Deciphering the Impact of Exposures From the Gut Microbiome-derived Molecular Complex in Human Health and Disease
Condition: Rheumatoid Arthritis; Parkinson Disease; Healthy
MeSH terms: Parkinson Disease
Study type: Interventional

Summary: 
      The ExpoBiome project will analyze the impact of fasting on patients with Parkinsons's
      Disease (PD) or rheumatoid arthritis (RA) on a clinical level as well as the effect of
      fasting on their immune system and gut microbiota. ExpoBiome will combine metagenomics and
      other "omics" [meta-transcriptomics, meta-proteomics and (meta-)metabolomics], bioinformatic
      analyses and biostatistics under a systems biology framework to gain new mechanistic insights
      into microbiome-immune system interactions in the context of chronic diseases with
      inflammatory signatures.

      Besides a one time crossectional study of healthy participants, patients with RA and PD a
      longitudinal fasting study with two arms (RA and PD) is planned.
    

Detailed description: 
      The human gut microbiome is a complex ecosystem, which contributes essential functions to
      human physiology. Changes to the microbiome are associated with several chronic diseases
      characterised by inflammation, including neurodegenerative and autoimmune diseases.
      Microbiome-derived effector molecules comprising nucleic acids, (poly)peptides and
      metabolites are present at high levels in the gut but have so far eluded systematic study.
      This gap in knowledge is limiting mechanistic understanding of the microbiome's functional
      impact on chronic diseases such as Parkinson's Disease (PD) and rheumatoid arthritis (RA).
      Here, for the first time a combination of advanced high-resolution methodologies will be
      integrated to comprehensively identify the constituents of this molecular complex and their
      impact on the human immune system. First, a quantitative, integrated multi-omic analysis on
      microbiome samples collected from healthy individuals and patients with newly diagnosed PD or
      RA will be performes.

      Using contextualised prior knowledge (ExpoBiome Map) and machine learning methods, we will
      identify microbial molecules associated with condition-specific immunophenotypes. Second, the
      biomarker signature during a model clinical intervention (therapeutic fasting) will be
      validated and tracked to predict treatment outcomes. Third, microbes and molecules will be
      screened in personalised HuMiX gut-on-chip models to identify novel anti-inflammatory
      compounds. By providing mechanistic insights into the molecular basis of human-microbiome
      interactions, the project will generate essential new knowledge about causal relationships
      between the gut microbiome and the immune system in health and disease. By facilitating the
      elucidation of currently unknown microbiome-derived molecules, it will identify new genes,
      proteins,metabolites and host pathways for the development of future diagnostic and
      therapeutic applications.
    

Intervention name(s): Fasting
Intervention type(s): Other
Intervention description(s): Patients undergo a 5-10 day fasting period with a dietary energy supply 350-400kcal per day with fruit and vegetable juices or, if not feasible, an established fasting-mimicking diet of 600-800 kcal according to Longo et al.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Health Services Research