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Projects / Programmes source: ARRS

Environmental and genetic factors in autism spectrum disorders

Research activity

Code Science Field Subfield
3.05.00  Medical sciences  Human reproduction   

Code Science Field
B000  Biomedical sciences   

Code Science Field
3.02  Medical and Health Sciences  Clinical medicine 
Keywords
Autism spectrum disorder, microbiota, biomarkers
Evaluation (rules)
source: COBISS
Researchers (17)
no. Code Name and surname Research area Role Period No. of publications
1.  19485  PhD Tomaž Accetto  Animal production  Researcher  2019 - 2022  156 
2.  08320  PhD Gorazd Avguštin  Animal production  Researcher  2019 - 2022  351 
3.  28292  MSc Elizabeta Božnar Alič  Cardiovascular system  Researcher  2019 - 2022  77 
4.  18299  PhD Urška Čegovnik Primožič  Biochemistry and molecular biology  Researcher  2019 - 2022  33 
5.  05098  PhD Peter Dovč  Biotechnology  Researcher  2019 - 2022  906 
6.  35405  Teja Fabjan  Medical sciences  Researcher  2019 - 2022  40 
7.  11765  PhD Lijana Fanedl  Animal production  Researcher  2019 - 2022  97 
8.  30074  Petra Finderle  Biochemistry and molecular biology  Researcher  2019 - 2022  29 
9.  27697  PhD Maja Jekovec Vrhovšek  Neurobiology  Researcher  2019 - 2022  90 
10.  34577  Kristina Kumer  Human reproduction  Researcher  2019 - 2022  55 
11.  37703  PhD Luka Lipoglavšek  Animal production  Researcher  2019 - 2022  49 
12.  36210  PhD Jerneja Maček  Psychiatry  Researcher  2019 - 2022  56 
13.  10691  PhD Joško Osredkar  Human reproduction  Principal Researcher  2019 - 2022  1,267 
14.  39091  Nika Rihar  Animal production  Junior researcher  2019 - 2022 
15.  35750  Vera Troha Poljančič    Technician  2019 - 2022 
16.  32581  PhD Minja Zorc  Computer science and informatics  Researcher  2019 - 2022  151 
17.  17864  PhD Maša Zorec  Animal production  Researcher  2019 - 2022  67 
Organisations (2)
no. Code Research organisation City Registration number No. of publications
1.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  72,474 
2.  0481  University of Ljubljana, Biotechnical Faculty  Ljubljana  1626914  63,757 
Abstract
Autistic spectrum disorder (ASD) or spectrum of autism disorders (SAD) is a developmental, multifactorial disorder characterized by symptoms that develop with age and have a negative impact on the development of the child. Over the past years, research has shown a dramatic increase in incidence of ASD. Although the direct cause of an increase in the prevalence of autism is unknown, the increase may be partly explained by increased awareness and improved diagnosis. Ethology and ASD's pathogenesis are not yet fully understood. Studies show that the heredity in ASD is an important factor, while a lesser emphasis is placed on defining the importance of various environmental factors. Autism can be derived from the interaction between genetic, environmental, behavioral and immunological factors, with oxidative stress as a mechanism that connects these risk factors. An increasing number of studies are studying the involvement of intestinal microbiota in ASD, especially in recent years with the methods of microbiomics. In different studies the reduced diversity of the entire microbiota and the changed proportions of some important microbial groups in ASD is described. One of the possible mechanisms contributing to inflammatory changes typical for ASD is increased intestinal permeability and consequent bacterial translocation or translocation of bacterial components, such as lipopolysaccharides (LPS) of cell walls of Gram negative bacteria, into systemic circulation. It is not yet well known whether children with ASD and GI symptoms are a unique phenotype within the ASD or if it is a co-morbidity that is not related to neurological development. We want to investigate whether microbiota and peripheral immune response in children with ASD symptoms will be altered and whether there are biological markers of immune dysfunction. For the assessment of the condition, we will determine the proinflammatory cytokines IL-1a, IL-1b, IL-6, IL-12 (p40 and p70) and the tumor necrosis factor (TNF) α. To evaluate the response of the T cells, we will analyze IFNDA (TH1), IL-4 and IL-13 (TH2), and to assess the immune regulation of IL-10 and the transforming growth factor (TGF) b1. In addition, also the levels of cytokines IL-5, IL-15 and IL-17 will be determined. Calprotectin is a calcium binding protein and is found in the cytoplasm of neutrophil granulocytes and macrophages. 