Projects / Programmes
The role of the microbiome in depression
| Code |
Science |
Field |
Subfield |
| 3.09.00 |
Medical sciences |
Psychiatry |
|
| Code |
Science |
Field |
| B650 |
Biomedical sciences |
Psychiatry, clinical psychology, psychosomatics |
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
microbiome, depression
Researchers (12)
Organisations (2)
Abstract
Major depressive disorder (MDD) presents a major health burden for individuals, families and the society. Lifetime risks vary from 10 to 25 % for women and 5 to 12 % for men. MDD is defined by episodes of low mood and/or anhedonia with changes in physical and psychological function. MDD is additionally associated with an increased risk of developing atherosclerosis, heart disease, hypertension, stroke, cognitive decline, and dementia, immune impairments and metabolic disorders including type 2 diabetes. Episodes of depression are highly recurrent; many adult cases of depression emerge in adolescence suggesting a stable and chronic lifelong course. MDD is regarded as a complex disorder in which both genetic and environmental factors contribute to the etiology. Nevertheless, the major part of genetic factors remains unrecognized so far (missing heritability). Psychiatric disorders are by role not associated with monogenic genetic predisposition, while genetic variability in so far identified genes/genomic regions explains only minor proportion of genetic contribution to the disease. Current “omic” studies predominantly exploited animal models and central nervous system tissue. It is vital to explore noninvasive approach to biomarker identification in human. In addition to blood which is accessible by minimally invasive procedures, saliva provides potential for disease biomarkers and can be obtained non-invasively. Evidence is accumulating that exposition to environmental factors (exposome), e.g. stressful stimuli in the early childhood (or even “in utero”and also later in life) could potentially contribute to lifelong predisposition to psychiatric disorders through epigenomic mechanisms. For example, it has been reported that child abuse can be associated with differences in methylation in various tissues, including saliva. Additionally, evidence indicates that the gut–brain axis provides a bidirectional homeostatic route of communication that uses neural, hormonal and immunological routes. Moreover, there is limited evidence that microbiome modifies epigenomic signatures as well. 1. Objective of the proposed research with particular emphasis on the originality of the proposed research and its potential impact for the development of new research directionsThe goal of the proposed research is to undertake first systems approach in terms of integrating various biological and environmental data to understand etiology and pathophysiology of MDD. For this purpose we plan to obtain new global scale experimental data of human epigenome (global methylation of the genome) in saliva in patients with MDD in comparison with controls. Additionally, salivary and gut microbiome data will be compared between MDD patients and non-depressive controls. These data are not available for MDD yet. In order to understand systemic/complex nature of MDD we will integrate epigenomic and microbiome data with data on exposome, concentrating on known epidemiological risk factors for MDD as well as with basic physiological data (blood glucose levels, blood pressure, BMI, psychological profiling). At genomic level we plan to analyze genetic variability in selected genes, so far consistently associated with MDD and/or stress disposition. The proposed research is developing Systems psychiatry as a new scientific field in medicine. We expect to obtain first global epigenomic and microbiome data in saliva which will give us the opportunity to asses the potential of these biomarkers for understanding etiology and pathogenesis of MDD. Systems approach integrating different levels of information (“omic”, exposome, psychological and physiological data) will provide new insights in the complex nature od MDD. Obtained data will contribute to improve diagnostics and consequently prevention and planing of public health interventions in MDD.
Significance for science
Mental diseases are as a rule not associated with monogenetic predisposition, i.e. mutations in individual genes, while the genetic variability in genes or genomes identified to date represents a minor portion of the assessed genetic component.
An important part of so-called “ome” studies was focused on animal models and detection of central nervous system lesions. For practical clinical use, the potential of other tissues and cells needs to be explored in the compartments which are accessible with noninvasive methods for identification of new biomarkers. In addition to the blood, which is accessible with minimally invasive approaches, the field of saliva biomarkers shows great promise, as saliva is accessible with a noninvasive approach, but this has been researched very little to date. Lately, research data has been collected that indicates the significance of environmental exposure (exposome), i.e. stress factors in early childhood (or even during pregnancy, as well as later in life), that could mark an individual for life via epigenomic mechanisms.
Current data on the role of the more recently found etiological and pathological factors in depression are fragmented and have been insufficiently validated. For better understanding of the causes of depression and the pathological mechanisms in the central nervous system as well as the comorbidity in depression, new research data is urgently needed, including various “ome” levels: genome, epigenome and microbiome, as well as a systemic approach to the integration of various levels of data, which in addition to “ome” levels also include physiological data and environmental factors (exposome) in the same subjects. Only in this way can one expect successful translation of research results into the clinical environment and preventative measures within the scope of public healthcare.
Significance for the country
Within the scope of the proposed project we will gain original new epigenomic and microbiomic data will be obtained from the saliva of subjects and that their significance in the etiology and pathogenesis of depression for the first time. Using a systemic approach to the integration of “ome” data and the physiological, psychological and exposome data an attempt will be made to evaluate the complex relationships of the studied parameters in the pathogenesis of depression. It is expected that the collected data will significantly contribute to the diagnosis and development of preventative measures for one of the presently most important diseases.
Most important scientific results
Interim report,
final report
Most important socioeconomically and culturally relevant results
Interim report,
final report
