Fig. 1.

Factors at the commensal-host interface associated with health and disease. Environmental and host factors (which are under genetic control) determine the composition and functional consequences of the components within the lumenal milieu. The lumenal milieu consists of commensal microbiota and their products and secreted factors of the host (blue). These lumenal states are metastable at any given point in time and likely age-dependent. Health is associated with symbiosis of the commensal microbiota and host responses (lumenal, epithelial, and subepithelial), which are a reflection of homeostasis. Disease on the other hand is characterized by dysbiosis of the commensal microbiota and the corollary host responses. Whether symbiosis or dysbiosis is a primary or secondary factor in disease development remains an open question. The ultimate development of disease at any given set point in this model is dependent on many factors, which determine tissue tolerance and include genetic susceptibility among others. GPCR43, G protein–coupled receptor 43; PSA, polysaccharide antigen A; Treg, T regulatory cell; ER, endoplasmic reticulum; wt, wild-type allele; mut, mutant allele; TMA, trimethylamine; Th, T helper; IL, interleukin; TGFβ, transforming growth factor–β; IFNγ, interferon-γ; iNKT, invariant natural killer T.