The role of bacterial metabolites derived from aromatic amino acids in non-alcoholic fatty liver disease

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Abstract

The review deals with the role of aromatic amino acids and their microbial metabolites in the development and progression of non-alcoholic fatty liver disease (NAFLD). Pathological changes typical for NAFLD, as well as abnormal composition and/or functional activity of gut microbiota, results in abnormal aromatic amino acid metabolism. The authors discuss the potential of these amino acids and their bacterial metabolites to produce both negative and positive impact on the main steps of NAFLD pathophysiology, such as lipogenesis and inflammation, as well as on the liver functions through regulation of the intestinal barrier and microbiota-gut-liver axis signaling. The review gives detailed description of the mechanism of biological activity of tryptophan and its derivatives (indole, tryptamine, indole-lactic, indole-propyonic, indole-acetic acids, and indole-3-aldehyde) through the activation of aryl hydrocarbon receptor (AhR), preventing the development of liver steatosis. Bacteria-produced phenyl-alanine metabolites could promote liver steatosis (phenyl acetic and phenyl lactic acids) or, on the contrary, could reduce liver inflammation and increase insulin sensitivity (phenyl propionic acid). Tyramine, para-cumarate, 4-hydroxyphenylacetic acids, being by-products of bacterial catabolism of tyrosine, can prevent NAFLD, whereas para-cresol and phenol accelerate the progression of NAFLD by damaging the barrier properties of intestinal epithelium. Abnormalities in bacterial catabolism of tyrosine, leading to its excess, stimulate fatty acid synthesis and promote lipid infiltration of the liver. The authors emphasize a close interplay between bacterial metabolism of aromatic amino acids by gut microbiota and the functioning of the human body. They hypothesize that microbial metabolites of aromatic amino acids may represent not only therapeutic targets or non-invasive biomarkers, but also serve as bioactive agents for NAFLD treatment and prevention.

About the authors

E. S. Shcherbakova

State Research Institute of Especially Purified Bioproducts

Author for correspondence.
Email: elenka.shcherbakova@ya.ru
ORCID iD: 0000-0002-4268-8881

Elena S. Shcherbakova – Junior Research Fellow, Laboratory of Microbiology

7 Pudozhskaya ul., Saint Petersburg, 197110

Russian Federation

T. S. Sall

State Research Institute of Especially Purified Bioproducts

Email: miss_taty@mail.ru
ORCID iD: 0000-0002-5890-5641

Tatyana S. Sall – Junior Research Fellow, Laboratory of Microbiology

7 Pudozhskaya ul., Saint Petersburg, 197110

Russian Federation

S. I. Sitkin

State Research Institute of Especially Purified Bioproducts;
North Western State Medical University named after I.I. Mechnikov

Email: drsitkin@gmail.com
ORCID iD: 0000-0003-0331-0963

Stanislav I. Sitkin – MD, PhD, Leading Research Fellow, Laboratory of Microbiology State Research Institute of Especially Purified Bioproducts ; Associate Professor, Chair of Internal Medicine, Gastroenterology and Dietetics n.a. S.M. Ryss North Western State Medical University named after I.I. Mechnikov

7 Pudozhskaya ul., Saint Petersburg, 197110,

47 Piskarevskiy prospekt, Saint Petersburg, 195067

Russian Federation

T. Ya. Vakhitov

State Research Institute of Especially Purified Bioproducts

Email: tim-vakhitov@yandex.ru
ORCID iD: 0000-0001-8221-6910

Timur Ya. Vakhitov – PhD (in Biol.), Chief Research Fellow, Laboratory of Microbiology

7 Pudozhskaya ul., Saint Petersburg, 197110

Russian Federation

E. V. Demyanova

State Research Institute of Especially Purified Bioproducts

Email: lenna_22@mail.ru
ORCID iD: 0000-0002-1872-3464

Elena V. Demyanova – PhD (in Pharmacy), Head of Laboratory of Microbiology

7 Pudozhskaya ul., Saint Petersburg, 197110

Russian Federation

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