THE INFLUENCE OF MODULATION OF INTESTINAL MICROBIOTA ON CLINICAL AND IMMUNOLOGICAL PARAMETERS AND OXYTOCIN LEVELS IN CHILDREN WITH AUTISM SPECTRUM DISORDERS
- Authors: Cherevko N.A.1, Novikov P.S.2, Arkhipov A.M.2, Loginova E.A.1, Khudyakova M.I.1, Vekovtsev A.A.3, Bylin P.G.3
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Affiliations:
- Federal State Budgetary Educational Institution of Higher Education "Siberian State Medical University" of the Ministry of Health of the Russian Federation, 634055, Moskovsky tract, 2, Tomsk, Russia
- Center for Family Medicine, 634009, st. Voikova, 55, Tomsk, Russia
- Scientific and Production Association "ArtLife"", 634034, Nakhimova str., 8/2, Tomsk region, Tomsk city, Russia
- Section: Joint Immunology Forum 2024
- URL: https://rusimmun.ru/jour/article/view/16873
- DOI: https://doi.org/10.46235/1028-7221-16873-TIO
- ID: 16873
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Abstract
Abstract
Autism spectrum disorders are associated with an imbalance of immune and neurological disorders, starting after the age of two. The study is devoted to studying the role of specialized strains of bacteria Lactobacillus reuteri, which mediate the synthesis of oxytocin in humans and influence inflammation indicators.Bacteria of this strain were part of the biologically active additive “Panbiolact Mental”, developed and presented by NPO ArtLife (Tomsk). The purpose of the work was to assess the effect of specialized strains of bacteria Lactobacillus reuteri on changes in the composition of the intestinal microbiota, oxytocin levels, and immune parameters of children with ASD. The study included 43 children with autism spectrum disorders who took Panbiolact Mental for 90 days. The study materials included venous blood samples and fecal samples. The concentrations of cytokines (interleukins -4, -10, tumor necrosis factor alpha, interferon gamma), immunoglobulins (IgE, IgG, IgA, IgM) and the neuropeptide oxytocin were determined in the blood serum. Fecal samples were used to assess the qualitative and quantitative composition of the colon microbiota. Clinical symptoms of the disease associated with quality of life were assessed using the standard ATEC test scale (Autism Treatment Evaluation Checklist), expressed in scores corresponding to the severity of clinical and neurological parameters of the disease. In children with autism spectrum disorders, after 90 days of regular use of Panbiolact Mental, the number of bacteria of the genera Acinetobacter decreased, the number of Bacteroides species pluralis, Akkermansia muciniphila, Eubacterium rectale, Prevotella species pluralis and Methanobrevibacter smithii increased. Increases in the concentration of oxytocin, the protolerogenic coefficient IL-10/TNFα, immunoglobulins M and G, and a decrease in the concentrations of TNFα and IL-10 were recorded. The results of the study support the hypothesis of a significant role of gut microbiota diversity in the neuro-immune pathogenesis of autism spectrum disorders. "Panbiolact Mental" is presented as a potentially effective remedy for an integrated approach to the correction of ASD in children. These data may form the basis for further research in the field of probiotic therapy, as well as for the development of new strategies based on modulation of the intestinal microbiota.
About the authors
Natalia Anatolievna Cherevko
Federal State Budgetary Educational Institution of Higher Education "Siberian State Medical University" of the Ministry of Health of the Russian Federation, 634055, Moskovsky tract, 2, Tomsk, Russia
Email: chna@0370.ru
ORCID iD: 0000-0003-1023-4137
SPIN-code: 7291-1102
DSc (Medicine), MD, Immunology&Allergy Dept Professor, Siberian State Medical University
Russian Federation, 634055, Moskovsky tract, 2, Tomsk, Russia; 634009, st. Voikova, 55, Tomsk, Russia;Pavel Sergeevich Novikov
Center for Family Medicine, 634009, st. Voikova, 55, Tomsk, Russia
Email: pavel.n1234@yandex.ru
PhD applicant, Department of Pathophysiology, Siberian State Medical University, MD, Head of the Clinical Diagnostic Laboratory of the Medical Association “Center for Family Medicine”
Russian Federation, 634009, st. Voikova, 55, Tomsk, Russia;634055, Moskovsky tract, 2, Tomsk, Russia;Alexander Mikhailovich Arkhipov
Center for Family Medicine, 634009, st. Voikova, 55, Tomsk, Russia
Email: aram@0370.ru
clinical laboratory diagnostics doctor at the Family Medicine Center medical association
Russian Federation, 634009, st. Voikova, 55, Tomsk, RussiaElizaveta Aleksandrovna Loginova
Federal State Budgetary Educational Institution of Higher Education "Siberian State Medical University" of the Ministry of Health of the Russian Federation, 634055, Moskovsky tract, 2, Tomsk, Russia
Email: loginova.elizavetka@bk.ru
5th year student of the Faculty of Medicine, Siberian State Medical University
Russian Federation, 634055, Moskovsky tract, 2, Tomsk, RussiaMaria Ivanovna Khudyakova
Federal State Budgetary Educational Institution of Higher Education "Siberian State Medical University" of the Ministry of Health of the Russian Federation, 634055, Moskovsky tract, 2, Tomsk, Russia
Email: khudiakovami@mail.ru
ORCID iD: 0000-0002-6320-5017
Applicant for the Department of Pathophysiology, Siberian State Medical University
Russian Federation, 634055, Moskovsky tract, 2, Tomsk, RussiaAndrey Alekseevich Vekovtsev
Scientific and Production Association "ArtLife"", 634034, Nakhimova str., 8/2, Tomsk region, Tomsk city, Russia
Email: andrey@artlife.ru
Candidate of Medical Sciences, Director for Science and Production Scientific and Production Association, ArtLife LLC
Russian Federation, 634034, Nakhimova str., 8/2, Tomsk region, Tomsk city, RussiaPavel Gennadievich Bylin
Scientific and Production Association "ArtLife"", 634034, Nakhimova str., 8/2, Tomsk region, Tomsk city, Russia
Author for correspondence.
