One explanation for the increased incidence of allergies, asthma, and certain autoimmune diseases has been the hygiene hypothesis. However, recent studies highlight the profound effects of diet and bacterial metabolites on disease in mouse models, and humans. Bacterial metabolites, such as the short-chain fatty acids, affect various systems including gut and immune homeostasis, regulatory T-cell biology, and the control of inflammation. Bacterial or dietary metabolites engage “metabolite-sensing” G-protein coupled receptors such as GPR43, GPR41, GPR109A, GPR120, and GPR35. These receptors are expressed by immune cells and some gut epithelial cells and generally play antiinflammatory roles. In addition, certain metabolites also influence immune responses through the regulation of gene transcription, for instance, butyrate inhibition of histone deacetylase activity, or tryptophan metabolites, that agonizes the aryl hydrocarbon receptor transcription factor. We argue that insufficient intake healthy foodstuffs adversely affects the production of beneficial metabolites (both bacterial and nonbacterial), and this underlies the development of inflammatory disorders in Western lifestyle countries, including many autoimmune diseases. It is likely that many cases of autoimmune disease may be preventable with healthy diets. In addition, “medicinal foods” may replace or complement traditional pharmaceutical treatments for autoimmune diseases.
