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. 2021 Jan 7;13(1):167. doi: 10.3390/nu13010167

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© 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Immune regulation by carbohydrate metabolites. Lactate and pyruvate induce dendrite protrusion of intestinal CX3CR1⁺ macrophages via GRP31 to enhance the immune response. Lactate also maintains gut homeostasis via Wnt/β-catenin signaling activation to induce intestinal stem cell proliferation. SCFAs act as HDAC inhibitors or stimulators for GPCRs to regulate intestinal immune homeostasis. SCFAs induce Treg cell differentiation, plasma B cell differentiation, and IL-22 production from ILC3 as well as Th1 and Th17 cells. Additionally, SCFAs regulate the activity of certain macrophages and dendritic cells (DCs). AhR, aryl hydrocarbon receptor; ALDH, aldehyde dehydrogenase; AMPs, anti-microbial peptides; GPCRs, G protein coupled receptor; HDAC, histone deacetylase; HIF1α, hypoxia-inducible factor 1-alpha; ISC, intestinal stem cell; PPAR-γ, peroxisome proliferator-activated receptor-γ; RA, retinoic acid.