Metabolome, genome and microbiome
The connection of the blood metabolome with the intestinal microbiota and the host genome will give the key to precision therapy
Alexander Biryuzov, PCR.news
Researchers from the Institute of Systems Biology (Seattle, USA) found out that the composition of metabolites in our blood is more influenced not by heredity, but by the intestinal microflora. The work is published in Nature Metabolism (Diener et al., Genome–microbiome interplay provides insight into the determinants of the human blood metabolome).
The composition of the blood, determined, among other things, by the products of metabolism, is an important diagnostic indicator. It is not by chance that a set of metabolite molecules (a metabolome) is figuratively called a molecular "mirror" of our health. Previous studies have established that the plasma metabolome is closely related to both genetics and the gut microbiome. In the new work, scientists decided to find out the degree of influence of each of these factors.
To this end, they collected and analyzed blood and stool samples. For blood, metabolites were determined using high-performance liquid chromatography with mass spectrometry and genome-wide sequencing (GWAS). Sequences of bacterial genes of 16S rRNA were determined in feces. All study participants were subscribers of the Arivale Scientific Wellness program, which involved deep phenotyping using multi-genome data combined with personalized training to improve overall health and well-being. (Arivale, the company that launched the program, has stopped its existence in 2019.) The selected cohort included 1,569 people, including 997 women and 572 men. The average age of the cohort was 49±11 years, the average BMI was 28.2±6.6.
The authors identified 930 blood metabolites and conducted a GWAS and a search for associations with the microbiome for each of them. Significant associations were established for 595 out of 930 molecules. At the same time, 69% of associations were due exclusively to the microbiome, 15% — exclusively to genetics and 16% were under hybrid control of the genome and microbiome. In particular, the latter included fatty acids, phenylalanine, tyrosine, pyrimidine and glycine.
The results of the study are considered promising because they provide clues to the development of therapy for metabolic disorders. They indicate that a large number of metabolites can be manipulated with the help of diet and probiotics. At the same time, metabolites under strict genetic control will not respond to lifestyle changes, and therefore they should be considered as targets for pharmacological interventions.
Unusual associations have been described for some metabolites. For example, ceramides were associated with the microbiome or with human genetic factors depending on the length of their chain. Ceramides have previously been shown to be involved in diseases such as Alzheimer's disease, depression and mood disorders. The separation of ceramides by their control factors will improve the design of precision therapeutic agents.
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