The importance of microbiome in human health
Kuupäev
2022-09-26
Autorid
Ajakirja pealkiri
Ajakirja ISSN
Köite pealkiri
Kirjastaja
Abstrakt
Tehnoloogia areng on andnud inimesele võimaluse uurida ümbritsevat maailma nurkade alt, mille jaoks veel mõned kümnendid tagasi võimalused puudusid. Üks selliseid teadusvaldkondi on inimese mikrobioomi ehk meie kehal ja kehas elavate mikroorganismide nagu näiteks bakterite ja viiruste uurimine. On teada, et mikrobioomil on oluline funktsioon inimese tervisele ning mikrobioomi kooslust omakorda mõjutavad suurel määral meie elustiil, toitumisharjumused, ümbritsev keskkond ning tervislik seisund. Just seosed haigustega on tekitanud huvi mikrobioomi kasutamiseks meditsiinilistes rakendustes. Doktoritöö eesmärk oli uurida, millised faktorid lisaks teadaolevatele on seotud meie soolestiku mikrobioomi kooslusega ning kuidas on mikrobioomi andmeid võimalik kasutada haiguste diagnoosimiseks ning haigusriskide hindamiseks. Esiteks uurisime teist tüüpi diabeeti ning näitasime, et mikrobioom aitab senisest täpsemalt ennustada muutusi veresuhkru regulatsiooni kirjeldavates parameetrites, milleks olid eelkõige insuliini eritamisega seotud näitajaid. Järgmiseks eesmärgiks oli kirjeldada Eesti populatsiooni soolestiku mikrorbioomi profiiili ning tuvasatada mikrobioomi kooslust mõjutavad faktorid. Eesti Geenivaramu terviseandmestikku kasutades tuvastasime, et antibiootikumide pikaajalisel korduval kasutamisel on akkumuleeruv mõju mikrobioomi kooslusele olenemata sellest, kas antibiootikume on kasutatud viimase kuue kuu jooksul. Analüüsides pikaajalise antibiootikumide mõju arvesse võtmine võimaldas omakorda täpsustada haigusspetsiifilisi muutusi mikrobioomis. Lisaks uurisime, kas soolestiku mikrobioomi abil inimeste grupeerimine võimaldaks ka kasutust kliinilistes rakendustes. Selgus, et selliselt mikrobioomi kooslust lihtsustades on võimalik küll anda hinnang inimese üldisele elustiilile, kuid tõendid haiguste diagnoosimisel või haiguste riski hindamiseks pole piisavalt tugevad. Kokkuvõttes on mikrobioomi uurimisel meditsiinis suur potentsiaal, mis võimaldab täiendada olemasolevaid võimalusi haiguste diagnoosimiseks ning riskide hindamiseks, kuid see eeldab täiendavaid teadmisi ja uuringuid.
The technological revolution allows us to study the world beyond the limits that were holding us back only a couple of decades ago. One of such fields is the study of the human microbiome. Tiny microorganisms making up the microbiome such as bacteria and viruses have been known to intervene with our health for centuries, but the whole microbial ecosystem has turned out to be more complex than previously thought. The extent of the role of the microbiome to our own functioning and well-being is just starting to unravel. Nevertheless, microbiome has been associated with a large variety of intrinsic and extrinsic factors, including various complex diseases. This evidence is leading a slow but steady progress towards clinical applications such as using microbiome for improving disease diagnostics or estimating the risk of developing a condition. This thesis aimed to expand the understanding of the factors influencing our gut microbiome composition and assess the possibility and challenges in using the microbiome composition for the clinical applications. Firstly, we identified novel microbial biomarkers for identifying the progression of type 2 diabetes (T2D), which can be used to improve the current risk estimation. Secondly, using the comprehensive health data available in the Estonian Biobank, we characterized the profile of the gut microbiome in the Estonian population and identified various factors affecting the microbiome. Our study indicated that the long-term antibiotics usage has an accumulative effect on the gut microbiome composition independent of recent usage. The novelty of this result has a significant impact on the microbiome field and the future analysis need to account for such drug effects. Lastly, we considered dividing the subjects into a few distinct clusters based on their microbiome composition and evaluated the clinical applicability of such representation. We showed that although this approach is desirable in its simplicity, it is not sufficient for clinical applications. In conclusion, the microbiome science is heading towards clinical applications, but exploratory analysis is still needed. Nevertheless, the challenges ahead do not overshadow the enthusiasm.
The technological revolution allows us to study the world beyond the limits that were holding us back only a couple of decades ago. One of such fields is the study of the human microbiome. Tiny microorganisms making up the microbiome such as bacteria and viruses have been known to intervene with our health for centuries, but the whole microbial ecosystem has turned out to be more complex than previously thought. The extent of the role of the microbiome to our own functioning and well-being is just starting to unravel. Nevertheless, microbiome has been associated with a large variety of intrinsic and extrinsic factors, including various complex diseases. This evidence is leading a slow but steady progress towards clinical applications such as using microbiome for improving disease diagnostics or estimating the risk of developing a condition. This thesis aimed to expand the understanding of the factors influencing our gut microbiome composition and assess the possibility and challenges in using the microbiome composition for the clinical applications. Firstly, we identified novel microbial biomarkers for identifying the progression of type 2 diabetes (T2D), which can be used to improve the current risk estimation. Secondly, using the comprehensive health data available in the Estonian Biobank, we characterized the profile of the gut microbiome in the Estonian population and identified various factors affecting the microbiome. Our study indicated that the long-term antibiotics usage has an accumulative effect on the gut microbiome composition independent of recent usage. The novelty of this result has a significant impact on the microbiome field and the future analysis need to account for such drug effects. Lastly, we considered dividing the subjects into a few distinct clusters based on their microbiome composition and evaluated the clinical applicability of such representation. We showed that although this approach is desirable in its simplicity, it is not sufficient for clinical applications. In conclusion, the microbiome science is heading towards clinical applications, but exploratory analysis is still needed. Nevertheless, the challenges ahead do not overshadow the enthusiasm.
Kirjeldus
Väitekirja elektrooniline versioon ei sisalda publikatsioone
Märksõnad
gut microflora, human, metagenomics, data analysis, health surveys