The microbiome matters - decision pathway for personalized treatment of non-alcoholic fatty liver disease to prevent cardiovascular diseases (MAKSA2)
Päärahoittaja
Päärahoittajan myöntämä tuki (€)
- 20 000,00
Rahoitusohjelma
Hankkeen aikataulu
Hankkeen aloituspäivämäärä: 01.06.2023
Hankkeen päättymispäivämäärä: 31.05.2024
Tiivistelmä
PROJECT SUMMARY :
Up to 90% of obese Western population are estimated to suffer from non-alcoholic fatty liver disease (NAFLD). NAFLD has a bidirectional relationship with type 2 diabetes that can promote NAFLD progression to liver cirrhosis and cancer. To date, there are no effective long-term treatments for NAFLD. We have found that NAFLD can be partially treated with xylo-oligosaccharide (XOS) diet, with nearly half of the patients responding to the diet. Our next goal is to create the decision pathway to recognize the part of the population, which gets health benefits from XOS. Stratification of the NAFLD patients would have a large importance for treating the disease in a personalized manner to increase health and lifespan of the patients.
Preliminary data from our laboratory shows that the non-responsiveness to XOS treatment associates with the gut microbiota (GM) dysbiosis at genus level. Yet, it has not been studied to what extent the association involves specific gut microbiota species and the metabolites produced by them. However, our forthcoming publication in mBio identified specific fecal metabolites associated with NAFLD, and we expect that similar fecal metabolite signatures also associate with responsiveness to the XOS treatment. We have already done GM metagenome shotgun sequencing of our samples but the bioinformatic analyses are to be done.
The main purpose of this study is to identify the factors that predict the responsiveness of the NAFLD subjects to the prebiotic XOS dietary treatment in our existing cohort. For the identification, a multi-omics approach will be conducted. Our specific objectives are:
i) to determine which GM species, their functions, as well as fecal and serum metabolites differ between the responders and non-responders before the XOS treatment (i.e., baseline)
ii) to apply multivariate machine learning models to determine, which baseline GM species, their functions and metabolites (=biomarkers) predict the responsiveness to the XOS treatment in participants with NAFLD
The samples of the XOS treatment cohort have been already collected. The GM metagenomic shotgun sequencing data has been already produced. Here we apply funding for the downstream bioinformatic analyses of the data to determine, which microbial species and functions predict the responsiveness to the XOS treatment in terms of decreasing liver fat %. In addition, we apply funding for the metabolomic analyses of the feces and serum samples for the same purpose, as well as for the salary of a PhD student. These expected costs are all specified in the section of “Budget” below.
The proposed research will create new scientific knowledge on the diverse responses of humans to prebiotic diets that modulate the GM and dysbiosis in NAFLD. The study can validate the use of the specific GM species and metabolites as future diagnostic biomarkers for NAFLD and its’ treatment to increase the health and lifespan of the patients.
Up to 90% of obese Western population are estimated to suffer from non-alcoholic fatty liver disease (NAFLD). NAFLD has a bidirectional relationship with type 2 diabetes that can promote NAFLD progression to liver cirrhosis and cancer. To date, there are no effective long-term treatments for NAFLD. We have found that NAFLD can be partially treated with xylo-oligosaccharide (XOS) diet, with nearly half of the patients responding to the diet. Our next goal is to create the decision pathway to recognize the part of the population, which gets health benefits from XOS. Stratification of the NAFLD patients would have a large importance for treating the disease in a personalized manner to increase health and lifespan of the patients.
Preliminary data from our laboratory shows that the non-responsiveness to XOS treatment associates with the gut microbiota (GM) dysbiosis at genus level. Yet, it has not been studied to what extent the association involves specific gut microbiota species and the metabolites produced by them. However, our forthcoming publication in mBio identified specific fecal metabolites associated with NAFLD, and we expect that similar fecal metabolite signatures also associate with responsiveness to the XOS treatment. We have already done GM metagenome shotgun sequencing of our samples but the bioinformatic analyses are to be done.
The main purpose of this study is to identify the factors that predict the responsiveness of the NAFLD subjects to the prebiotic XOS dietary treatment in our existing cohort. For the identification, a multi-omics approach will be conducted. Our specific objectives are:
i) to determine which GM species, their functions, as well as fecal and serum metabolites differ between the responders and non-responders before the XOS treatment (i.e., baseline)
ii) to apply multivariate machine learning models to determine, which baseline GM species, their functions and metabolites (=biomarkers) predict the responsiveness to the XOS treatment in participants with NAFLD
The samples of the XOS treatment cohort have been already collected. The GM metagenomic shotgun sequencing data has been already produced. Here we apply funding for the downstream bioinformatic analyses of the data to determine, which microbial species and functions predict the responsiveness to the XOS treatment in terms of decreasing liver fat %. In addition, we apply funding for the metabolomic analyses of the feces and serum samples for the same purpose, as well as for the salary of a PhD student. These expected costs are all specified in the section of “Budget” below.
The proposed research will create new scientific knowledge on the diverse responses of humans to prebiotic diets that modulate the GM and dysbiosis in NAFLD. The study can validate the use of the specific GM species and metabolites as future diagnostic biomarkers for NAFLD and its’ treatment to increase the health and lifespan of the patients.
Vastuullinen johtaja
Muut hankkeeseen liittyvät henkilöt (JYU)
Päävastuullinen yksikkö
Seurantakohteet
Profiloitumisalue: Hyvinvoinnin tutkimuksen yhteisö (Jyväskylän yliopisto JYU) JYU.Well
