Periodic Reporting for period 1 - IMMEDIATE (Imminent Disease Prediction and Prevention at the Environment Host Interface)
Reporting period: 2023-01-01 to 2024-06-30
In Europe, rapidly changing environmental factors such as unhealthy diet, physical inactivity, climate change as well as increased work-related stress are the main drivers of many non-communicable diseases. These modifiable factors can trigger and maintain chronic inflammation, a common process in many diseases. Long periods of covert and subclinical inflammation may proceed organ damage and result in clinical manifestation as chronic kidney disease (CKD), cardiovascular disease (CVD) or brain damage. It is increasingly recognized that the gut is a major driving force that orchestrates the regulation of inflammatory responses and maintains the balance of pro- and anti-inflammatory forces. IMMEDIATE focuses on studying plasticity, resilience, redundancy and deflection of the diet-microbiome-metabolite-immune axis (a blind range of imminent disease) and utilize this axis as a sensor for health-to-disease transition at the individual level.
The IMMEDIATE goal will be achieved by identifying biomarkers and actionable factors, conducting a proof-of-concept study on hospital physicians to evaluate Akkermansia muciniphila, by mapping biomarkers using Omics and single-cell technologies and by providing individuals tools to track lifestyle and dietary habits.
To achieve these IMMEDIATE goals, we will
1) create IMMEDIATE observatory for chronic inflammation, a model for chronic inflammatory factors triggering the health-to-disease transition
2) generate a database of omics profiles in health and diseases and omics profiles linked to the transition of health to CVD, CKD, type 2 diabetes (T2D) and brain damage
3) generate a list of actionable risk/resilience factors linked to inflammation-driving transition of health to CVD, CKD, T2D and brain damage, which can be used to develop novel prevention guidelines or health care program
4) evaluate anti-inflammatory effects of postbiotics Akkermansia muciniphila as well as its effects on mental and somatic health
5) and, finally, develop IMMEDI-APP, a personalized APP for dynamic monitoring and individualized provision of lifestyle/dietary recommendations.
The IMMEDIATE goal will be achieved by identifying biomarkers and actionable factors, conducting a proof-of-concept study on hospital physicians to evaluate Akkermansia muciniphila, by mapping biomarkers using Omics and single-cell technologies and by providing individuals tools to track lifestyle and dietary habits.
To achieve these IMMEDIATE goals, we will
1) create IMMEDIATE observatory for chronic inflammation, a model for chronic inflammatory factors triggering the health-to-disease transition
2) generate a database of omics profiles in health and diseases and omics profiles linked to the transition of health to CVD, CKD, type 2 diabetes (T2D) and brain damage
3) generate a list of actionable risk/resilience factors linked to inflammation-driving transition of health to CVD, CKD, T2D and brain damage, which can be used to develop novel prevention guidelines or health care program
4) evaluate anti-inflammatory effects of postbiotics Akkermansia muciniphila as well as its effects on mental and somatic health
5) and, finally, develop IMMEDI-APP, a personalized APP for dynamic monitoring and individualized provision of lifestyle/dietary recommendations.
During the first 18 months, IMMEDIATE has drafted and collectively revised the actionable guidelines and data management plan (DMP) as a framework for combining datasets from well-characterized cohorts, multi-omics and IMMEDI-APP. It facilitates data curation in each work package (WP) as well as the planned downstream data analysis. This framework has been shared to all IMMEDIATE partners, and a workshop was carried out for detailed discussion. All partners have dynamically given feedback and suggestions that are incorporated into the revised version of the framework to accommodate the latest project exigencies. To assist towards the task of developing chronic inflammation observatory, we are setting up a robust systems and software architectures for machine learning and modelling systems. A consortium-wide training in the form of a seminar/workshop is planned. In addition, meanwhile we utilize existing datasets from the Berlin Long-Term Evaluation of Vascular Events (BeLOVE) cohort to generate models of inflammation-associated chronic diseases, which can be explored as further validation opportunity for IMMEDIATE holistic datasets.
