Gut microbial metabolite TMAO contributes to renal dysfunction in a mouse model of diet-induced obesity

Sun, Guangping; Yin, Zhongmin; Liu, Naiquan; Bian, Xue; Yu, Rui; Su, Xiaoxiao; Zhang, Beiru; Wang, Yanqiu

doi:10.1016/j.bbrc.2017.09.108

Cited by 111 publications

(96 citation statements)

References 34 publications

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“…This evidence proves that gut microbiota affects the RAAS function and related metabolites [44]. In addition, the hypertensive phenotype was transferred via fecal transplantation into GF mice repeatedly, proving an influence of the gut microbiota on blood pressure [44]. Various approaches suggest that microbiota metabolites interact with receptors in the brain and vascular walls, as well as affecting immune cells and changing blood pressure [45,46].…”

Section: Introductionmentioning

confidence: 84%

“…The study compared wild-type, conventionally raised mice with GF mice, and demonstrated that the altered metabolites detected in CONV-R mice showed no significant changes in the GF group [41]. This evidence proves that gut microbiota affects the RAAS function and related metabolites [44]. In addition, the hypertensive phenotype was transferred via fecal transplantation into GF mice repeatedly, proving an influence of the gut microbiota on blood pressure [44].…”

Section: Introductionmentioning

confidence: 89%

“…Therefore, flavin-containing monooxygenases in the liver oxidize TMA to TMAO [84], which is linked to increased insulin resistance, as higher TMAO blood levels were noted in diabetes [85]. In addition, TMAO affects chronically infused angiotensin II signaling, contributing to prolonged hypertension [86] and increases the risk of CVD and vascular wall inflammation [44,87].…”

Section: Patterns and Metabolites From The Gut Microbiota As Drivers mentioning

confidence: 99%

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The Gut Microbiota in Cardiovascular Disease and Arterial Thrombosis

et al. 2019

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The gut microbiota has emerged as a contributing factor in the development of atherosclerosis and arterial thrombosis. Metabolites from the gut microbiota, such as trimethylamine N-oxide and short chain fatty acids, were identified as messengers that induce cell type-specific signaling mechanisms and immune reactions in the host vasculature, impacting the development of cardiovascular diseases. In addition, microbial-associated molecular patterns drive atherogenesis and the microbiota was recently demonstrated to promote arterial thrombosis through Toll-like receptor signaling. Furthermore, by the use of germ-free mouse models, the presence of a gut microbiota was shown to influence the synthesis of endothelial adhesion molecules. Hence, the gut microbiota is increasingly being recognized as an influencing factor of arterial thrombosis and attempts of dietary pre-or probiotic modulation of the commensal microbiota, to reduce cardiovascular risk, are becoming increasingly significant.

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Section: Introductionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 89%

Section: Patterns and Metabolites From The Gut Microbiota As Drivers mentioning

confidence: 99%

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The Gut Microbiota in Cardiovascular Disease and Arterial Thrombosis

et al. 2019

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“…Previously, a diet resembling a western diet high in saturated fats and sugar was shown to increase plasma TMAO concentrations in mice compared to the consumption of a standard diet [26]. Likewise, high-fat diets were found to increase postprandial plasma TMAO concentrations in both mice and human [27,28]. It was suggested that a high-fat diet could possibly increase TMAO concentrations through alterations in gut microbial composition and function [26][27][28].…”

Section: Background Diet Affects Urinary Tmao Excretion Following Redmentioning

confidence: 99%

“…Likewise, high-fat diets were found to increase postprandial plasma TMAO concentrations in both mice and human [27,28]. It was suggested that a high-fat diet could possibly increase TMAO concentrations through alterations in gut microbial composition and function [26][27][28]. The higher fat content in the western background diet compared to the prudent background diet might have contributed to increased TMAO formation through alterations of the gut microbiota.…”

Section: Background Diet Affects Urinary Tmao Excretion Following Redmentioning

confidence: 99%

Background Diet Influences TMAO Concentrations Associated with Red Meat Intake without Influencing Apparent Hepatic TMAO-Related Activity in a Porcine Model

et al. 2020

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Red meat has been associated with an increased cardiovascular disease (CVD) risk, possibly through gut microbial-derived trimethylamine-N-oxide (TMAO). However, previous reports are conflicting, and influences from the background diet may modulate the impact of meat consumption. This study investigated the effect of red and white meat intake combined with two different background diets on urinary TMAO concentration and its association with the colon microbiome in addition to apparent hepatic TMAO-related activity. For 4 weeks, 32 pigs were fed chicken or red and processed meat combined with a prudent or western background diet. 1 H NMR-based metabolomics analysis was conducted on urine samples and hepatic Mrna expression of TMAO-related genes determined. Lower urinary TMAO concentrations were observed after intake of red and processed meat when consumed with a prudent compared to a western background diet. In addition, correlation analyses between urinary TMAO concentrations and relative abundance of colon bacterial groups suggested an association between TMAO and specific bacterial taxa. Diet did not affect the hepatic Mrna expression of genes related to TMAO formation. The results suggest that meat-induced TMAO formation is regulated by mechanisms other than alterations at the hepatic gene expression level, possibly involving modulations of the gut microbiota.

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Association of TrimethylamineN-Oxide and Related Metabolites in Plasma and Incident Type 2 Diabetes

et al. 2021

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IMPORTANCE Although rodent studies suggest that trimethylamine N-oxide (TMAO) influences glucose homeostasis and risk of type 2 diabetes, evidence in humans is limited. OBJECTIVE To examine the associations of serial measures of plasma TMAO and related metabolite concentrations with incident type 2 diabetes, fasting plasma insulin and glucose levels, and the Gutt insulin sensitivity index (ISI). DESIGN, SETTING, AND PARTICIPANTS This prospective cohort design assessed the association of plasma TMAO and related metabolite concentrations with diabetes outcome, whereas a crosssectional design assessed the association with insulin and glucose levels and Gutt ISI. The participants were a cohort of older US adults from the Cardiovascular Health Study (CHS). Data from

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Gut microbial metabolite TMAO contributes to renal dysfunction in a mouse model of diet-induced obesity

Cited by 111 publications

References 34 publications

The Gut Microbiota in Cardiovascular Disease and Arterial Thrombosis

The Gut Microbiota in Cardiovascular Disease and Arterial Thrombosis

Background Diet Influences TMAO Concentrations Associated with Red Meat Intake without Influencing Apparent Hepatic TMAO-Related Activity in a Porcine Model

Association of TrimethylamineN-Oxide and Related Metabolites in Plasma and Incident Type 2 Diabetes

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