Differential Modulation by <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and <named-content content-type="genus-species">Faecalibacterium prausnitzii</named-content> of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids

ABSTRACT The gut microbiota is essential for numerous aspects of human health. However, the underlying mechanisms of many host-microbiota interactions remain unclear. The aim of this study was to characterize effects of the microbiota on host epithelium using a novel ex vivo model based on mouse ile...

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Autores principales:	Sabina Lukovac, Clara Belzer, Linette Pellis, Bart J. Keijser, Willem M. de Vos, Roy C. Montijn, Guus Roeselers
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f0fac67d694c44dda4c1534155d2c36c
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spelling	oai:doaj.org-article:f0fac67d694c44dda4c1534155d2c36c2021-11-15T15:47:22ZDifferential Modulation by <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and <named-content content-type="genus-species">Faecalibacterium prausnitzii</named-content> of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids10.1128/mBio.01438-142150-7511https://doaj.org/article/f0fac67d694c44dda4c1534155d2c36c2014-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01438-14https://doaj.org/toc/2150-7511ABSTRACT The gut microbiota is essential for numerous aspects of human health. However, the underlying mechanisms of many host-microbiota interactions remain unclear. The aim of this study was to characterize effects of the microbiota on host epithelium using a novel ex vivo model based on mouse ileal organoids. We have explored the transcriptional response of organoids upon exposure to short-chain fatty acids (SCFAs) and products generated by two abundant microbiota constituents, Akkermansia muciniphila and Faecalibacterium prausnitzii. We observed that A. muciniphila metabolites affect various transcription factors and genes involved in cellular lipid metabolism and growth, supporting previous in vivo findings. Contrastingly, F. prausnitzii products exerted only weak effects on host transcription. Additionally, A. muciniphila and its metabolite propionate modulated expression of Fiaf, Gpr43, histone deacetylases (HDACs), and peroxisome proliferator-activated receptor gamma (Pparγ), important regulators of transcription factor regulation, cell cycle control, lipolysis, and satiety. This work illustrates that specific bacteria and their metabolites differentially modulate epithelial transcription in mouse organoids. We demonstrate that intestinal organoids provide a novel and powerful ex vivo model for host-microbiome interaction studies. IMPORTANCE We investigated the influence of the gut microbiota and microbially produced short-chain fatty acids (SCFAs) on gut functioning. Many commensal bacteria in the gut produce SCFAs, particularly butyrate, acetate, and propionate, which have been demonstrated to reduce the risk of gastrointestinal disorders. Organoids—small crypt-villus structures grown from ileal intestinal stem cells—were exposed to SCFAs and two specific gut bacteria. Akkermansia muciniphila, found in the intestinal mucus, was recently shown to have a favorable effect on the disrupted metabolism associated with obesity. Faecalibacterium prausnitzii is a commensal gut bacterium, the absence of which may be associated with Crohn’s disease. We showed that in our model, A. muciniphila induces stronger effects on the host than F. prausnitzii. We observed that A. muciniphila and propionate affect the expression of genes involved in host lipid metabolism and epigenetic activation or silencing of gene expression. We demonstrated that organoids provide a powerful tool for host-microbe interaction studies.Sabina LukovacClara BelzerLinette PellisBart J. KeijserWillem M. de VosRoy C. MontijnGuus RoeselersAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 4 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Sabina Lukovac Clara Belzer Linette Pellis Bart J. Keijser Willem M. de Vos Roy C. Montijn Guus Roeselers Differential Modulation by <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and <named-content content-type="genus-species">Faecalibacterium prausnitzii</named-content> of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids
description	ABSTRACT The gut microbiota is essential for numerous aspects of human health. However, the underlying mechanisms of many host-microbiota interactions remain unclear. The aim of this study was to characterize effects of the microbiota on host epithelium using a novel ex vivo model based on mouse ileal organoids. We have explored the transcriptional response of organoids upon exposure to short-chain fatty acids (SCFAs) and products generated by two abundant microbiota constituents, Akkermansia muciniphila and Faecalibacterium prausnitzii. We observed that A. muciniphila metabolites affect various transcription factors and genes involved in cellular lipid metabolism and growth, supporting previous in vivo findings. Contrastingly, F. prausnitzii products exerted only weak effects on host transcription. Additionally, A. muciniphila and its metabolite propionate modulated expression of Fiaf, Gpr43, histone deacetylases (HDACs), and peroxisome proliferator-activated receptor gamma (Pparγ), important regulators of transcription factor regulation, cell cycle control, lipolysis, and satiety. This work illustrates that specific bacteria and their metabolites differentially modulate epithelial transcription in mouse organoids. We demonstrate that intestinal organoids provide a novel and powerful ex vivo model for host-microbiome interaction studies. IMPORTANCE We investigated the influence of the gut microbiota and microbially produced short-chain fatty acids (SCFAs) on gut functioning. Many commensal bacteria in the gut produce SCFAs, particularly butyrate, acetate, and propionate, which have been demonstrated to reduce the risk of gastrointestinal disorders. Organoids—small crypt-villus structures grown from ileal intestinal stem cells—were exposed to SCFAs and two specific gut bacteria. Akkermansia muciniphila, found in the intestinal mucus, was recently shown to have a favorable effect on the disrupted metabolism associated with obesity. Faecalibacterium prausnitzii is a commensal gut bacterium, the absence of which may be associated with Crohn’s disease. We showed that in our model, A. muciniphila induces stronger effects on the host than F. prausnitzii. We observed that A. muciniphila and propionate affect the expression of genes involved in host lipid metabolism and epigenetic activation or silencing of gene expression. We demonstrated that organoids provide a powerful tool for host-microbe interaction studies.
format	article
author	Sabina Lukovac Clara Belzer Linette Pellis Bart J. Keijser Willem M. de Vos Roy C. Montijn Guus Roeselers
author_facet	Sabina Lukovac Clara Belzer Linette Pellis Bart J. Keijser Willem M. de Vos Roy C. Montijn Guus Roeselers
author_sort	Sabina Lukovac
title	Differential Modulation by <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and <named-content content-type="genus-species">Faecalibacterium prausnitzii</named-content> of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids
title_short	Differential Modulation by <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and <named-content content-type="genus-species">Faecalibacterium prausnitzii</named-content> of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids
title_full	Differential Modulation by <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and <named-content content-type="genus-species">Faecalibacterium prausnitzii</named-content> of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids
title_fullStr	Differential Modulation by <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and <named-content content-type="genus-species">Faecalibacterium prausnitzii</named-content> of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids
title_full_unstemmed	Differential Modulation by <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and <named-content content-type="genus-species">Faecalibacterium prausnitzii</named-content> of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids
title_sort	differential modulation by <named-content content-type="genus-species">akkermansia muciniphila</named-content> and <named-content content-type="genus-species">faecalibacterium prausnitzii</named-content> of host peripheral lipid metabolism and histone acetylation in mouse gut organoids
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/f0fac67d694c44dda4c1534155d2c36c
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_version_	1718427557500551168

Differential Modulation by <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and <named-content content-type="genus-species">Faecalibacterium prausnitzii</named-content> of Host Peripheral Lipid Metabolism and Histone Acetylation in Mouse Gut Organoids

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