Vall d’Hebron has led the European macroproject DISCOvERIE (Development, diagnosis and prevention of somatic diseases and gender-related mental disorders in irritable bowel syndrome in Europe, with the aim of better understanding the relationship between irritable bowel syndrome (IBS) and associated disorders (comorbidities), both mental (such as depression or anxiety) and somatic (fibromyalgia or chronic fatigue syndrome). The study was led by the Digestive Physiology and Pathophysiology Group at VHIR and the Psychiatry, Mental Health and Addictions Group at VHIR, together with the area of Mental Health at CIBER (CIBERSAM) and the area of Liver and Digestive Diseases at CIBER (CIBEREHD), and brought together 19 healthcare institutions, universities, research centres and companies across Europe.

IBS affects more than 60 million people in Europe, many of whom experience delays in diagnosis and treatment, often due to a lack of knowledge about the causes of the disease. In addition, associated disorders influence clinical severity, affect quality of life and increase the use of healthcare, social and economic resources, yet little is known about the reasons for this relationship.

In this context, the DISCOvERIE project began in 2020 within the framework of the European research programme Horizon 2020, with funding of 6 million euros. Over five years, more than 800 participants were studied, including people with IBS with and without associated disorders, and healthy controls, to understand the factors influencing the onset and severity of comorbidities. “Our goal was to identify biomarkers that help us differentiate IBS subtypes and improve early diagnosis and treatment”, explains Dr. Javier Santos, consultant at the Digestive System Department of Vall d’Hebron University Hospital, head of the Digestive Physiology and Pathophysiology Group at VHIR and researcher at CIBEREHD.

Changes in the gut and the nervous system

By analysing different biological samples (blood, stool, urine and colon biopsies), researchers assessed the intestinal barrier, the composition of the microbiota, and the responses of the immune and nervous systems.

The results reveal that patients with IBS show increased intestinal permeability —that is, an altered intestinal wall that allows potentially harmful substances to pass through— which could contribute to digestive symptoms and inflammation. Moreover, a specific alteration of the intestinal microbiota was detected, with a reduction in butyrate-producing bacteria, a compound beneficial for gut health.

Using animal models*, the teams studied the gut–brain relationship and observed that changes in intestinal permeability are linked to neuroinflammation and anxiety.

Another key finding regarding the relationship between IBS and mental health is the identification of genome regions shared with disorders such as anxiety and depression. “These findings reinforce the idea of a bidirectional influence between the gut and the nervous system, and explain the association between digestive and psychological symptoms that we see in clinical practice”, notes Dr. Josep Antoni Ramos Quiroga, head of the Psychiatry Department at Vall d’Hebron University Hospital, head of the Psychiatry, Mental Health and Addictions Group at VHIR and researcher at CIBERSAM.

In the same vein, the project integrated digital platforms and wearable devices to monitor in real time symptoms, physical activity, sleep, stress and environmental factors. This information has helped to better understand how psychosocial and environmental triggers influence symptom variability.

Towards a personalized approach to irritable bowel syndrome

The project also highlighted sex differences, showing a higher prevalence of women with IBS who have associated disorders and distinct stress responses. “It is essential to establish personalized and innovative therapeutic approaches according to sex and comorbidities in order to improve each patient’s quality of life”, the researchers stress.

Within DISCOvERIE, a test has been developed —already commercially available for clinical research— capable of measuring this set of biomarkers and reliably identifying IBS subtypes and comorbidities. Other types of tests suitable for clinical practice are also being explored. In this regard, work is underway to create a European Reference Network for Comorbid IBS (COIBSnet) that integrates healthcare providers across Europe and facilitates the translation of scientific knowledge into clinical practice.

This document is an outcome of DISCOvERIE, a project funded with 6 million euros under the European Commission’s Horizon 2020 Research Programme (Grant Agreement No. 848228), with a duration of five years (2020–2024). The content of this document reflects only the author’s views and is his or her sole responsibility; it cannot be considered to reflect the views of the European Commission or any other EU body. The European Commission is not responsible for any use that may be made of the information it contains.

*Institutional Statement on the Use of Research Animals