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Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk

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TLDR
The production of TMAO from dietary phosphatidylcholine is dependent on metabolism by the intestinal microbiota and increased levels are associated with an increased risk of incident major adverse cardiovascular events.
Abstract
Background Recent studies in animals have shown a mechanistic link between intestinal microbial metabolism of the choline moiety in dietary phosphatidylcholine (lecithin) and coronary artery disease through the production of a proatherosclerotic metabolite, trimethylamine-N-oxide (TMAO). We investigated the relationship among intestinal microbiota-dependent metabolism of dietary phosphatidylcholine, TMAO levels, and adverse cardiovascular events in humans. Methods We quantified plasma and urinary levels of TMAO and plasma choline and betaine levels by means of liquid chromatography and online tandem mass spectrometry after a phosphatidylcholine challenge (ingestion of two hard-boiled eggs and deuterium [d9]-labeled phosphatidylcholine) in healthy participants before and after the suppression of intestinal microbiota with oral broad-spectrum antibiotics. We further examined the relationship between fasting plasma levels of TMAO and incident major adverse cardiovascular events (death, myocardial infarction,...

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The Human Intestinal Microbiome in Health and Disease

TL;DR: The large majority of studies on the role of the microbiome in the pathogenesis of disease are correlative and preclinical; several have influenced clinical practice.
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The gut microbiota and host health: a new clinical frontier

TL;DR: The potential of manipulating the gut microbiota in these disorders is assessed, with an examination of the latest and most relevant evidence relating to antibiotics, probiotics, prebiotics, polyphenols and faecal microbiota transplantation.
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Gut microbiota in human metabolic health and disease.

TL;DR: How the gut microbiota and derived microbial compounds may contribute to human metabolic health and to the pathogenesis of common metabolic diseases are discussed, and examples of microbiota-targeted interventions aiming to optimize metabolic health are highlighted.
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Metabolomics: beyond biomarkers and towards mechanisms

TL;DR: Because of the inherent sensitivity of metabolomics, subtle alterations in biological pathways can be detected to provide insight into the mechanisms that underlie various physiological conditions and aberrant processes, including diseases.
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Diet–microbiota interactions as moderators of human metabolism

TL;DR: A body of knowledge is accumulating that points to the gut microbiota as a mediator of dietary impact on the host metabolic status and the prospect of therapeutic interventions such as personalized nutrition.
References
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Journal ArticleDOI

The gut microbiota as an environmental factor that regulates fat storage

TL;DR: In this article, the authors found that conventionalization of adult germ-free C57BL/6 mice with a normal microbiota harvested from the distal intestine (cecum) of conventionally raised animals produces a 60% increase in body fat content and insulin resistance within 14 days despite reduced food intake.
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Metagenomic Analysis of the Human Distal Gut Microbiome

TL;DR: Using metabolic function analyses of identified genes, the human genome is compared with the average content of previously sequenced microbial genomes and humans are superorganisms whose metabolism represents an amalgamation of microbial and human attributes.
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Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

TL;DR: Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.
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Commensal Host-Bacterial Relationships in the Gut

TL;DR: The current genomic revolution offers an unprecedented opportunity to identify the molecular foundations of symbionts and commensals so that the authors can understand how they contribute to their normal physiology and how they can be exploited to develop new therapeutic strategies.
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Innate immunity and intestinal microbiota in the development of Type 1 diabetes

TL;DR: It is found that MyD88 deficiency changes the composition of the distal gut microbiota, and that exposure to the microbiota of specific pathogen-free MyD 88-negative NOD donors attenuates T1D in germ-free NOD recipients.
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