Short-Chain Fatty Acid and FFAR2 Activation – A New Option for Treating Infections?

The human innate immune system is equipped with multiple mechanisms to detect microbe-associated molecular patterns (MAMPs) to fight bacterial infections. The metabolite short-chain fatty acids (SCFAs) acetate, propionate and butyrate are released by multiple bacteria or are food ingredients. SCFA p...

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Autores principales:	Katja Schlatterer, Andreas Peschel, Dorothee Kretschmer
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	short-chain fatty acids GPR43/FFAR2 infectious diseases antimicrobial resistance therapeutic application multidrug resistant infections Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/331008176197465e9cf25932722d8374
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spelling	oai:doaj.org-article:331008176197465e9cf25932722d83742021-12-02T10:16:22ZShort-Chain Fatty Acid and FFAR2 Activation – A New Option for Treating Infections?2235-298810.3389/fcimb.2021.785833https://doaj.org/article/331008176197465e9cf25932722d83742021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.785833/fullhttps://doaj.org/toc/2235-2988The human innate immune system is equipped with multiple mechanisms to detect microbe-associated molecular patterns (MAMPs) to fight bacterial infections. The metabolite short-chain fatty acids (SCFAs) acetate, propionate and butyrate are released by multiple bacteria or are food ingredients. SCFA production, especially acetate production, is usually essential for bacteria, and knockout of pathways involved in acetate production strongly impairs bacterial fitness. Because host organisms use SCFAs as MAMPs and alter immune reactions in response to SCFAs, interventions that modulate SCFA levels can be a new strategy for infection control. The interaction between SCFAs and host cells has been primarily investigated in the intestinal lumen because of the high local levels of SCFAs released by bacterial microbiome members. However, members of not only the intestinal microbiome but also the skin microbiome produce SCFAs, which are known ligands of the seven-transmembrane G-protein-coupled receptor FFAR2. In addition to enterocytes, FFAR2 is expressed on other human cell types, including leukocytes, especially neutrophils. This finding is in line with other research that determined that targeted activation of FFAR2 diminishes susceptibility toward various types of infection by bacteria such as Klebsiella pneumonia, Citrobacter rodentium, and Staphylococcus aureus but also by viruses such as respiratory syncytial and influenza viruses. Thus, our immune system appears to be able to use FFAR2-dependent detection of SCFAs for perceiving and even averting severe infections. We summarize recent advances in understanding the role of SCFAs and FFAR2 in various infection types and propose the manipulation of this receptor as an additional therapeutic strategy to fight infections.Katja SchlattererKatja SchlattererKatja SchlattererAndreas PeschelAndreas PeschelAndreas PeschelDorothee KretschmerDorothee KretschmerDorothee KretschmerFrontiers Media S.A.articleshort-chain fatty acidsGPR43/FFAR2infectious diseasesantimicrobial resistancetherapeutic applicationmultidrug resistant infectionsMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	short-chain fatty acids GPR43/FFAR2 infectious diseases antimicrobial resistance therapeutic application multidrug resistant infections Microbiology QR1-502
spellingShingle	short-chain fatty acids GPR43/FFAR2 infectious diseases antimicrobial resistance therapeutic application multidrug resistant infections Microbiology QR1-502 Katja Schlatterer Katja Schlatterer Katja Schlatterer Andreas Peschel Andreas Peschel Andreas Peschel Dorothee Kretschmer Dorothee Kretschmer Dorothee Kretschmer Short-Chain Fatty Acid and FFAR2 Activation – A New Option for Treating Infections?
description	The human innate immune system is equipped with multiple mechanisms to detect microbe-associated molecular patterns (MAMPs) to fight bacterial infections. The metabolite short-chain fatty acids (SCFAs) acetate, propionate and butyrate are released by multiple bacteria or are food ingredients. SCFA production, especially acetate production, is usually essential for bacteria, and knockout of pathways involved in acetate production strongly impairs bacterial fitness. Because host organisms use SCFAs as MAMPs and alter immune reactions in response to SCFAs, interventions that modulate SCFA levels can be a new strategy for infection control. The interaction between SCFAs and host cells has been primarily investigated in the intestinal lumen because of the high local levels of SCFAs released by bacterial microbiome members. However, members of not only the intestinal microbiome but also the skin microbiome produce SCFAs, which are known ligands of the seven-transmembrane G-protein-coupled receptor FFAR2. In addition to enterocytes, FFAR2 is expressed on other human cell types, including leukocytes, especially neutrophils. This finding is in line with other research that determined that targeted activation of FFAR2 diminishes susceptibility toward various types of infection by bacteria such as Klebsiella pneumonia, Citrobacter rodentium, and Staphylococcus aureus but also by viruses such as respiratory syncytial and influenza viruses. Thus, our immune system appears to be able to use FFAR2-dependent detection of SCFAs for perceiving and even averting severe infections. We summarize recent advances in understanding the role of SCFAs and FFAR2 in various infection types and propose the manipulation of this receptor as an additional therapeutic strategy to fight infections.
format	article
author	Katja Schlatterer Katja Schlatterer Katja Schlatterer Andreas Peschel Andreas Peschel Andreas Peschel Dorothee Kretschmer Dorothee Kretschmer Dorothee Kretschmer
author_facet	Katja Schlatterer Katja Schlatterer Katja Schlatterer Andreas Peschel Andreas Peschel Andreas Peschel Dorothee Kretschmer Dorothee Kretschmer Dorothee Kretschmer
author_sort	Katja Schlatterer
title	Short-Chain Fatty Acid and FFAR2 Activation – A New Option for Treating Infections?
title_short	Short-Chain Fatty Acid and FFAR2 Activation – A New Option for Treating Infections?
title_full	Short-Chain Fatty Acid and FFAR2 Activation – A New Option for Treating Infections?
title_fullStr	Short-Chain Fatty Acid and FFAR2 Activation – A New Option for Treating Infections?
title_full_unstemmed	Short-Chain Fatty Acid and FFAR2 Activation – A New Option for Treating Infections?
title_sort	short-chain fatty acid and ffar2 activation – a new option for treating infections?
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/331008176197465e9cf25932722d8374
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Short-Chain Fatty Acid and FFAR2 Activation – A New Option for Treating Infections?

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