Research Progress in Regulation of Allergic Diseases by Short-Chain Fatty Acids

SHI Yan-biao, GAO Si-jia, WANG Hui

Abstract

Gut microbiota-derived metabolites play vital roles in the regulation of host-gut microbiota mutualism, gut homeostasis and the pathogenesis of multiple human diseases. Fermentation of indigestible dietary fibers by gut microbiota produces a variety of short-chain fatty acids (SCFAs) consisting mainly of acetate, propionate and butyrate. Despite high concentrations of SCFAs in the gut, it has been reported in a large number of studies that SCFAs are involved in the onset and development of multiple diseases, including colitis, diabetes mellitus, hepatic steatosis, and obesity. Recent studies including our work found that SCFAs regulates allergic immune reactions and the pathogenesis of allergic diseases via their action on allergic effector immune cells, including T helper 2 (Th2) cells, type 2 innate lymphoid cells (ILC2), eosinophils, mast cells and basophils. Herein, we reviewed the association of SCFAs with human allergic diseases, their role in regulating the animal model of allergic diseases and the effects of different SCFAs in regulating the functions of allergic effectors cells and the underlying mechanisms, aiming to provide research clues for in-depth investigation in the role played by SCFAs in regulating various allergic diseases.

 

Keywords: Short-chain fatty acid, Propionate, Butyrate, Allergic diseases, Histone deacetylase inhibitors

 

Full Text:

PDF


References


HONDA K， LITTMAN D R. The microbiota in adaptive immune homeostasis and disease. Nature，2016，535(7610): 75–84.

MASLOWSKI K M， VIEIRA A T， NG A， et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature，2009，461(7268): 1282–1286.

ERNY D， HRABE DE ANGELIS A L， JAITIN D， et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci，2015，18(7): 965–977.

SINGH N， GURAV A， SIVAPRAKASAM S， et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity，2014， 40(1): 128–139.

KOETH R A， WANG Z， LEVISON B S， et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med，2013，19(5): 576–585.

ROOKS M G， GARRETT W S. Gut microbiota, metabolites and host immunity. Nat Rev Immunol，2016，16(6): 341–352.

TAN J， MCKENZIE C， POTAMITIS M， et al. The role of short-chain fatty acids in health and disease. Adv Immunol，2014，121: 91–119.

DALILE B， VAN OUDENHOVE L， VERVLIET B， et al. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat Rev Gastroenterol Hepatol，2019，16(8): 461–478.

AGACHE I， AKDIS C A. Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes of allergic diseases. J Clin Invest， 2019，129(4): 1493–1503.

CUMMINGS J H， POMARE E W， BRANCH W J， et al. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut，1987，28(10): 1221–1227.

SCHONFELD P， WOJTCZAK L. Short- and medium-chain fatty acids in energy metabolism: the cellular perspective. J Lipid Res，2016，57(6): 943–954.

BLOEMEN J G， VENEMA K， VAN DE POLL M C， et al. Short chain fatty acids exchange across the gut and liver in humans measured at surgery. Clin Nutr，2009，28(6): 657–661.

SELTZER M A， JAHAN S A， SPARKS R， et al. Radiation dose estimates in humans for (11)C-acetate whole-body PET. J Nucl Med，2004，45(7): 1233–1236.

NIEDERMAN R， BUYLE-BODIN Y， LU B Y， et al. Short-chain carboxylic acid concentration in human gingival crevicular fluid. J Dent Res，1997，76(1): 575–579.

GHORBANI P， SANTHAKUMAR P， HU Q， et al. Short-chain fatty acids affect cystic fibrosis airway inflammation and bacterial growth. Eur Respir J，2015，46(4): 1033–1045.

PAPARO L， NOCERINO R， CIAGLIA E， et al. Butyrate as a bioactive human milk protective component against food allergy. Allergy，2021， 76(5): 1398–1415.

LE POUL E， LOISON C， STRUYF S， et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J Biol Chem，2003，278(28): 25481–25489.

THANGARAJU M， CRESCI G A， LIU K， et al. GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res，2009，69(7): 2826–2832.

PRIYADARSHINI M， KOTLO K U， DUDEJA P K， et al. Role of short chain fatty acid receptors in intestinal physiology and pathophysiology. Compr Physiol，2018，8(3): 1091–1115.

TAZOE H， OTOMO Y， KARAKI S， et al. Expression of short-chain fatty acid receptor GPR41 in the human colon. Biomed Res，2009，30(3): 149–156.

NOHR M K， EGEROD K L， CHRISTIANSEN S H， et al. Expression of the short chain fatty acid receptor GPR41/FFAR3 in autonomic and somatic sensory ganglia. Neuroscience，2015，290: 126–137.

THEILER A， BARNTHALER T， PLATZER W， et al. Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival. J Allergy Clin Immunol，2019，144(3): 764–776.

WEN T， ARONOW B J， ROCHMAN Y， et al. Single-cell RNA sequencing identifies inflammatory tissue T cells in eosinophilic esophagitis. J Clin Invest，2019，129(5): 2014–2028.

SHI Y， XU M， PAN S， et al. Induction of the apoptosis, degranulation and IL-13 production of human basophils by butyrate and propionate via suppression of histone deacetylation. Immunology，2021，164(2): 292–304.

THIO C L， CHI P Y， LAI A C， et al. Regulation of type 2 innate lymphoid cell-dependent airway hyperreactivity by butyrate. J Allergy Clin Immunol，2018，142(6): 1867–1883 e12.

KARAKI S， MITSUI R， HAYASHI H， et al. Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. Cell Tissue Res，2006，324(3): 353–360.

BROWN A J， GOLDSWORTHY S M， BARNES A A， et al. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem，2003， 278(13): 11312–11319.

TUNARU S， KERO J， SCHAUB A， et al. PUMA-G and HM74 are receptors for nicotinic acid and mediate its anti-lipolytic effect. Nat Med， 2003，9(3): 352–355.

TAGGART A K， KERO J， GAN X， et al. (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J Biol Chem，2005，280(29): 26649–26652.


Refbacks

  • There are currently no refbacks.