Email: bpg@artlife.ru
Leading engineer for the implementation of new equipment and technologies Production Scientific and Production Association, ArtLife LLC
Russian Federation, 634034, Nakhimova str., 8/2, Tomsk region, Tomsk city, RussiaReferences
- Coretti L., Paparo L., Riccio M.P., Amato F., Cuomo M., Natale A., Borrelli L., Corrado G., De Caro C., Comegna M., Buommino E., Castaldo G., Bravaccio C., Chiariotti L., Canani R.B., Lembo F. Gut Microbiota Features in Young Children With Autism Spectrum Disorders. Front Microbiol., 2018, Vol. 9, pp. 1-9. doi: 10.3389/fmicb.2018.03146
- Dinan T.G., Cryan J.F. Gut-brain axis in 2016: Brain-gut-microbiota axis - mood, metabolism and behaviour. Nat Rev Gastroenterol Hepatol, 2017, Vol. 14, no. 2, pp. 69-70. doi: 10.1038/nrgastro.2016.200
- Dinan T.G., Stilling R.M., Stanton C., Cryan J.F. Collective unconscious: how gut microbes shape human behavior. J. Psychiatr. Res., 2015, Vol. 63, pp. 1-9. doi: 10.1016/j.jpsychires.2015.02.021
- Erdman S.E. Oxytocin and the microbiome. Curr. Opin. Endocr. Metab. Res., 2021, Vol. 19, August, pp. 8-14. doi: 10.1016/j.cpnec.2023.100205
- Flint H..J., Scott K.P., Louis P., Duncan S.H. The role of the gut microbiota in nutrition and health. Nature Reviews Gastroenterology & Hepatology, 2012, Vol. 9(10) pp. 577-589. doi: 10.1038/nrgastro.2012.156
- Foster J.A., Rinaman L., Cryan J.F. Stress & the gut-brain axis: Regulation by the microbiome. Neuron., 2017, Vol. 7, pp. 124-136. doi: 10.1016/j.ynstr.2017.03.001
- Huang M., Liu K., Wei Z., Feng Z., Chen J., Yang J., Zhong Q., Wan G., Kong X.J. Serum Oxytocin Level Correlates With Gut Microbiome Dysbiosis in Children With Autism Spectrum Disorder. J. Neurosci., 2021, Vol. 15, pp. 81-90 doi: 10.3389/fnins.2021.721884
- Kaisar M.M.., Pelgrom L.R., van der Ham A.J., Yazdanbakhsh M., Everts B. Butyrate Conditions Human Dendritic Cells to Prime Type 1 Regulatory T Cells via both Histone Deacetylase Inhibition and G Protein-Coupled Receptor 109A Signaling. Front. Immunol., 2017, Vol. 8, pp 1-12 doi: 10.3389/fimmu.2017.01429
- Kong X., Probiotic and Oxytocin Combination Therapy in Patients with Autism Spectrum Disorder: A Randomized, Double-Blinded, Placebo-Controlled Pilot Trial. Nutrients., 2021, Vol. 13, no. 5., pp 1552-1569. doi: 10.3390/nu13051552
- Lombardi V.C., De Meirleir K.L., Subramanian K., Nourani S.M., Dagda R.K., Delaney S.L., Palotás A. Nutritional Modulation of the Intestinal Microbiota; Future Opportunities for the Prevention and Treatment of Neuroimmune and Neuroinflammatory Disease. J Nutr Biochem, 2018, Vol. 61, pp. 1-16. doi: 10.1016/j.jnutbio.2018.04.004
- Luna R.A., Oezguen N., Balderas M., Anderson G.M., Savidge T., Williams K.C. Distinct Microbiome-Neuroimmune Signatures Correlate With Functional Abdominal Pain in Children With Autism Spectrum Disorder. Cellular and Molecular Gastroenterology and Hepatology, 2017, Vol. 3, pp. 218-230. doi: 10.1016/j.jcmgh.2016.11.008
- Ma B., Liang J., Dai M., Wang J., Luo J., Zhang Z., Jing J. Altered gut microbiota in Chinese children with autism spectrum disorders. Frontiers in Cellular and Infection Microbiology, 2019, Vol. 9., pp. 400-410 doi: 10.3389/fcimb.2019.00040
- Mangiola F., Ianiro G., Franceschi F., Fagiuoli S., Gasbarrini G., Gasbarrini A. Gut microbiota in autism and mood disorders. World Journal of Gastroenterology, 2016, Vol. 22, no. 1, pp. 361–368. doi: 10.3748/wjg.v22.i1.361
- Pulikkan J., Maji A., Dhakan D.B., Saxena R., Mohan B., Anto M.M., Agarwal N., Grace T., Sharma V.K. Gut Microbial Dysbiosis in Indian Children with Autism Spectrum Disorders. Microbial Ecology, 2018, Vol. 76, no. 4, pp. 1102-1114.
- doi: 10.1007/s00248-018-1176-2
- Rinninella E., Raoul P., Cintoni M., Franceschi F., Miggiano G.A.D., Gasbarrini A., Mele M.C. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms, 2019, Vol. 7, no. 1., pp. 14-36 doi: 10.3390/microorganisms7010014