FMO3 and its metabolite TMAO contribute to the formation of gallstones

Chen, Yaoyao; Weng, Zhenkun; Lei, Qian; Shao, Wentao; Guo, Wenhui; Chen, Chaobo; Jiao, Long R.; Wang, Qihan; Lu, Qishao; Sun, Haidong; Gu, Aihua; Hu, Hai; Jiang, Zhaoyan

doi:10.1016/j.bbadis.2019.06.016

Cited by 40 publications

(38 citation statements)

References 43 publications

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“…Our previous study found that steroid hormone biosynthesis pathway is disturbed in SHS individuals [16], which indicates that the upregulation of ABCG8 might be associated with the disorder of steroid hormone biosynthesis in SHS individuals. Chen and colleagues have observed that trimethylamine-N-oxide, a metabolite produced by gut microbiota, is associated with increased ABCG8 expression [51]. In addition, Zhu et al has proved that intestinal microbiota, Enterococcus faecalis, increase the expression of ABCG8 [52].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic Characteristics of Suboptimal Health Status: Potential Utility of Novel Biomarkers for Predictive, Preventive, and Personalized Medicine Strategy

Wang

Tian

Zhang

et al. 2021

Preprint

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Background The early diagnosis of Suboptimal Health Status (SHS) creates a window opportunity for the predictive, preventive, and personalized medicine (PPPM) of chronic diseases. Previous studies have observed the alterations in several mRNA levels in SHS individuals. As a promising “omics” technology offering comprehension of genome structure and function at RNA level, transcriptome profiling can provide innovative molecular biomarkers for the predictive diagnosis and targeted prevention of SHS. Methods To explore the potential diagnostic biomarkers, biological functions, and signaling pathways involved in SHS, an RNA sequencing (RNA-Seq)-based transcriptome analysis was firstly conducted on buffy coat samples collected from 30 participants with SHS and 30 age- and sex-matched healthy controls. Results Transcriptome analysis identified a total of 46 differentially expressed genes, in which 22 transcripts were significantly increased and 24 transcripts were decreased in the SHS group. A total of 23 transcripts was selected as candidate diagnostic biomarkers for SHS. Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that several biological processes were related to SHS, such as ATP-binding cassette (ABC) transporter and neurodegeneration. Protein-protein interaction (PPI) network analysis identified 10 hub gene related to SHS, including GJA1, TWIST2, KRT1, TUBB3, AMHR2, BMP10, MT3, BMPER, NTM and TMEM98. A transcriptome diagnosis model can distinguish SHS individuals from the healthy controls with a sensitivity of 83.3% (95% Confidence Interval (CI): 73.9%-92.7%), a specificity of 90.0% (95% CI: 82.4%-97.6%), and an area under the receiver operating characteristic curve of 0.938 (95% CI: 0.882–0.994). Conclusion Blood transcripts are potentially objective biomarkers for the SHS diagnosis. These findings determine the potential utility of SHS-related transcriptomic biomarkers for PPPM of chronic diseases.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic Characteristics of Suboptimal Health Status: Potential Utility of Novel Biomarkers for Predictive, Preventive, and Personalized Medicine Strategy

Wang

Tian

Zhang

et al. 2021

Preprint

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“…Convincing antibiotic studies further validate the primary role of the intestinal microbiome in TMAO production and accumulation. When the microbiome is intact and diets are supplemented with substrates, circulating TMAO levels increase predictably [ 36 , 91 ]. When the microbiome is absent, as in gnotobiotic or antibiotic treated animals, TMAO levels and its subsequent effects are blocked [ 42 , 91 , 115 , 116 , 117 ].…”

Section: Tmao Accumulation In Serummentioning

confidence: 99%

“…Clinical TMAO effects are most closely tied to atherosclerotic phenotypes, although there is some debate [ 30 , 31 ]. Resent TMAO research has recently expanded to include other chronic metabolic diseases [ 20 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ]. Over-nutrition related metabolic phenotypes including insulin resistance, type 2 diabetes (T2D), obesity, metabolic syndrome, and chronic kidney disease (CKD) which are already associated with CVD have been linked to TMAO [ 39 , 44 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ].…”

Section: Introductionmentioning

confidence: 99%

The Accumulation and Molecular Effects of Trimethylamine N-Oxide on Metabolic Tissues: It’s Not All Bad

