The preventive role of gut microbiota modulating prebiotic xylo-oligosaccharides in non-alcoholic fatty liver disease

Suolistomikrobiston koostumus on yhdistetty ei-alkoholiperäiseen rasvamaksatautiin (NAFLD). Erityisesti Faecalibacterium prausnitzii -bakteerin runsas määrä suolistossa voi edistää maksan terveyttä. Koska tätä bakteeria ei ole vielä hyväksytty hoitomuodoksi ihmisillä, on tärkeää löytää vaihtoehtoisi...

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Main Author: Honkanen, Marjaana
Other Authors: Matemaattis-luonnontieteellinen tiedekunta, Faculty of Sciences, Bio- ja ympäristötieteiden laitos, Department of Biological and Environmental Science, Jyväskylän yliopisto, University of Jyväskylä
Format: Master's thesis
Language:eng
Published: 2020
Subjects:
Online Access: https://jyx.jyu.fi/handle/123456789/73862
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author Honkanen, Marjaana
author2 Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_facet Honkanen, Marjaana Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä Honkanen, Marjaana Matemaattis-luonnontieteellinen tiedekunta Faculty of Sciences Bio- ja ympäristötieteiden laitos Department of Biological and Environmental Science Jyväskylän yliopisto University of Jyväskylä
author_sort Honkanen, Marjaana
datasource_str_mv jyx
description Suolistomikrobiston koostumus on yhdistetty ei-alkoholiperäiseen rasvamaksatautiin (NAFLD). Erityisesti Faecalibacterium prausnitzii -bakteerin runsas määrä suolistossa voi edistää maksan terveyttä. Koska tätä bakteeria ei ole vielä hyväksytty hoitomuodoksi ihmisillä, on tärkeää löytää vaihtoehtoisia keinoja sen luonnollisen määrän lisäämiseksi suolistossa. Tässä tutkimuksessa selvitettiin, voiko ruokaan lisättävillä ksylo-oligosakkarideilla (XOS) lisätä F. prausnitzii - bakteerin määrää suolistossa ja siten ehkäistä NAFLD:n kehittymistä. Lisäksi tutkittiin, välittyvätkö XOS:n mahdolliset vaikutukset maksaan rasva- aineenvaihdunnan, insuliinisignaloinnin tai tulehdusvasteen muutosten kautta. Tutkimuksen näytteet saatiin eläinkokeesta, jossa rasvaisella tai vähärasvaisella ruokavaliolla olleiden rottien ruokaan joko lisättiin tai ei lisätty XOS:ia 12 viikon ajan ennen lopetusta. F. prausnitzii -bakteerin määrää suolistossa sekä geenien ja signalointiproteiinien ilmentymistasoja maksassa ja epididymaalisessa rasvakudoksessa tutkittiin kvantitatiivisella polymeraasiketjureaktiolla ja vasta-aineiden avulla proteiininäytteistä. Maksan rasvapitoisuus määritettiin Oil Red O –värjäyksellä ja rasvojen uutolla. Rasvainen ruokavalio aiheutti NAFLD:n rotille ja XOS lisäsi F. prausnitzii -bakteerin määrää suolistossa molemmilla ruokavalioilla. XOS vähensi maksan rasvoittumista rasvaisella ruokavaliolla rasvahappojen hapettumista katalysoivan entsyymin, β-hydroksiasyyli-KoA-dehydrogenaasin, lisääntyneestä aktiivisuudesta johtuen. XOS kuitenkin lisäsi epididymaalisen rasvakudoksen tulehdusta. Tulosten perusteella XOS on potentiaalinen prebiootti, jota voisi käyttää maksan rasvoittumisen ehkäisemisessä. XOS:n mahdollisia haitallisia sivuvaikutuksia tulisi kuitenkin tutkia tarkemmin. Recently, the gut microbiota composition has been linked to non-alcoholic fatty liver disease (NAFLD). Especially the abundance of Faecalibacterium prausnitzii in the gut has been shown to improve hepatic health. Because this bacterium is not yet accepted for treatment purposes in humans, it is important to find alternative ways to increase its natural abundance in the gut. The aim of this study was to determine whether xylo-oligosaccharide (XOS) supplementation increases the abundance of F. prausnitzii in the gut of rats and thus prevents the development of NAFLD and whether the possible effects of XOS are due to alterations in lipid metabolism, insulin signaling or inflammatory response. The samples used in this thesis were derived from an animal experiment in which rats were fed with high- fat or low-fat diet, supplemented or not with XOS for 12 weeks, and then euthanized. The amount of F. prausnitzii in the gut samples was determined with quantitative polymerase chain reaction (qPCR). Hepatic lipid content was studied with lipid extraction and Oil Red O staining of liver sections. The expression levels of genes and signaling proteins in liver and epididymal adipose tissue were studied by qPCR and western blot, respectively. The results show that high-fat diet caused NAFLD to the rats and XOS increased the abundance of F. prausnitzii on both diets. XOS decreased hepatic lipid content on the high-fat diet due to the increased activity of β-hydroxyacyl-CoA dehydrogenase, a rate-limiting enzyme of fatty acid oxidation. However, XOS increased epididymal adipose tissue inflammation on the high-fat diet. Based on these results, XOS is a potential prebiotic that could be used to prevent hepatic fat accumulation but the possible adverse side effects of XOS should be studied more closely.