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 directions, 1. Intestinal microbiome dysbiosis is characteristic and plays an important role in the development or presentation of ASD symptoms, which will be demonstrated by molecular microbiological analyzes involving amplicon deep sequencing of 16S rRNA genes and "shotgun" metagenomic sequencing of the microbial DNA isolated from the samples of the selected patients 2. In children with ASD, we expect increased concentrations of inflammatory factors 3. In children with ASD, we expect increased isopropanol concentrations and the changed ratios of the short-chain fatty acids and bile acids in faeces, which will be in correlation with the changes in the microbiome, as a consequence of the increased / decreased number of genes involved in the metabolism of these substances 4. In children with ASD, a change in the ratio of quinurenine / tryptophan to urine is expected 5. In children with ASD, higher concentrations of calprotectin in faeces are expected 6. On the basis of the analysis of exome sequences of the selected subgroup of the study participants, using the machine learning methodology, we will try to disclose the connections between the genomic data and the data retrieved from the analysis of the microbiome, immune status and metabolic markers
Significance for science
With the proposed study, we want to see which potential biochemical markers are in those patients with ASD, where the parameters (metals, porphyrins, inflammatory factors) remain within the limits of normal values. Because more than half of children with ASD have sleep disorders, we can get an insight into the mechanism of insomnia by analyzing these parameters. We will partly focus on the analysis of parameters in the urine, and in this way we also try to determine how representative of the insomnia would be the urine sample for analysis in children, where we avoid blood collection. The University Clinical Center, as a leading institution, and for this reason must ensure the implementation of the development and implementation of new knowledge in the fields of national pathology and prevention, and contribute to the development of policies for the country. In the previous projects, we have set up methods for determining the parameters of oxidative stress that have not yet been introduced in Slovenia, and this is an important contribution to diagnostics. With the proposed project, however, we want to extend the range of investigations to the parameters related to sleep disorders. However, since it is known that microbiota is important for patients with ASD and other developmental neurological disorders, we will start sampling of stool within this project. Since children from all over Slovenia are treated at the Centre for Autism, the results of this study will be the basis for the guidelines for the treatment of children with ASD and other development of neurological disorders.
Significance for Slovenia
With the proposed study, we want to see which potential biochemical markers are in those patients with ASD, where the parameters (metals, porphyrins, inflammatory factors) remain within the limits of normal values. Because more than half of children with ASD have sleep disorders, we can get an insight into the mechanism of insomnia by analyzing these parameters. We will partly focus on the analysis of parameters in the urine, and in this way we also try to determine how representative of the insomnia would be the urine sample for analysis in children, where we avoid blood collection. The University Clinical Center, as a leading institution, and for this reason must ensure the implementation of the development and implementation of new knowledge in the fields of national pathology and prevention, and contribute to the development of policies for the country. In the previous projects, we have set up methods for determining the parameters of oxidative stress that have not yet been introduced in Slovenia, and this is an important contribution to diagnostics. With the proposed project, however, we want to extend the range of investigations to the parameters related to sleep disorders. However, since it is known that microbiota is important for patients with ASD and other developmental neurological disorders, we will start sampling of stool within this project. Since children from all over Slovenia are treated at the Centre for Autism, the results of this study will be the basis for the guidelines for the treatment of children with ASD and other development of neurological disorders.
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