GENETIC VARIANTS, METABOLOME, AND GUT MICROBIOME BIOMARKERS FOR OBESITY AND AGING IN RANDOMLY SELECTED KAZAKH INDIVIDUALS
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Date
2020
Authors
Akilzhanova, Ainur
Rakhimova, Saule
Kozhamkulov, Ulan
Kairov, Ulykbek
Kushugulova, Almagul R.
Terwilliger, Joseph
Lee, Joseph
Journal Title
Journal ISSN
Volume Title
Publisher
International conference "MODERN PERSPECTIVES FOR BIOMEDICAL SCIENCES: FROM BENCH TO BEDSIDE”; National Laboratory Astana
Abstract
Objective: Metabolic syndrome (MS) is a cluster of inter-related and heritable metabolic traits, which
collectively impart unsurpassed risk for atherosclerotic cardiovascular disease and type 2diabetes. Considerable
work has been done to understand the underlying disease mechanisms by elucidating its genetic
etiology. Genome, Metabolome variations and gut microbiome can predict disease risk and diagnosis
and help to understand molecular pathophysiology. We aimed toassess plasma metabolom differences
and gut microbiome as well as genetic variants among Kazakh population to identify and characterize the
genetic, metabolic profiles and host-gut microbiota interactions.
Methods: Kazakhs were recruited into study after signing of informed consent in Astana, Kazakhstan.
Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS) (Metabolon,
USA) and NGS16S rRNA gene-sequence-based methods were used. Bioinformatic and statistical analyses
were performed.
Results: Subjects were stratified by age (young <45y, old ≥45y), gender and BMI. 853 different biochemical
indicators of the main pathways for the metabolism were identified in plasma. Results demonstrate
alterations in various metabolic pathways in older participants compared to younger subjects. Metabolic
differences included changes in metabolites associated with the metabolism of fatty acids, steroidogenesis,
secondary carnitine metabolism, inflammation and oxidative stress. Microbiomes of older persons
are characterized by a high level of microorganisms involved in the processing of plant substrates, butyrate-
producing bacteria and also has higher values of opportunistic microorganisms, representatives
of the Tenericutes family. The biodiversity index of the microbiome of older persons is reduced in comparison
with the biodiversity index in younger participants. This may indicate the influence on the microbiome
characteristics of such factors as genotype, nutrition, lifestyle.Genetic risk factors associated with
the obesity and hypertension were identified.
Conclusions: Understanding plasma metabolome and gut microbiome is essential to the development
of future personalized strategies of healthcare. Genome-wide association studies (GWAS) have been
widely utilized albeit with modest success in identifying variants that are associated with more than two
metabolic traits. Further studies with detailed analysis are needed to clarify host-gut genetic and metbolome
interactions.
Study was supported by a grant from the Ministry Education and Science, Republic of Kazakhstan
(BR05236508).
Description
Keywords
genetics, metabolome,, microbiome, metabolic syndrome, obesity, aging, Research Subject Categories::MEDICINE