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Tutkimuksen n\u00e4ytteet saatiin el\u00e4inkokeesta, jossa rasvaisella tai v\u00e4h\u00e4rasvaisella ruokavaliolla olleiden rottien ruokaan joko lis\u00e4ttiin tai ei lis\u00e4tty XOS:ia 12 viikon ajan ennen lopetusta. F. prausnitzii -bakteerin m\u00e4\u00e4r\u00e4\u00e4 suolistossa sek\u00e4 geenien ja signalointiproteiinien ilmentymistasoja maksassa ja epididymaalisessa rasvakudoksessa tutkittiin kvantitatiivisella polymeraasiketjureaktiolla ja vasta-aineiden avulla proteiinin\u00e4ytteist\u00e4. Maksan rasvapitoisuus m\u00e4\u00e4ritettiin Oil Red O \u2013v\u00e4rj\u00e4yksell\u00e4 ja rasvojen uutolla. Rasvainen ruokavalio aiheutti NAFLD:n rotille ja XOS lis\u00e4si F. prausnitzii -bakteerin m\u00e4\u00e4r\u00e4\u00e4 suolistossa molemmilla ruokavalioilla. XOS v\u00e4hensi maksan rasvoittumista rasvaisella ruokavaliolla rasvahappojen hapettumista katalysoivan entsyymin, \u03b2-hydroksiasyyli-KoA-dehydrogenaasin, lis\u00e4\u00e4ntyneest\u00e4 aktiivisuudesta johtuen. 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spellingShingle Honkanen, Marjaana The preventive role of gut microbiota modulating prebiotic xylo-oligosaccharides in non-alcoholic fatty liver disease Faecalibacterium prausnitzii hepatic lipid accumulation Solu- ja molekyylibiologia Cell and molecular biology 4013 rasvakudokset rasvamaksa suolistomikrobisto prebiootit adipose tissues fatty liver gastrointestinal microbiota prebiotics
title The preventive role of gut microbiota modulating prebiotic xylo-oligosaccharides in non-alcoholic fatty liver disease
title_full The preventive role of gut microbiota modulating prebiotic xylo-oligosaccharides in non-alcoholic fatty liver disease
title_fullStr The preventive role of gut microbiota modulating prebiotic xylo-oligosaccharides in non-alcoholic fatty liver disease The preventive role of gut microbiota modulating prebiotic xylo-oligosaccharides in non-alcoholic fatty liver disease
title_full_unstemmed The preventive role of gut microbiota modulating prebiotic xylo-oligosaccharides in non-alcoholic fatty liver disease The preventive role of gut microbiota modulating prebiotic xylo-oligosaccharides in non-alcoholic fatty liver disease
title_short The preventive role of gut microbiota modulating prebiotic xylo-oligosaccharides in non-alcoholic fatty liver disease
title_sort preventive role of gut microbiota modulating prebiotic xylo oligosaccharides in non alcoholic fatty liver disease
title_txtP The preventive role of gut microbiota modulating prebiotic xylo-oligosaccharides in non-alcoholic fatty liver disease
topic Faecalibacterium prausnitzii hepatic lipid accumulation Solu- ja molekyylibiologia Cell and molecular biology 4013 rasvakudokset rasvamaksa suolistomikrobisto prebiootit adipose tissues fatty liver gastrointestinal microbiota prebiotics
topic_facet 4013 Cell and molecular biology Faecalibacterium prausnitzii Solu- ja molekyylibiologia adipose tissues fatty liver gastrointestinal microbiota hepatic lipid accumulation prebiootit prebiotics rasvakudokset rasvamaksa suolistomikrobisto
url https://jyx.jyu.fi/handle/123456789/73862 http://www.urn.fi/URN:NBN:fi:jyu-202101281321
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