The gut microbiome at the interface of human health and disease
Kuupäev
2024-09-09
Autorid
Ajakirja pealkiri
Ajakirja ISSN
Köite pealkiri
Kirjastaja
Abstrakt
Kiiresti kasvav teaduslike ja populaarteaduslike artiklite, kliiniliste uuringute ja turul müüdavate mikrobioomi toodete hulk vihjab, et huvi meie kehas esinevate mikroobide vastu on suurenenud nii teadlaskonnas kui ka ühiskonnas laiemalt. Siiski on valdkond peamiselt veel vaatlusuuringute keskne, üritades kirjeldada üldiseid muutusi ja mustreid. Ühelt poolt üritame aru saada, kuidas erinevad keskkonnafaktorid ja elustiilivalikud mõjutavad meie mikrobioomi. Teisalt soovime aga mõista, kuidas mikrobioom mõjutab meie keha toimimist. Samuti uurivad mikrobioomi valdkonna teadlased võimalusi ja kaardistavad takistusi, kuidas mikrobioomi kasutada haiguste diagnoosimiseks ja ennetuseks. Käesolev doktoritöö nendest küsimustest lähtuski.
Esiteks leidsime, et peitvere testi proovid, mida kasutatakse Eestis jämesoolevähi sõeluuringutes, on sobilikud ka mikrobioomi uuringuteks. See võib tulevikus lihtsustada populatsioonipõhist proovide kogumist ning viia läbi mikrobioomitestidega täiendatud sõeluuringuid. Teiseks näitasime, et biopangal põhinevad mikrobioomi kohordid, nagu doktoritöös esitletud Eestlaste Mikrobioomi Projekt Eesti geenivaramus, on väärtuslikud uute mikrobioomi mõjutavate tunnuste avastamiseks. Näiteks leidsime, et korduv antibiootikumide ja antidepressantide kasutamine viimase 10-aasta jooksul on oluliselt seotud muutustega mikrobioomis, isegi kui viimasel ajal pole ravimit tarvitatud. Kasutades inimene-hiir mikrobioota ülekannet näitasime, et inimeste korduv antibiootikumide kasutamine viib soolestiku limaskesta toimimise häirumiseni hiirtes, isegi kui doonorid polnud poole aasta jooksul antibiootikume tarbinud.
Kuigi mikrobioomiga on veel palju avastamist ja valdkond vajab standardiseerimist, on selles doktoritöös esitatud teadustööd juba selgeks märgiks, et mikrobioomi uurimine on kasulik ka inimtervise mõistmisel. Aina enam saame aru, et paljud ravimid lisaks antibiootikumidele mõjutavad pikaaegselt meie mikrobioomi kooslust ja seeläbi tervist. Käesoleva doktoritöö tulemused koos teiste avaldatud teadustöödega annavad ravimite määramisel alust printsiibile “nii palju kui vaja, nii vähe kui võimalik”, kuna pikaaegsed mõjud vajavad veel uurimist.
Undoubtedly, an increasing number of publications, continuous public interest, numerous clinical studies, and clinically accepted microbiome-based treatments have shown great potential in the microbiome field for improving our health. However, we are still mostly in the exploratory phase, trying to understand general patterns and changes in how and which of our lifestyle choices impact the microbiome and how the microbiome can affect our physiology. We still need to characterise factors in greater detail to understand what drives the differences between individuals. Additionally, we are trying to determine possibilities and caveats on whether using the microbiome could be helpful in improving disease diagnostics and predictive tools. The current thesis tried to tackle some of these questions. Firstly, we discovered that samples used in national colon cancer screening programs could be used to study the microbiome, which might simplify population-wide sample collections and microbiome-test-supplemented screening programs in the future. Secondly, the population cohorts, supplemented with Electronic Health Records, such as the Estonian Microbiome cohort in Estonian Biobank introduced in this thesis, are valuable for uncovering new factors influencing the microbiome. As an example, we discovered that the 10-year repeated usage of antibiotics or antidepressants is significantly associated with the changes in the gut microbiome, irrespective of recent usage. Furthermore, using human-to-mouse microbiota transplantation, we showed that a human repeated history of antibiotic use results in mucosal barrier defects in the colon of mice, even though the donors had not used antibiotics in the last 6 months. Although there is still a lot to discover and the field is still figuring out its standards, all these studies presented in this thesis indicate the important role of the gut microbiome in the interface of human health and disease. We are already increasingly understanding the long-term effects of antibiotics and other drugs on the microbiome and our health. Studies presented in this thesis, in combination with research done by others, warrant us to follow the principle of “as much as needed, as least as possible” in medication usage, as the long-term effects need further studies.
Undoubtedly, an increasing number of publications, continuous public interest, numerous clinical studies, and clinically accepted microbiome-based treatments have shown great potential in the microbiome field for improving our health. However, we are still mostly in the exploratory phase, trying to understand general patterns and changes in how and which of our lifestyle choices impact the microbiome and how the microbiome can affect our physiology. We still need to characterise factors in greater detail to understand what drives the differences between individuals. Additionally, we are trying to determine possibilities and caveats on whether using the microbiome could be helpful in improving disease diagnostics and predictive tools. The current thesis tried to tackle some of these questions. Firstly, we discovered that samples used in national colon cancer screening programs could be used to study the microbiome, which might simplify population-wide sample collections and microbiome-test-supplemented screening programs in the future. Secondly, the population cohorts, supplemented with Electronic Health Records, such as the Estonian Microbiome cohort in Estonian Biobank introduced in this thesis, are valuable for uncovering new factors influencing the microbiome. As an example, we discovered that the 10-year repeated usage of antibiotics or antidepressants is significantly associated with the changes in the gut microbiome, irrespective of recent usage. Furthermore, using human-to-mouse microbiota transplantation, we showed that a human repeated history of antibiotic use results in mucosal barrier defects in the colon of mice, even though the donors had not used antibiotics in the last 6 months. Although there is still a lot to discover and the field is still figuring out its standards, all these studies presented in this thesis indicate the important role of the gut microbiome in the interface of human health and disease. We are already increasingly understanding the long-term effects of antibiotics and other drugs on the microbiome and our health. Studies presented in this thesis, in combination with research done by others, warrant us to follow the principle of “as much as needed, as least as possible” in medication usage, as the long-term effects need further studies.
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