The project

The liver and the gastrointestinal (GI) tract are closely linked. Therefore it is not surprising that an imbalance of the GI microbiome is associated with all stages of NAFLD as shown recently. BestTreat aims to disentangle the mechanistic basis of the complex interactions of microbiota, host metabolism and NAFLD by integrating emerging technologies in medicine, bioinformatics and genetic engineering. This will enable us to advance our current understanding of human-microbiota interaction in NAFLD and to develop new diagnostic and therapeutic tools to tackle NAFLD.

Our research is divided into four research work packages (WP) spanning following disciplines (I) Metabolism & Endocrinology, (II) Physiology & Biochemistry, (III) Computational & Systemsbiology, and (IV) Microbiology & Bioengioneering each one is led by a BestTreat consortium member with a world class scientific record in the field:

• WP 2: Human Cohorts & Mice Model: Discover associations and the predictive role of the gut microbiota and exercise onto NAFLD
• WP 3: Mechanistic Studies of Microbiome-Host Interaction: Discover serum biomarkers and exercise responsive microbiota relevant for prognosis of NAFLD
• WP 4: Big Data Analysis of the Gut Microbiota: Model the associations between microbial community parameters and NAFLD progression state by integrating meta-omics datasets
• WP 5: Phenotyping, Engineering & Characterisation: Identify, characterise and culture strains for microbiome therapeutics. Validate best strains in vivo and ex vivo

AMC and UEF will perform clinical intervention studies, such as high intensity physical exercise, to examine whether the metabolic benefits of physical exercise are mediated in part by altered gut microbiota. At HKI, Afekta and Clinical Microbiomics (CliM) we will push the limits of integrated data analysis, by moving away from the questions which microbes comprise the community and what are they capable of doing (metagenomics), to how the community can, in effect, improve metabolic homeostasis (metatranscriptomics, metabolomics, cytokines, inflammatory markers). For this objective we access the biobank at Shanghai 6^th People's Hospital consisting of blood and stool samples from 2903 subjects at risk of NAFLD of whom some develop liver damage aver the screening period. At DTU we will develop selective cultivation methods for establishing microbial strain collections from gut microbe samples associated with therapeutic monitoring of NAFLD and develop a new synthetic biology tool box. Research at RUG aims to improve our ability to genetically modify gut residents for in situ microbiome engineering and targeted antibiotic treatment. We will validate the microbiome therapeutic targets by using humanised and germ-free mice, stem cell lines and artificial gut systems that will help to assess whether an altered microbiota translates to alter host physiology, this work will be performed at Chr. Hansen (ChH, AMC, UEF and Gubra.
The active participation of end-users in our consortium (ChH, Gubra, Afekta, CliM) ensures that the project remains aligned to industry needs and regulatory frameworks for biotherapeutics. To complement the research programme we offer a bespoke training series. We get support from technology assessment and communication leaders (Biofaction, CSBJ, DK4),