Diet, Metabolites, and ‘‘Western-Lifestyle’’ Inflammatory Diseases

Alison N. Thorburn,1,2 Laurence Macia,1,2 and Charles R. Mackay1,*
1Department of Immunology, Monash University, Clayton, VIC 3800, Australia
2Co-first author
*Correspondence: [email protected]

One explanation for the increased incidence of allergies, asthma, and even some autoimmune diseases has
been the hygiene hypothesis. However, recent studies also highlight an important role for diet and bacterial
metabolites in controlling various immune pathways, including gut and immune homeostasis, regulatory
T cell biology, and inflammation. Dietary-related metabolites engage ‘‘metabolite-sensing’’ G-proteincoupled
receptors, such as GPR43, GPR41, GPR109A, GPR120, and GPR35. These receptors are expressed
on immune cells and some gut epithelial cells and generally mediate a direct anti-inflammatory effect. Insufficient
intake of ‘‘healthy foodstuffs’’ adversely affects the production of bacterial metabolites. These metabolites
and those derived directly from food drive beneficial downstream effects on immune pathways. We
propose that insufficient exposure to dietary and bacterial metabolites might underlie the development of
inflammatory disorders in Western countries. This review highlights what is currently known about diet,
metabolites, and their associated immune pathways in relation to the development of inflammatory disease.