Fig. 1

Effect of SCFAs on bone marrow hematopoiesis. Fermentation of undigested dietary fibers by the gut microbiota results in the production of short-chain fatty acids (SCFAs), with propionate, acetate, and butyrate as the most abundant metabolites. SCFAs disseminate from the gut into the blood stream where they can reach the bone marrow (BM) to promote hematopoiesis. In the bone marrow, hematopoietic stem cells (HSCs) can differentiate into multipotent progenitors (MPPs) which in turn can commit to common lymphoid precursors (CLPs) or to common myeloid precursors (CMPs). CMPs can further differentiate into granulocyte and macrophage progenitors (GMPs) that commit to monocyte and DC progenitors (MDPs). MDPs can give rise to Ly6C− and Ly6C+ monocytes or to common DC precursors (CDPs). Monocytes can leave the BM and circulate as patrolling Ly6C− or inflammatory Ly6C+ monocytes in the periphery. Under inflammatory conditions, Ly6C+ monocytes can give rise to CD11b high monocyte-derived DCs (moDCs) in the lungs. CDPs differentiate into pre-classical DCs (pre-DCs) which then migrate from the bone marrow into the lungs where they can mature into CD103+ DCs or CD11b+ conventional DCs (cDCs). Ly6C− monocytes can differentiate into alternatively activated macrophages (AAMs). During house dust mite (HDM)-induced allergic airway inflammation, propionate and acetate were shown to enhance generation of MDPs and CDPs. These inflammatory DC precursor cells migrate to the lung where they can mature into CD11b high DCs that have a high phagocytic capacity but are less activated as seen by reduced expression of CD40, PD-L2, and CD86. Thus, these lung DCs have a reduced ability to induce T helper 2 (Th2) effector function and proliferation, and can therefore not sustain a Th2 cell-mediated allergic airway inflammation. During influenza infection, butyrate or propionate increase the proliferation of MDPs resulting in increased Ly6C− monocytes in the bone marrow and in the lungs. These patrolling Ly6C− monocytes can differentiate into AAMs that express lower levels of CXCL1, a neutrophil chemoattractant. Thus, neutrophil influx is reduced resulting in decreased influenza-mediated lung immunopathology. Moreover, SCFAs directly promote the activation of influenza-specific CD8+ T cells by enhancing their metabolism, and consequently their antiviral activity