Kardiyovasküler Hastalıklarda Bağırsak Mikrobiyota Metaboliti Trimetilamin N-oksit (TMAO) : Önleme ve Tedavi İçin Yeni Bir Molekül mü?

Öz

Dünya çapında ölümlerin en önde gelen nedeni olan kardiyovasküler hastalıkların önlenmesi ve prognozunun kontrolünde bağırsak mikrobiyota türevli moleküllerin katkısının bulunması ile bağırsak ve kardiyovasküler sistem arasındaki bağlantıya olan ilgi önemli ölçüde artmıştır. Güncel çalışmalar bağırsak mikrobiyomu ve metabolitlerinin ateroskleroz, hipertansiyon, kalp yetmezliği, atrial fibrilasyon ve miyokard fibrozu gibi kardiyovasküler hastalıkların başlangıcında ve ilerlemesinde önemli rol oynadığını göstermektedir. Diyetin içeriği bağırsak mikrobiyotasını değiştiren önemli bir faktördür. Hayvansal kaynaklarda bulunan kolin ve L-karnitinin bağırsak mikroorganizmaları tarafından metabolize edilmesiyle trimetilamin (TMA) oluşmaktadır. Üretilen TMA?nın çoğunluğu pasif olarak portal dolaşıma geçmekte ve hepatik flavine bağımlı monooksigenazlar (FMO?lar) tarafından trimetilamin-N-oksit (TMAO)?e okside edilmektedir. Kırmızı et, süt ürünleri, yumurta, balık ve kümes hayvanlarında bol miktarda bulunan fosfotidilkolin, L-karnitin ve betain TMA kaynağı olan bileşiklerdir. Trimetilamin veya öncüllerini içeren besinler kan ve idrar TMAO düzeylerini artırmaktadır. Son zamanlarda birçok çalışmada TMAO düzeylerinin yüksek olması kardiyovasküler hastalık riski ile ilişkilendirilmektedir. Kardiyovasküler hastalıklar ve TMAO arasındaki bağlantının anlaşılması; TMAO?nun bir biyomarker olup olmadığının belirlenmesi ve TMAO?yu etkileyen diyet bileşenlerinin varlığının tespit edilmesi yeni tedavi yaklaşımlarına odaklanılması açısından önemlidir. Böylece, bu derleme kırmızı et ve diğer hayvansal ürünlerde bulunan kolin ve L-karnitinin bir metaboliti olan TMAO?nun kardiyovasküler hastalıklar üzerine etkisini içeren mekanizmalar ile ilgili literatürün derlenmesi amacıyla yazılmıştır.

Anahtar Kelimeler

• Diyet
• Beslenme
• Mikrobiyota
• TMAO
• Ateroskleroz

Gut Microbiota-Dependent Metabolite Trimethylamine N-oxide (TMAO), in Cardiovascular Diseases: A New Molecule for Prevention and Treatment?

Abstract

ABSTRACT There has been an increasing interest in the relationship between the gut and the cardiovascular system, since the contribution of intestinal microbiota-derived molecules in the prevention and control of the prognosis of cardiovascular diseases, the leading cause of mortality worldwide, was determined. Current studies have demonstrated that intestinal microbiome and its metabolites play a significant role in the development and progression of cardiovascular diseases such as atherosclerosis, hypertension, heart failure, atrial fibrillation and myocardial fibrosis. The content of the diet is an important factor that changes the gut microbiota. Trimethylamine (TMA) is produced by the intestinal microorganisms which metabolize choline and L-carnitine found in animal sources. The majority of the TMA produced passively passes into the portal circulation and is oxidized to trimethylamine-N-oxide (TMAO) by the hepatic flavin-dependent monooxygenases (FMOs). Phosphatidylcholine, L-carnitine and betaine which are abundant in red meat, dairy products, eggs, fish and poultry are the sources of TMA. Foods containing trimethylamine or its precursors increase TMAO levels in blood and urine. In many studies conducted recently, high levels of TMAO have been associated with the risk of cardiovascular diseases. Understanding the relationship between cardiovascular diseases and TMAO, determining whether TMAO is a biomarker and determining the presence of dietary components affecting TMAO are of importance in focusing on new treatment approaches. Thus, this review was performed to compile the literature on the mechanisms involving the effect of TMAO, a metabolite of choline and L-carnitine found in red meat and other animal products, on cardiovascular diseases.

Keywords

• Diet
• Nutrition
• Microbiota
• TMAO
• Atherosclerosis

Kaynakça

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