scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Impaired Intestinal Akkermansia muciniphila and Aryl Hydrocarbon Receptor Ligands Contribute to Nonalcoholic Fatty Liver Disease in Mice.

TL;DR: 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.
Citations
More filters
Journal ArticleDOI
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.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by hepatic accumulation of excess lipids. T cells are commonly classified into various subsets based on their surface markers including T cell receptors, type of antigen presentation and pathophysiological functions. Several studies have implicated various T cell subsets and natural killer (NK) cells in the progression of NAFLD. While NK cells are mainly components of the innate hepatic immune system, the majority of T cell subsets can be part of both the adaptive and innate systems. Several studies have reported that various stages of NAFLD are accompanied by the accumulation of distinct T cell subsets and NK cells with different functions and phenotypes observed usually resulting in proinflammatory effects. More importantly, the overall stimulation of the intrahepatic T cell subsets is directly influenced by the homeostasis of the gut microbiota. Similarly, NK cells have been found to accumulate in the liver in response to pathogens and tumors. In this review, we 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.

12 citations

Journal ArticleDOI
01 Jun 2021-Toxics
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.
Abstract: 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 [...].

12 citations

Journal ArticleDOI
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.

10 citations

Journal ArticleDOI
14 Jul 2021
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.
Abstract: Akkermansia muciniphila, a potential probiotic, has been proven to lessen the effects of several diseases. As established, the relative abundance of Akkermansia is positively correlated with tryptophan metabolism. However, the reciprocal interaction between tryptophan and Akkemansia is still unclear. Herein, for the first time, the possible effects of tryptophan and its derived metabolites on A. muciniphila were preliminarily investigated, including growth, physiological function, and metabolism. Obtained results suggested that 0.4 g/L of tryptophan treatment could significantly promote the growth of A. muciniphila. Notably, when grown in BHI with 0.8 g/L of tryptophan, the hydrophobicity and adhesion of A. muciniphila were significantly improved, potentially due to the increase in the rate of cell division. Furthermore, A. muciniphila metabolized tryptophan to indole, indole-3-acetic acid, indole-3-carboxaldehyde, and indole-3-lactic acid. Indoles produced by gut microbiota could significantly promote the growth of A. muciniphila. These results could provide a valuable reference for future research on the relationship between tryptophan metabolism and A. muciniphila.

9 citations

Journal ArticleDOI
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.

7 citations

References
More filters
Journal ArticleDOI
TL;DR: Substantial insight is provided into the intricate mechanisms of bacterial regulation of the cross-talk between the host and gut microbiota and provides a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.
Abstract: Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.

3,263 citations

Journal ArticleDOI
05 Jan 2018-Science
TL;DR: It is found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition, and Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer.
Abstract: Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so. Metagenomics of patient stool samples at diagnosis revealed correlations between clinical responses to ICIs and the relative abundance of Akkermansia muciniphila Oral supplementation with A. muciniphila after FMT with nonresponder feces restored the efficacy of PD-1 blockade in an interleukin-12-dependent manner by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into mouse tumor beds.

3,258 citations

Journal ArticleDOI
17 Nov 2016-Cell
TL;DR: Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium.

1,689 citations

Journal ArticleDOI
04 Sep 2014-Nature
TL;DR: The gut microbiome in liver cirrhosis is characterized by comparing 98 patients and 83 healthy control individuals and on the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort, suggesting microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases.
Abstract: Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate < 0.0001) and can be grouped into 66 clusters representing cognate bacterial species; 28 are enriched in patients and 38 in control individuals. Most (54%) of the patient-enriched, taxonomically assigned species are of buccal origin, suggesting an invasion of the gut from the mouth in liver cirrhosis. Biomarkers specific to liver cirrhosis at gene and function levels are revealed by a comparison with those for type 2 diabetes and inflammatory bowel disease. On the basis of only 15 biomarkers, a highly accurate patient discrimination index is created and validated on an independent cohort. Thus microbiota-targeted biomarkers may be a powerful tool for diagnosis of different diseases. Invasion of the gut by oral bacteria in liver cirrhosis. Previous work has revealed an association between liver complications such as cirrhosis and the gut microbiome. Lanjuan Li and colleagues undertook a microbiome-wide association study of stool samples from 98 liver cirrhosis patients and 83 healthy controls. Quantitative metagenomics analysis revealed 75,245 genes that were significantly different in abundance between the two groups, many of which could be grouped into 66 clusters that represent cognate bacterial species. Of these, 28 species were enriched in liver cirrhosis patients and most were of buccal origin (mostly Veillonella and streptococci). The identified markers were unique liver cirrhosis-specific genes and the authors identify a set of just 15 of these genes that could form the basis of a highly accurate discrimination index that could be used as a diagnostic tool.

1,542 citations

Journal ArticleDOI
22 Aug 2013-Immunity
TL;DR: A metabolic pathway whereby Trp metabolites from the microbiota balance mucosal reactivity in mice is described, whereby highly adaptive lactobacilli are expanded and produce an aryl hydrocarbon receptor (AhR) ligand-indole-3-aldehyde-that contributes to AhR-dependent Il22 transcription.

1,540 citations

Related Papers (5)