Impaired Intestinal <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice

ABSTRACT Noncaloric artificial sweeteners (NAS) are extensively introduced into commonly consumed drinks and foods worldwide. However, data on the health effects of NAS consumption remain elusive. Saccharin and sucralose have been shown to pass through the human gastrointestinal tract without underg...

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Autores principales:	Zunji Shi, Hehua Lei, Gui Chen, Peihong Yuan, Zheng Cao, Hooi-Leng Ser, Xuehang Zhu, Fang Wu, Caixiang Liu, Manyuan Dong, Yuchen Song, Yangyang Guo, Chuan Chen, Kexin Hu, Yifan Zhu, Xin-an Zeng, Jinlin Zhou, Yujing Lu, Andrew D. Patterson, Limin Zhang
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	microbiome gut-liver axis Akkermansia muciniphila AHR ligands Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/dad310dbc35846e993460fb9a4563b07
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spelling	oai:doaj.org-article:dad310dbc35846e993460fb9a4563b072021-12-02T17:07:26ZImpaired Intestinal <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice10.1128/mSystems.00985-202379-5077https://doaj.org/article/dad310dbc35846e993460fb9a4563b072021-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00985-20https://doaj.org/toc/2379-5077ABSTRACT Noncaloric artificial sweeteners (NAS) are extensively introduced into commonly consumed drinks and foods worldwide. However, data on the health effects of NAS consumption remain elusive. Saccharin and sucralose have been shown to pass through the human gastrointestinal tract without undergoing absorption and metabolism and directly encounter the gut microbiota community. Here, we aimed to identify a novel mechanism linking intestinal Akkermansia muciniphila and the aryl hydrocarbon receptor (AHR) to saccharin/sucralose-induced nonalcoholic fatty liver disease (NAFLD) in mice. Saccharin/sucralose consumption altered the gut microbial community structure, with significant depletion of A. muciniphila abundance in the cecal contents of mice, resulting in disruption of intestinal permeability and a high level of serum lipopolysaccharide, which likely contributed to systemic inflammation and caused NAFLD in mice. Saccharin/sucralose also markedly decreased microbiota-derived AHR ligands and colonic AHR expression, which are closely associated with many metabolic syndromes. Metformin or fructo-oligosaccharide supplementation significantly restored A. muciniphila and AHR ligands in sucralose-consuming mice, consequently ameliorating NAFLD. IMPORTANCE Our findings indicate that the gut-liver signaling axis contributes to saccharin/sucralose consumption-induced NAFLD. Supplementation with metformin or fructo-oligosaccharide is a potential therapeutic strategy for NAFLD treatment. In addition, we also developed a new nutritional strategy by using a natural sweetener (neohesperidin dihydrochalcone [NHDC]) as a substitute for NAS and free sugars.Zunji ShiHehua LeiGui ChenPeihong YuanZheng CaoHooi-Leng SerXuehang ZhuFang WuCaixiang LiuManyuan DongYuchen SongYangyang GuoChuan ChenKexin HuYifan ZhuXin-an ZengJinlin ZhouYujing LuAndrew D. PattersonLimin ZhangAmerican Society for Microbiologyarticlemicrobiomegut-liver axisAkkermansia muciniphilaAHR ligandsMicrobiologyQR1-502ENmSystems, Vol 6, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microbiome gut-liver axis Akkermansia muciniphila AHR ligands Microbiology QR1-502
spellingShingle	microbiome gut-liver axis Akkermansia muciniphila AHR ligands Microbiology QR1-502 Zunji Shi Hehua Lei Gui Chen Peihong Yuan Zheng Cao Hooi-Leng Ser Xuehang Zhu Fang Wu Caixiang Liu Manyuan Dong Yuchen Song Yangyang Guo Chuan Chen Kexin Hu Yifan Zhu Xin-an Zeng Jinlin Zhou Yujing Lu Andrew D. Patterson Limin Zhang Impaired Intestinal <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice
description	ABSTRACT Noncaloric artificial sweeteners (NAS) are extensively introduced into commonly consumed drinks and foods worldwide. However, data on the health effects of NAS consumption remain elusive. Saccharin and sucralose have been shown to pass through the human gastrointestinal tract without undergoing absorption and metabolism and directly encounter the gut microbiota community. Here, we aimed to identify a novel mechanism linking intestinal Akkermansia muciniphila and the aryl hydrocarbon receptor (AHR) to saccharin/sucralose-induced nonalcoholic fatty liver disease (NAFLD) in mice. Saccharin/sucralose consumption altered the gut microbial community structure, with significant depletion of A. muciniphila abundance in the cecal contents of mice, resulting in disruption of intestinal permeability and a high level of serum lipopolysaccharide, which likely contributed to systemic inflammation and caused NAFLD in mice. Saccharin/sucralose also markedly decreased microbiota-derived AHR ligands and colonic AHR expression, which are closely associated with many metabolic syndromes. Metformin or fructo-oligosaccharide supplementation significantly restored A. muciniphila and AHR ligands in sucralose-consuming mice, consequently ameliorating NAFLD. IMPORTANCE Our findings indicate that the gut-liver signaling axis contributes to saccharin/sucralose consumption-induced NAFLD. Supplementation with metformin or fructo-oligosaccharide is a potential therapeutic strategy for NAFLD treatment. In addition, we also developed a new nutritional strategy by using a natural sweetener (neohesperidin dihydrochalcone [NHDC]) as a substitute for NAS and free sugars.
format	article
author	Zunji Shi Hehua Lei Gui Chen Peihong Yuan Zheng Cao Hooi-Leng Ser Xuehang Zhu Fang Wu Caixiang Liu Manyuan Dong Yuchen Song Yangyang Guo Chuan Chen Kexin Hu Yifan Zhu Xin-an Zeng Jinlin Zhou Yujing Lu Andrew D. Patterson Limin Zhang
author_facet	Zunji Shi Hehua Lei Gui Chen Peihong Yuan Zheng Cao Hooi-Leng Ser Xuehang Zhu Fang Wu Caixiang Liu Manyuan Dong Yuchen Song Yangyang Guo Chuan Chen Kexin Hu Yifan Zhu Xin-an Zeng Jinlin Zhou Yujing Lu Andrew D. Patterson Limin Zhang
author_sort	Zunji Shi
title	Impaired Intestinal <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice
title_short	Impaired Intestinal <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice
title_full	Impaired Intestinal <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice
title_fullStr	Impaired Intestinal <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice
title_full_unstemmed	Impaired Intestinal <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice
title_sort	impaired intestinal <named-content content-type="genus-species">akkermansia muciniphila</named-content> and aryl hydrocarbon receptor ligands contribute to nonalcoholic fatty liver disease in mice
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/dad310dbc35846e993460fb9a4563b07
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Impaired Intestinal <named-content content-type="genus-species">Akkermansia muciniphila</named-content> and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice

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