Effect of a High-Fat Diet on the Small-Intestinal Environment and Mucosal Integrity in the Gut-Liver Axis

Although high-fat diet (HFD)-related dysbiosis is involved in the development of steatohepatitis, its pathophysiology especially in the small intestine remains unclear. We comprehensively investigated not only the liver pathology but also the microbiome profile, mucosal integrity and luminal environ...

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Autores principales:	Takashi Nakanishi, Hirokazu Fukui, Xuan Wang, Shin Nishiumi, Haruka Yokota, Yutaka Makizaki, Yoshiki Tanaka, Hiroshi Ohno, Toshihiko Tomita, Tadayuki Oshima, Hiroto Miwa
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	high-fat diet small intestine microbiome bile acid barrier Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f048463681c14ac89cf39d525ccd77fb
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spelling	oai:doaj.org-article:f048463681c14ac89cf39d525ccd77fb2021-11-25T17:12:16ZEffect of a High-Fat Diet on the Small-Intestinal Environment and Mucosal Integrity in the Gut-Liver Axis10.3390/cells101131682073-4409https://doaj.org/article/f048463681c14ac89cf39d525ccd77fb2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3168https://doaj.org/toc/2073-4409Although high-fat diet (HFD)-related dysbiosis is involved in the development of steatohepatitis, its pathophysiology especially in the small intestine remains unclear. We comprehensively investigated not only the liver pathology but also the microbiome profile, mucosal integrity and luminal environment in the small intestine of mice with HFD-induced obesity. C57BL/6J mice were fed either a normal diet or an HFD, and their small-intestinal contents were subjected to microbial 16S rDNA analysis. Intestinal mucosal permeability was evaluated by FITC-dextran assay. The levels of bile acids in the small-intestinal contents were measured by liquid chromatography/mass spectrometry. The expression of tight junction molecules, antimicrobial peptides, lipopolysaccharide and macrophage marker F4/80 in the small intestine and/or liver was examined by real-time RT-PCR and immunohistochemistry. The abundance of <i>Lactobacillus</i> was markedly increased and that of <i>Clostridium</i> was drastically decreased in the small intestine of mice fed the HFD. The level of conjugated taurocholic acid was significantly increased and those of deconjugated cholic acid/secondary bile acids were conversely decreased in the small-intestinal contents. The expression of occludin, antimicrobial Reg IIIβ/γ and IL-22 was significantly decreased in the small intestine of HFD-fed mice, and the intestinal permeability was significantly accelerated. Infiltration of lipopolysaccharide was significantly increased in not only the small-intestinal mucosa but also the liver of HFD-fed mice, and fat drops were apparently accumulated in the liver. Pathophysiological alteration of the luminal environment in the small intestine resulting from a HFD is closely associated with minimal inflammation involving the gut-liver axis through disturbance of small-intestinal mucosal integrity.Takashi NakanishiHirokazu FukuiXuan WangShin NishiumiHaruka YokotaYutaka MakizakiYoshiki TanakaHiroshi OhnoToshihiko TomitaTadayuki OshimaHiroto MiwaMDPI AGarticlehigh-fat dietsmall intestinemicrobiomebile acidbarrierBiology (General)QH301-705.5ENCells, Vol 10, Iss 3168, p 3168 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	high-fat diet small intestine microbiome bile acid barrier Biology (General) QH301-705.5
spellingShingle	high-fat diet small intestine microbiome bile acid barrier Biology (General) QH301-705.5 Takashi Nakanishi Hirokazu Fukui Xuan Wang Shin Nishiumi Haruka Yokota Yutaka Makizaki Yoshiki Tanaka Hiroshi Ohno Toshihiko Tomita Tadayuki Oshima Hiroto Miwa Effect of a High-Fat Diet on the Small-Intestinal Environment and Mucosal Integrity in the Gut-Liver Axis
description	Although high-fat diet (HFD)-related dysbiosis is involved in the development of steatohepatitis, its pathophysiology especially in the small intestine remains unclear. We comprehensively investigated not only the liver pathology but also the microbiome profile, mucosal integrity and luminal environment in the small intestine of mice with HFD-induced obesity. C57BL/6J mice were fed either a normal diet or an HFD, and their small-intestinal contents were subjected to microbial 16S rDNA analysis. Intestinal mucosal permeability was evaluated by FITC-dextran assay. The levels of bile acids in the small-intestinal contents were measured by liquid chromatography/mass spectrometry. The expression of tight junction molecules, antimicrobial peptides, lipopolysaccharide and macrophage marker F4/80 in the small intestine and/or liver was examined by real-time RT-PCR and immunohistochemistry. The abundance of <i>Lactobacillus</i> was markedly increased and that of <i>Clostridium</i> was drastically decreased in the small intestine of mice fed the HFD. The level of conjugated taurocholic acid was significantly increased and those of deconjugated cholic acid/secondary bile acids were conversely decreased in the small-intestinal contents. The expression of occludin, antimicrobial Reg IIIβ/γ and IL-22 was significantly decreased in the small intestine of HFD-fed mice, and the intestinal permeability was significantly accelerated. Infiltration of lipopolysaccharide was significantly increased in not only the small-intestinal mucosa but also the liver of HFD-fed mice, and fat drops were apparently accumulated in the liver. Pathophysiological alteration of the luminal environment in the small intestine resulting from a HFD is closely associated with minimal inflammation involving the gut-liver axis through disturbance of small-intestinal mucosal integrity.
format	article
author	Takashi Nakanishi Hirokazu Fukui Xuan Wang Shin Nishiumi Haruka Yokota Yutaka Makizaki Yoshiki Tanaka Hiroshi Ohno Toshihiko Tomita Tadayuki Oshima Hiroto Miwa
author_facet	Takashi Nakanishi Hirokazu Fukui Xuan Wang Shin Nishiumi Haruka Yokota Yutaka Makizaki Yoshiki Tanaka Hiroshi Ohno Toshihiko Tomita Tadayuki Oshima Hiroto Miwa
author_sort	Takashi Nakanishi
title	Effect of a High-Fat Diet on the Small-Intestinal Environment and Mucosal Integrity in the Gut-Liver Axis
title_short	Effect of a High-Fat Diet on the Small-Intestinal Environment and Mucosal Integrity in the Gut-Liver Axis
title_full	Effect of a High-Fat Diet on the Small-Intestinal Environment and Mucosal Integrity in the Gut-Liver Axis
title_fullStr	Effect of a High-Fat Diet on the Small-Intestinal Environment and Mucosal Integrity in the Gut-Liver Axis
title_full_unstemmed	Effect of a High-Fat Diet on the Small-Intestinal Environment and Mucosal Integrity in the Gut-Liver Axis
title_sort	effect of a high-fat diet on the small-intestinal environment and mucosal integrity in the gut-liver axis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f048463681c14ac89cf39d525ccd77fb
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Effect of a High-Fat Diet on the Small-Intestinal Environment and Mucosal Integrity in the Gut-Liver Axis

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