To ensure the quality of longitudinal datasets obtained from high-dimensional (i.e. OLINK Inflammation 92 and CyTOF) and omics analyses (i.e. metabolomics, metagenomics, scRNA-seq and scATAC-seq), and to allow a harmonization and comparison between IMMEDIATE and existing datasets (e.g. BeLOVE), new standardized workflows were established for high-dimensional and multi-omics analyses in IMMEDIATE. Although this step caused delay in our progress, this strategy will finally result in robust models for chronic inflammation observatory and further facilitate a development of methods to mitigate chronic inflammation such as healthy diet, stress reduction techniques and other methods to enhance resilience as well as tailored dietary recommendations. Peripheral blood samples of the kidney transplantation cohort (KTX360°) were successfully measured by CyTOF using the standardized protocol optimized for IMMEDIATE.
In the interventional study, pasteurized Akkermansia muciniphila (PAM) capsules were already produced and applied to the study participants. About 75% of the planned participants (i.e. 155 out of 200) have already been recruited and biosamples were collected. Working in a close collaboration with the IMMEDI-APP team, the PAM study has collected parameters associated with somatic and mental signs of chronic stress via the APP at higher frequency (weekly) than those collected at each visit (monthly) with the full set of the questionnaires.
Altogether during this first reporting period, we have focused on streamlining and standardizing all study protocols, generating IMMEDI-APP, setting up IMMEDIATE DMP and systems and software architectures for downstream data integration and analysis, as well as performing PAM study. These procedures will facilitate our next steps to identify shared and non-shared signatures of chronic inflammation across different diseases as well as to generate the chronic inflammation observatory.
To ensure the quality of longitudinal datasets obtained from high-dimensional (i.e. OLINK Inflammation 92 and CyTOF) and omics analyses (i.e. metabolomics, metagenomics, scRNA-seq and scATAC-seq), and to allow a harmonization and comparison between IMMEDIATE and existing datasets (e.g. BeLOVE), new standardized workflows were established for high-dimensional and multi-omics analyses in IMMEDIATE. Although this step caused delay in our progress, this strategy will finally result in robust models for chronic inflammation observatory and further facilitate a development of methods to mitigate chronic inflammation such as healthy diet, stress reduction techniques and other methods to enhance resilience as well as tailored dietary recommendations. Peripheral blood samples of the kidney transplantation cohort (KTX360°) were successfully measured by CyTOF using the standardized protocol optimized for IMMEDIATE.
In the interventional study, pasteurized Akkermansia muciniphila (PAM) capsules were already produced and applied to the study participants. About 75% of the planned participants (i.e. 155 out of 200) have already been recruited and biosamples were collected. Working in a close collaboration with the IMMEDI-APP team, the PAM study has collected parameters associated with somatic and mental signs of chronic stress via the APP at higher frequency (weekly) than those collected at each visit (monthly) with the full set of the questionnaires.
Altogether during this first reporting period, we have focused on streamlining and standardizing all study protocols, generating IMMEDI-APP, setting up IMMEDIATE DMP and systems and software architectures for downstream data integration and analysis, as well as performing PAM study. These procedures will facilitate our next steps to identify shared and non-shared signatures of chronic inflammation across different diseases as well as to generate the chronic inflammation observatory.
Although at this project phase no results were yet obtained, there are several important achievements during the first reporting period:
• Systems and software architectures for integration and analysis of datasets with different modality and formats. This novel system will assist the combination of clinical parameters including information about diet and lifestyle and multi-omics datasets.
• Successful registration and initiation of proof-of-concept study using PAM.
• Establishment of IMMEDI-APP to collect parameters associated with somatic and mental signs of chronic stress
• Systems and software architectures for integration and analysis of datasets with different modality and formats. This novel system will assist the combination of clinical parameters including information about diet and lifestyle and multi-omics datasets.
• Successful registration and initiation of proof-of-concept study using PAM.
• Establishment of IMMEDI-APP to collect parameters associated with somatic and mental signs of chronic stress