2021

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Since elevated serum levels of trimethylamine N-oxide (TMAO) were first associated with increased risk of cardiovascular disease (CVD), TMAO research among chronic diseases has grown exponentially. We now know that serum TMAO accumulation begins with dietary choline metabolism across the microbiome-liver-kidney axis, which is typically dysregulated during pathogenesis. While CVD research links TMAO to atherosclerotic mechanisms in vascular tissue, its molecular effects on metabolic tissues are unclear. Here we report the current standing of TMAO research in metabolic disease contexts across relevant tissues including the liver, kidney, brain, adipose, and muscle. Since poor blood glucose management is a hallmark of metabolic diseases, we also explore the variable TMAO effects on insulin resistance and insulin production. Among metabolic tissues, hepatic TMAO research is the most common, whereas its effects on other tissues including the insulin producing pancreatic β-cells are largely unexplored. Studies on diseases including obesity, diabetes, liver diseases, chronic kidney disease, and cognitive diseases reveal that TMAO effects are unique under pathologic conditions compared to healthy controls. We conclude that molecular TMAO effects are highly context-dependent and call for further research to clarify the deleterious and beneficial molecular effects observed in metabolic disease research.

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“…Recently, in Asian countries, this biliary tract disease has been rapidly increasing due to changes in dietary habits and life style, although it is highly prevalent in people from Western countries compared to Asian countries (Chen et al, 2019). It is well known that cholesterol gallstone formation is mainly due to the imbalance of bile components, which is affected by hypersecretion and accumulation of cholesterol (Song et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Cholesterol gallstone disease is one of the most common conditions in the gastrointestinal tract, which is caused by the complex interaction of multiple genetic and environmental factors that contribute to the gallstone formation ( Chuang et al, 2012 ). Recently, in Asian countries, this biliary tract disease has been rapidly increasing due to changes in dietary habits and life style, although it is highly prevalent in people from Western countries compared to Asian countries ( Chen et al, 2019 ). It is well known that cholesterol gallstone formation is mainly due to the imbalance of bile components, which is affected by hypersecretion and accumulation of cholesterol ( Song et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Prevention of Cholesterol Gallstone Formation by Lactobacillus acidophilus ATCC 43121 and Lactobacillus fermentum MF27 in Lithogenic Diet-Induced Mice

Oh¹,

Kim²,

Lee³

et al. 2021

Food Sci Anim Resour

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The objective of this study was to evaluate the effects of Lactobacillus acidophilus ATCC 43121 and L. fermentum MF27 on biochemical indices in the serum, cholesterol metabolism in the liver and mucin expression in the gallbladder in lithogenic diet (LD)induced C57BL/6 mice to determine the preventive effects of lactobacilli on gallstone formation. By the end of 4 wk of the experimental period, mice fed on a LD with high-fat and high-cholesterol exhibited higher levels of total and low-density lipoprotein cholesterol in the serum compared to mice fed on control diet or LD with Lactobacillus acidophilus ATCC 43121 (LD+P1; p<0.05). Cholesterol-lowering effects observed in the LD+P1 and LD with L. fermentum MF27 (LD+P2) groups were associated with reduced expression of 3-hydroxy-3methylglutaryl coenzyme A reductase in the liver compared to the LD group (p<0.05). Furthermore, expression of the gel-forming mucin, including MUC5AB and MUC5B, was suppressed in the LD+P1 and LD+P2 groups compared to the LD group (p<0.05). Therefore, steady intake of both L. acidophilus ATCC 43121 and L. fermentum MF27 may have the ability to prevent the formation of cholesterol gallstones in LD-induced C57BL/6 mice.

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FMO3 and its metabolite TMAO contribute to the formation of gallstones

Cited by 40 publications

References 43 publications

Transcriptomic Characteristics of Suboptimal Health Status: Potential Utility of Novel Biomarkers for Predictive, Preventive, and Personalized Medicine Strategy

Transcriptomic Characteristics of Suboptimal Health Status: Potential Utility of Novel Biomarkers for Predictive, Preventive, and Personalized Medicine Strategy

The Accumulation and Molecular Effects of Trimethylamine N-Oxide on Metabolic Tissues: It’s Not All Bad

Prevention of Cholesterol Gallstone Formation by Lactobacillus acidophilus ATCC 43121 and Lactobacillus fermentum MF27 in Lithogenic Diet-Induced Mice

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