Short Chain Fatty Acids Due to Microbiota and Effect on Diseases

Yıl 2023, Cilt: 32 Sayı: 4, 246 - 253, 31.12.2023

Yusuf Döğüş , Amin Deami , Zafer Yönden

https://doi.org/10.17827/aktd.1330297

Öz

Short-chain fatty acids (SCFAs) are a subset of fatty acids produced by the gut microbiota during the fermentation of partially and indigestible polysaccharides. The highest levels of SCFA are found in the proximal colon, where they are used locally by enterocytes or transported into the bloodstream through the intestinal epithelium. Two main SCFA signaling mechanisms have been identified. These; the inhibition of histone deacetylases (HDAZs) and the activation of G-protein-coupled receptors (GPRs). Because HDAZs regulate gene expression, inhibition of HDAZs has a wide variety of down-regulated consequences. Our understanding of SCFA-mediated inhibition of HDAZs is still in its infancy. GPRs, particularly GPR43, GPR41, and GPR109A, have been identified as receptors for SCFAs. Studies have shown that these GPRs play an important role in the regulation of diseases and metabolism. They induce reactive oxygen species (ROS), alter cell proliferation and function, have anti-inflammatory, antitumorigenic, antimicrobial effects, and alter intestinal integrity. Recent research has found that SCFAs not only affect the signal transduction pathway in the gut but also reach tissues and organs outside the gut via their circulation in the blood. In this study; Given the broad effects of SCFAs and their levels being regulated by diet, we review the current understanding of their effects on host physiology with the aim of developing new therapeutic strategies for inflammatory diseases worldwide.

Anahtar Kelimeler

G-protein-coupled receptor, histone deacetylases, microbiota, short-chain fatty acids.

Mikrobiyota Kaynaklı Kısa Zincirli Yağ Asitleri ve Hastalıklar Üzerine Etkileri

Öz

Kısa zincirli yağ asitleri (KZYA'lar), kısmen ve sindirilemeyen polisakkaritlerin fermentasyonu sırasında bağırsak mikrobiyotası tarafından üretilen yağ asitlerinin bir alt kümesidir. En yüksek KZYA seviyeleri, enterositler tarafından lokal olarak kullanıldıkları veya bağırsak epiteli boyunca kan dolaşımına taşındıkları proksimal kolonda bulunur. İki ana KZYA sinyal mekanizması tanımlanmıştır. Bunlar; histon deasetilazların (HDAZ'lar) inhibisyonu ve G-protein-bağlı reseptörlerin (GPR'ler) aktivasyonudur. HDAZ'lar gen ekspresyonunu düzenlediğinden, HDAZ'ların inhibisyonunun çok çeşitli down regule sonuçları vardır. HDAZ'ların KZYA aracılı inhibisyonuna ilişkin anlayışımız henüz başlangıç aşamasındadır. GPR'ler, özellikle GPR43, GPR41 ve GPR109A, KZYA'lar için reseptörler olarak tanımlanmıştır. Çalışmalar, bu GPR'lerin hastalıkların ve metabolizmanın düzenlenmesinde önemli bir rol oynadığını göstermiştir. Bunlar reaktif oksijen türlerini (ROT) indüklemek, hücre çoğalmasını ve işlevini değiştirmek, anti-enflamatuar, antitümorijenik ve antimikrobiyal etkilere sahip ve bağırsak bütünlüğünü değiştirmektedir. Son zamanlarda yapılan araştırmalar, KZYA'ların yalnızca bağırsaktaki sinyal iletim yolunu etkilemekle kalmayıp, aynı zamanda kandaki dolaşımları yoluyla bağırsak dışındaki doku ve organlara da ulaştıkları bulmuştur. Bu çalışmada; KZYA'ların geniş etkileri ve seviyelerinin diyetle düzenlendiği göz önüne alındığında, dünyada enflamatuar hastalıklar için yeni terapötik strateji geliştirilmesi amaçlamak ve konak fizyolojisi üzerindeki etkilerine ilişkin mevcut anlayışı gözden geçmekteyiz.

Anahtar Kelimeler

g- protein bağlı reseptör, Histon deasetilazlar, Mikrobiyota, Kısa zincirli yağ asitleri

Destekleyen Kurum

yok

Kaynakça

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