Uloga crijevne mikrobiote u patogenezi neurodegenerativnih bolesti ljudi

master's thesis

• Title (english): The role of gut microbiota in the pathogenesis of neurodegenerative diseases in humans
• Author: Helena Vranić
• Mentor: Jasmina Vraneš (mentor)
• Committee member: Marko Banić (predsjednik povjerenstva)
• Committee member: Branka Bedenić (član povjerenstva)
• Committee member: Jasmina Vraneš (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Medical Microbiology and Parasitology); Zagreb
• Defense date and country: 2022-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Medical Microbiology

Abstract

Crijevna mikrobiota je kompleksna zajednica mikroorganizama smještena u specifičnom ekosustavu, čije izmjene imaju značajan utjecaj ne samo na različite poremećaje unutar tog ekosustava, već i na bolesti središnjeg živčanog sustava kao što su Alzheimerova i Parkinsonova bolest, amiotrofična lateralna skleroza, te druge neurodegenerativne bolesti. Dok je uloga crijevne mikrobiote u patogenezi gastrointestinalnih poremećaja kao što su ulcerozni kolitis i sindrom iritabilnog crijeva već dobro razjašnjena, njezina uloga u patogenezi neurodegenerativnih bolesti se tek posljednjih godina intenzivnije istražuje. Osovina mikrobiota crijeva–mozak je dvosmjerni komunikacijski sustav koji nije u potpunosti istražen, a obuhvaća različite neurološke, imunološke, endokrinološke i metaboličke signalne puteve. Istraživanja provedena na aksenički uzgojenim životinjama navode da crijevna mikrobiota ima značajnu ulogu u patogenezi neurodegenerativnih bolesti. Povećana propusnost crijeva i krvno-moždane barijere inducirana disbiozom može utjecati na patogenezu različitih neurodegenerativnih bolesti, posebice onih povezanih sa starenjem. Kratkolančane masne kiseline imaju značajnu ulogu u regulaciji mozga i ponašanja preko G-protein-vezanih receptora. Citokini koje stvaraju stanice imunološkog sustava u crijevima utječu na mozak preko hipotalamo-hipofizno-adrenalne osovine i otpuštanja kortizola. Terapijske opcije liječenja neurodegenerativnih bolesti koje bi utjecale na mikrobiom crijeva se istražuju i postoje dokazi da neke intervencije imaju povoljan učinak. Korištenje probiotika je dovelo do poboljšanja simptoma u bolesnika sa neurodegenerativnim bolestima, no postoje i kontradiktorni dokazi, te još nisu razvijene preporuke za kliničku primjenu.

Abstract (english)

The gut microbiota is a complex community of microorganisms located in a specific ecosystem, whose changes have a significant impact not only to various disturbances within that ecosystem, but also on diseases of central nervous system such as Alzheimer's disease and Parkinson's disease, amyotrophic lateral sclerosis and other neurodegenerative diseases. While the role of intestinal microbiota in the pathogenesis of gastrointestinal disorders such as ulcerative colitis and irritable bowel syndrome is already well understood, its role in the pathogenesis of neurodegenerative diseases has only been intensively investigated in recent years. The gut microbiota-brain axis is a two-way communication system that has not been fully explored, and includes various neurological, immunological, endocrinological and metabolic signaling pathways. Research on axenic animals indicates that the gut microbiota plays a significant role in the pathogenesis of neurodegenerative diseases. Dysbiosis-induced increased permeability of the gut and blood-brain barrier can affect the pathogenesis of various neurodegenerative diseases, especially those related to aging. Short-chain fatty acids play a significant role in the regulation of the brain and the behavior through G-protein-coupled receptors. Cytokines produced by cells of the immune system in the intestine affect the brain via the hypothalamic-pituitary-adrenal axis and the release of cortisol. Therapeutic options for the treatment of neurodegenerative diseases that would affect the gut microbiome are being investigated and there is evidence that some interventions have a benefical effect. The use of probiotics has led to improvement of symptoms in patients with neurodegenerative diseases, but there is also contradictory evidence, and recommendations for clinical use have not yet been developed.

• Keywords: crijevna mikrobiota; neurodegenerativne bolesti; upala; kratkolančane masne kiseline
• Keywords (english): gut microbiota; neurodegenerative disease; inflammation; short chain fatty acids
• Language: croatian
• URN:NBN: urn:nbn:hr:105:571867
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-03-22 12:32:45