Microbial Regulation of Host Physiology by Short-chain Fatty Acids

Our ancestral diet consisted of much more nondigestible fiber than that of many societies today. Thus, from an evolutionary perspective the human genome and its physiological and nutritional requirements are not well aligned to modern dietary habits. Fiber reaching the colon is anaerobically fermented by the gut bacteria, which produce short-chain fatty acids (SCFAs) as metabolic by-products. SCFAs play a role in intestinal homeostasis, helping to explain why changes in the microbiota can contribute to the pathophysiology of human diseases. Recent research has shown that SCFAs can also have effects on tissues and organs beyond the gut, through their circulation in the blood. SCFAs not only signal through binding to cognate G-protein-coupled receptors on endocrine and immune cells in the body but also induce epigenetic changes in the genome through effects on the activity of histone acetylase and histone deacetylase enzymes. Furthermore, epigenetic imprinting likely occurs in utero, highlighting the importance of the maternal diet in early life. Here we review current understanding of how SCFAs impact on human and animal physiology and discuss the potential applications of SCFAs in the prevention and treatment of human diseases. Short chain fatty acids (SCFAs) contribute to intestinal homeostasis and the regulation of energy metabolism.SCFAs circulating in the blood influence tissue-specific acetylation of histones 3 and 4 in a tissue-specific fashion.Delivery of SCFAs to the colon, using specialized diets, prevents onset of diabetes in nonobese diabetic (NOD) mice.During gestation, SCFAs can cause epigenetic imprinting in utero and protect against allergic airway disease.SCFAs regulate the blood–brain barrier and neuroimmunoendocrine functions.