The Microbial Metabolite Trimethylamine N-Oxide Links Vascular Dysfunctions and the Autoimmune Disease Rheumatoid Arthritis

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Abstract

Diet and microbiota each have a direct impact on many chronic, inflammatory, and metabolic diseases. As the field develops, a new perspective is emerging. The effects of diet may depend on the microbiota composition of the intestine. A diet that is rich in choline, red meat, dairy, or egg may promote the growth, or change the composition, of microbial species. The microbiota, in turn, may produce metabolites that increase the risk of cardiovascular disease. This article reviews our current understanding of the effects of the molecule trimethylamine- N-oxide (TMAO) obtained from food or produced by the microbiota. We review the mechanisms of actions of TMAO, and studies that associate it with cardiovascular and chronic kidney diseases. We introduce a novel concept: TMAO is one among a group of selective uremic toxins that may rise to high levels in the circulation or accumulate in various organs. Based on this information, we evaluate how TMAO may harm, by exacerbating inflammation, or may protect, by attenuating amyloid formation, in autoimmune diseases such as rheumatoid arthritis.

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Most cited references 106

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Formation of propionate and butyrate by the human colonic microbiota

Petra Louis, Harry J. Flint (2017)

The human gut microbiota ferments dietary non-digestible carbohydrates into short-chain fatty acids (SCFA). These microbial products are utilized by the host and propionate and butyrate in particular exert a range of health-promoting functions. Here an overview of the metabolic pathways utilized by gut microbes to produce these two SCFA from dietary carbohydrates and from amino acids resulting from protein breakdown is provided. This overview emphasizes the important role played by cross-feeding of intermediary metabolites (in particular lactate, succinate and 1,2-propanediol) between different gut bacteria. The ecophysiology, including growth requirements and responses to environmental factors, of major propionate and butyrate producing bacteria are discussed in relation to dietary modulation of these metabolites. A detailed understanding of SCFA metabolism by the gut microbiota is necessary to underpin effective strategies to optimize SCFA supply to the host.

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Enterotypes in the landscape of gut microbial community composition

Paul Costea, Falk Hildebrand, Arumugam Manimozhiyan … (2018)

Population stratification is a useful approach towards a better understanding of complex biological problems in human health and well-being. The proposal that such stratification applies to the human gut microbiome, in the form of distinct community composition types, termed “enterotypes”, was met with both excitement and controversy. In view of accumulated data and re-analyses since the original work, we revisit the enterotype concept, discuss different methods of dividing up the landscape of possible microbiome configurations, and put these concepts into a functional, ecological and medical context. As enterotypes are of use in describing the gut microbial community landscape and may become relevant in clinical practice, we aim to reconcile differing views and encourage a balanced application of the concept.

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Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide

Kymberleigh A. Romano, Eugenio I. Vivas, Daniel Amador-Noguez … (2015)

ABSTRACT Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which upon absorption by the host is converted in the liver to trimethylamine-N-oxide (TMAO). Recent studies revealed that TMAO exacerbates atherosclerosis in mice and positively correlates with the severity of this disease in humans. However, which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., genotype) and diet affect TMA production and colonization of these microbes, and the effects TMA-producing microbes have on the bioavailability of dietary choline remain largely unknown. We screened a collection of 79 sequenced human intestinal isolates encompassing the major phyla found in the human gut and identified nine strains capable of producing TMA from choline in vitro. Gnotobiotic mouse studies showed that TMAO accumulates in the serum of animals colonized with TMA-producing species, but not in the serum of animals colonized with intestinal isolates that do not generate TMA from choline in vitro. Remarkably, low levels of colonization by TMA-producing bacteria significantly reduced choline levels available to the host. This effect was more pronounced as the abundance of TMA-producing bacteria increased. Our findings provide a framework for designing strategies aimed at changing the representation or activity of TMA-producing bacteria in the human gut and suggest that the TMA-producing status of the gut microbiota should be considered when making recommendations about choline intake requirements for humans.

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Author and article information

Journal

Journal ID (nlm-ta): Nutrients

Journal ID (iso-abbrev): Nutrients

Journal ID (publisher-id): nutrients

Title: Nutrients

Publisher: MDPI

ISSN (Electronic): 2072-6643

Publication date (Electronic): 07 August 2019

Publication date Collection: August 2019

Volume: 11

Issue: 8

Electronic Location Identifier: 1821

Affiliations

[1 ]Department of Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA

[2 ]Center for Inflammation, Translational and Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA

[3 ]Center for Metabolic Disease Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA

[4 ]Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey, Piscataway, NJ 08854, USA

Author notes

[* ]Correspondence: marion.chan@ 123456temple.edu ; Tel.: +1-(215)-707-8262

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Xiaofeng Yang https://orcid.org/0000-0002-6854-6195

Article

Publisher ID: nutrients-11-01821

DOI: 10.3390/nu11081821

PMC ID: 6723051

PubMed ID: 31394758

SO-VID: 65c8b5a0-64e4-46c3-9694-48b3177dc71c

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

The Microbial Metabolite Trimethylamine N-Oxide Links Vascular Dysfunctions and the Autoimmune Disease Rheumatoid Arthritis

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Karger: Nutrition and Dietetics

Most cited references 106

Formation of propionate and butyrate by the human colonic microbiota

Enterotypes in the landscape of gut microbial community composition

Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide

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