The Short Chain Free Fatty Acids and Their Receptors in the Microbiotic Concept for Asthma Development

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Abstract

Asthma is a chronic, heterogeneous inflammatory disease with a high variability of the flow caused by the trigger influence of genetic and environmental factors. The heterogeneity of asthma indicates the involvement of many components in the mechanism of the inflammation of the respiratory tract. Currently, the microbiotic concept of the pathogenesis of respiratory system diseases is studied, based on the existence of a bilateral relationship between the microflora lungs and the intestines. The key mechanism of these relationships is free fatty acids performing signal and regulatory functions in the body. The medium-chain and long-chain free fatty acids are synthesized by de novo or enter the body as a result of consumption of fats, while the short-chain free fatty acids are formed in the intestine as a result of partial digestion of soluble fibre. The mechanism connecting the free fatty acids and inflammatory reactions includes activation of their receptors (Free Fatty Acid Receptor, FFAR) expressed on the cells of the gastrointestinal and respiratory tract, as well as on immune cells. If the role of the medium-chain and long-chain fatty acids receptors (FFAR1, FFAR4) and their ligands in the pathogenesis of asthma is actively studied, the value of the short-chain receptors (FFAR2, FFAR3) only begins to attract the attention of researchers in connection with the emergence of numerous data on the interconnection of the respiratory microbiome paths and intestines and its possible role in the induction of broncho-pulmonary complications. This review includes modern knowledge of the microbiotic concept of asthma, the basic information about the nomenclature, metabolism and transport of the free fatty acids, the value of the individual classes of the free fatty acids in the regulation of immune processes is normal and at bronchopulmonary pathology. The latest data of the FFAR receptors are systematized, features of their activation and expression, the intended role of FFAR2 and FFAR3 in the development and asthma therapy. It is discussed that gastrointestinal microbiota correction can reduce the activity of chronic inflammation of the respiratory tract at asthma.

About the authors

Oksana Y. Kytikova

Far Eastern Scientific Center of Physiology and Pathology of Respiration

Email: kytikova@yandex.ru
ORCID iD: 0000-0001-5018-0271
SPIN-code: 3006-5614

MD, PhD

Russian Federation, 22 Kalinina str., 675000, Blagoveschensk

Yuliya K. Denisenko

Far Eastern Scientific Center of Physiology and Pathology of Respiration

Email: karaman@inbox.ru
ORCID iD: 0000-0003-4130-8899
SPIN-code: 4997-3432

PhD in Biology

Russian Federation, 22 Kalinina str., 675000, Blagoveschensk

Tatyana P. Novgorodtseva

Far Eastern Scientific Center of Physiology and Pathology of Respiration

Email: nauka@niivl.ru
ORCID iD: 0000-0002-6058-201X
SPIN-code: 5888-6099

PhD in Biology, Professor

Russian Federation, 22 Kalinina str., 675000, Blagoveschensk

Marina V. Antonyuk

Far Eastern Scientific Center of Physiology and Pathology of Respiration

Email: antonyukm@mail.ru
ORCID iD: 0000-0002-2492-3198
SPIN-code: 3446-4852

MD, PhD, Professor

Russian Federation, 22 Kalinina str., 675000, Blagoveschensk

Tatyana A. Gvozdenko

Far Eastern Scientific Center of Physiology and Pathology of Respiration

Author for correspondence.
Email: vfdnz@mail.ru
ORCID iD: 0000-0002-6413-9840
SPIN-code: 7869-1692

MD, PhD, Professor

Russian Federation, 22 Kalinina str., 675000, Blagoveschensk

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2. Fig. 1. The mechanism of FFAR1 influence on the contraction of smooth muscles of the respiratory tract. Short- and medium-chain LCCs bind to FAR 1 and activate the receptor. The Gßy subunit dissociated from FFAR1 activates the membrane phospholipase Cß (PLCß), which, in turn, hydrolyzes phosphatidylinositol-4,5-bisphosphonate (PIP2) into diacylglycerin (DAG) and inositol triphosphate (IP3).IP3, binding to the IP3 receptor located on the sarcoplasmic reticulum, leads to the outflow of Ca2 + in cytoplasm, which causes the contraction of the smooth muscles of the respiratory tract

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