beneficial bacteria that have the capacity to alter the composition of bacterial species in the intestine that can in turn influence the production of fermentation-derived metabolites. Principal among these metabolites are the short-chain fatty acids butyrate and acetate that have potent anti-inflammatory activities important in regulating immune function at the intestinal mucosal surface. Therefore strategies aimed at restoring the microbiota profile may be effective in the prevention or treatment of allergic and inflammatory diseases.Presentation of the hypothesisProbiotic 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.Testing the hypothesisWe 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.Implications of the hypothesisDetermining the precise mechanisms of probiotic action will lead to more specific and efficacious therapeutic strategies in the prevention or treatment of chronic inflammatory conditions.
Highlights
The intestinal microbiota plays an important role in immune development and homeostasis
Testing the hypothesis: 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
The intestinal microbiota plays a critical role in the establishment and maintenance of healthy immune responses
Summary
The intestinal microbiota plays a critical role in the establishment and maintenance of healthy immune responses. Studies involving SCFA treatment using butyrate and acetate have yielded promising results, with amelioration of inflammatory lesions in mouse models of allergic airways disease and colitis [27] This has led to the idea that probiotic supplementation could restore SCFA levels by modulating the microbial environment, representing a novel therapeutic or preventative strategy for chronic inflammatory diseases. It is possible that probiotic-derived SCFA metabolites such as butyrate produce HDACi effects that have multiple downstream effector functions on many target cells, including those of the immune system This offers a promising intervention approach for the treatment of inflammatory conditions such as allergy and gastrointestinal disease.
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