Impaired Intestinal Akkermansia muciniphila and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice.
Zunji Shi,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,Yu-Jing Lu,Andrew D. Patterson,Limin Zhang +20 more
- Vol. 6, Iss: 1
TLDR
In this article, the authors identify a mechanism linking intestinal Akkermansia muciniphila and the aryl hydrocarbon receptor (AHR) to saccharin/sucralose-induced nonalcoholic fatty liver disease (NAFLD) 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 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.read more
Citations
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Journal ArticleDOI
T Cell Subsets and Natural Killer Cells in the Pathogenesis of Nonalcoholic Fatty Liver Disease
Yoseph Asmelash Gebru,Haripriya Gupta,Hyeong Seop Kim,Jung A Eom,Goo Hyun Kwon,Eun-Ju Park,Jin-Ju Jeong,Sung-Min Won,Satya Priya Sharma,Raja Ganesan,Dong Joon Kim,Ki Tae Suk +11 more
TL;DR: In this article, the authors discussed the nature and pathophysiological roles of T cell subsets including γδ T cells, NKT cells, Mucosal-associated invariant T (MAIT) cells as well as NK cells in NAFLD.
Journal ArticleDOI
Gut Microbiota Manipulation to Mitigate the Detrimental Effects of Environmental Pollutants
TL;DR: The ecotoxicology and human health risks of environmental pollutants are creating global concern, especially in the context of the prevalent and severe contamination of environmental abiotic and biotic compartments as discussed by the authors.
Journal ArticleDOI
Proteomics and metabolic phenotyping define principal roles for the aryl hydrocarbon receptor in mouse liver
Jian Jin,Jian Jin,Banrida Wahlang,Monika Thapa,Kimberly Z. Head,Josiah E. Hardesty,Sudhir Srivastava,Sudhir Srivastava,Michael L. Merchant,Shesh N. Rai,Russell A. Prough,Matthew C. Cave +11 more
TL;DR: In this article, aryl hydrocarbon receptor (AHR) biology, metabolic phenotyping and liver proteomics were performed in mice following ligand-activation or whole-body genetic ablation of this receptor.
Journal ArticleDOI
Dose-Dependent Beneficial Effects of Tryptophan and Its Derived Metabolites on Akkermansia In Vitro: A Preliminary Prospective Study
TL;DR: In this article, the possible effects of tryptophan and its derived metabolites on Akkermansia muciniphila were preliminarily investigated, including growth, physiological function, and metabolism.
Journal ArticleDOI
Alteration of fecal microbiome and metabolome by mung bean coat improves diet-induced non-alcoholic fatty liver disease in mice
TL;DR: Zhang et al. as discussed by the authors investigated whether MBC, which is rich in dietary fiber and phytochemicals, can protect against HFD-induced hepatic steatosis in mice via targeting gut microbiota and its metabolites.
References
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Christopher D. Gardner,Judith Wylie-Rosett,Samuel S. Gidding,Lyn M. Steffen,Rachel K. Johnson,Diane Reader,Alice H. Lichtenstein +6 more
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Gut Microbiome Response to Sucralose and Its Potential Role in Inducing Liver Inflammation in Mice.
TL;DR: Enrichment of bacterial pro-inflammatory genes and disruption in fecal metabolites suggest that 6-month sucralose consumption at the human acceptable daily intake (ADI) may increase the risk of developing tissue inflammation by disrupting the gut microbiota, which is supported by elevated pro- inflammatory gene expression in the liver of Sucralose-treated mice.
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AHR Activation Is Protective against Colitis Driven by T Cells in Humanized Mice.
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