In the period covering the financial report 2, the organizational and scientific foundations for the project have been successfully established. These include in a first instance the receipt of ethical approvals to perform the respective clinical studies and sample collections at the involved clinical study sites. Detailed standard operating procedures for sample collection, optimal storage, and transport have been established and applied. All study participants have been recruited. Faecal, blood, urine, and saliva samples have been collected from healthy individuals and those who have just been diagnosed with Parkinson’s disease (PD) and rheumatoid arthritis (RA) for the cross-sectional study (Objective 1: Identify) as well as for the longitudinal study (Objective 2: Intervene). Materials are also being collected for determining anti-inflammatory mechanisms in dedicated follow-up experiments (Objective 3: Validate). Sample collections (baseline and longitudinal) have been completed, forming the foundations to develop robust classification and prediction methods (Objective 1, Objective 2). A detailed description of the clinical study protocol was published in a peer-reviewed journal, and protocols for sample processing have been developed and published. A rich set of metadata, e.g. clinical lab readouts or dietary habits, of the study participants, has been collected. The necessary wet-lab procedures for obtaining extracellular biomolecules (DNA, RNA, (poly)peptides and metabolites) from the collected microbiome samples have been established and published in a peer-reviewed journal. As an extension of this method, a newly developed approach for absolute quantification of high-resolution meta-omics data has been finalized. This approach is being applied to the respective biomolecular fractions during the extraction process to generate high-resolution meta-omics data to resolve the composition, functional potential and activity of the gut microbiome as well as the effector molecules produced. Multiple manuscripts highlighting the developments and outcomes linked to the project have been published in peer-reviewed journals. These include, among others, a knowledge base (Expobiome Map) compiling the body of knowledge on interactions of microbial taxa, microbial molecules, human immune pathways, and diseases; a framework to model microbial community dynamics resolved using meta-omics data and enabling robust predictions of up to three years into the future, and in vivo results revealing how diet and bacterial curli (a protein cross-seeding with α-Synuclein) exacerbate motor performance, as well as intestinal and brain pathologies in a mouse model of Parkinson’s disease.