• The ENDOTARGET project, coordinated by Helsinki University Hospital (HUS), aims to understand mechanisms and events underlying rheumatic disease (RD) onset by exploring the relationship between gut microbiota, intestinal permeability, and systemic endotoxemia.
  • One aim is to identify drivers of chronic inflammation that determine the transition from health to pre-symptomatic and early stage of RDs.
  • ENDOTARGET combines front-line expertise from academia, hospitals and industry

To decipher the mechanisms and events triggering health-to-disease transition, the project will study the pathogenesis of RDs by:

  • conducting geographically diverse cohort studies
  • using high-throughput OMICS- based analysis for biomarker identification
  • conducting targeted clinical studies
  • performing mechanistic studies
  • conducting interventional PoC studies of diet, faecal transplantation and a gut permeability decreasing drug
  • analysing new potential drugs or nutraceuticals in vitro to cope with endotoxemia effects in target tissues.
  • The ENDOTARGET project also aims to develop a software tool (RDPT) for predicting risk of developing RD and for patient satisfaction.
  • The cohort data will be collected by HUS (Finland), UTARTU (Estonia), SERGAS (Spain) and iMM (Portugal)
  • The cohort and clinical studies will be conducted by HUS (Finland), UH (Finland), UNICAM (Italy) and iMM (Portugal)
  • Mechanistic studies will be conducted at UH (Finland), ETHZ (Switzerland) and TUW (Austria).
  • Biomarker analysis:
    • Genomic analyses by UTARTU (Estonia)
    • Proteomic and Lipidomic analyses by SERGAS/FIDIS (Spain)
    • Microbiome analysis by UH (Finland)
  • Fecal microbiota transplant interventional studies will be carried out at HUS/UH (Finland)
  • Dietary interventional study will be performed at iMM (Portugal)
  • Gut permeability studies (multicentre larazotide clinical trial) will be conducted by iMM (Portugal), HUS (Finland), UNICAM (Italy) and EBRIS (Italy)
  • AI models development analysing the microbiome association to different clinical parameters is done by NEC (Germany / Italy)
  • ML models and software tool (RDPT) for predicting RDs will be developed by SIB (Switzerland)
  • SIB will carry out research data management throughout the project
  • Regulatory and GDPR-related issues will be handled by EBRIS
  • Project outcomes and results will be disseminated and exploited by SEZ (Germany) in close collaboration with pre-existing EU-spanning networks


Objective 1

To demonstrate the relationship between microbiota, intestinal permeability, systemic endotoxemia and disease risk and to identify citizens at-risk of transitioning to osteoarthritis (OA), rheumatoid arthritis (RA), and spondylarthritis (SpA) within the next 5 years.

Objective 2

To study and demonstrate the relationships between microbiota, intestinal inflammation and permeability with systemic endotoxemia in focused cohorts of RA and SpA and in vitro models.

Objective 3

To explore mechanism by which systemic endotoxemia drives systemic inflammation and destruction of joints and promotes autoimmunity.

Objective 4

To develop algorithms to identify personalised risk factors and risk factor profiles to assess the risk of systemic endotoxemia (SE) and transition from health to disease.

Objective 5

To explore the potential of interventional approaches to modulate microbiota, gut barrier integrity and systemic endotoxemia-associated CI to reduce risk of disease onset and activity.


Outcome 1

Researchers and medical professionals understand the chronical inflammation factors triggering the health-to-disease transition and subsequently provide optimal counselling to citizens.

Outcome 2

Health care professionals have access to and employ objective health indicators of chronic inflammation for monitoring health status, establishing personalised prevention measures and improving health outcomes for citizens.

Outcome 3

Health care professionals have the scientific evidence and understanding of health-to-disease transition to develop and use improved guidelines for personalised prevention strategies to tackle chronic diseases.

Outcome 4

Citizens are better informed to actively manage their own health, have the tools to maintain their healthy status, improve their health and reduce their risk for developing chronic diseases.


The 48-months project will be executed through nine highly interdependent Work packages (WP)

This WP aims to identify features of the microbiota which promote chronic inflammation (CI) and systemic endotoxemia (SE) and increase the risk of rheumatic diseases (RD) by the analysis of population cohorts. This work sets basis for the discovery of novel biomarkers and proteomic profiles for intestinal dysbiosis, SE and RDs.

By the analysis of population cohorts and in vitro assays, WP2 aims to elucidate the association of microbiota dysbiosis, specific members of the microbiota and their effector molecules with the immune system and CI.

WP3 aims to characterize bacterial derived compounds such as lipopolysaccharide (LPS) and their molecular interactions with proteins and receptors involved in SE-related inflammatory responses.

WP4 will study new dietary and drug interventions like Larazotide in modulating the microbiota, intestinal permeability and RDs disease activity. Thereby, novel Strategies to prevent and control arthritis by interfering with the gut-joint axis will be developed.

WP5 will extract, standardise and harmonise data from multiple large population studies and prepare them for analysis. This WP is responsible for the validation of derived parameters, biomarkers and pathways by utilizing Machine learning (ML) and Artificial intelligence (AI) analysis.

WP6 will carefully handle the ethical considerations for personal, clinical and AI data. Furthermore, WP6 will handle GDPR compliance and will ensure that data is stored in a suitable robust manner.

The objective of this WP is to ensure compliance with the ‘ethics requirements’ set out in this work package.

WP7 will ensure transparent and successful dissemination, exploitation and communication, of the project’s results. This includes effective dissemination and communication of the project results to industry, media, the scientific community, end users and the general public. Furthermore, WP7 will provide exploitation support for best possible usage and sustainability of the project’s results.

The main objective of WP8 is to ensure the timely and qualitative achievement of project results through effective administration and leadership. Another focus is to ensure the quality control of project results and risk management of the project. This WP provides timely and efficient financial management of the project and the compliance with contractual commitments.

Reach out to the ENDOTARGET EU Project