Neuro-Immune Intestinal Interactions in Irritable Bowel Syndrome: decoding the hidden origins of chronic disease

The origins of chronic diseases are complex, precisely because such diseases develop progressively and stay with us over time.

In chronic diseases, such as cancer, autoimmunity, neurodegenerative diseases, Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD), genes have been identified that are associated with the disease. However, these genes alone are not sufficient to drive the diseases and often exposomes and lifestyle factors have a significant impact.

We therefore need to understand a diversity of causes, and how they combine and interplay, in order to better understand chronic disease.

Ultimately, the better we can understand the origins of chronic diseases, the better we can use this knowledge to propose both preventative and therapeutic strategies to avoid and treat chronic disease.

We now understand that causes of chronic disease include:

Genetics: How our genes code our cells, tissues, organs, development and behaviour.
Exposomes: Our environment, including microbes, chemicals, physicals and other individuals.
Lifestyle: What we eat, how active we are, interactions with friends and family, our happiness levels and other lifestyle factors.

A diversity of causes

Over the years, advances in scientific research have led us to understand more about genetics and how certain genes are associated with certain diseases. However, as multidisciplinary research improves, we are learning more about the key interplay of various factors in the generation of chronic disease.

We are seeing that genetic programming can be strongly influenced by external factors and often a chronic disease can be caused by a cocktail of internal and external causes.

Identifying the pathogenic combination of these diverse causes is the challenge we face to prevent and cure a whole range of chronic diseases.

Why Institut Pasteur?

The Institut Pasteur is a unique research institution in the way it regroups 12 departments within a relatively small campus in the middle of Paris, making it impossible not to cross paths with a variety of researchers from different disciplines.

The departments at Institut Pasteur specialise in Microbiology, Mycology, Virology, Parasitology, Immunology, Infectiology, Neurosciences, Development Biology, Structural Biology, Genetics, Global Health and Computational Biology. Between them, these departments offer all the tools and knowledge required to address the complexity of chronic diseases.

The Institut Pasteur also includes a worldwide network of 33 institutes, which enable researchers to open their work to public health issues at a global scale.

The new strategic plan of Institut Pasteur aims to take advantage of the diversity of research disciplines at the Institut Pasteur. One of the key axis of the Pasteur 2030 strategic plan is deciphering the origin of diseases, taking into account genetics, exposomes and lifestyle factors in addition to the changing environment and the importance of early life development and aging on our health trajectories.

Professor Yasmine Belkaid
President and CEO, Institut Pasteur

Yasmine Belkaid graduated with a Bachelor's and Master's degrees in biochemistry from the University of Science and Technology Houari Boumediene in Algiers, as well as a Master of Advanced Studies (DEA) from Paris-Sud University. She completed a PhD in Immunology at Paris-Sud University and the Institut Pasteur in 1996, where she studied innate immune responses to Leishmania infection.

Professor Belakid then moved to the United States for a postdoctoral fellowship in intracellular parasite biology at NIAID's Laboratory of Parasitic Diseases (NIH). In 2002, she joined the Molecular Immunology Division at Cincinnati Children's Hospital Medical Center (Ohio) before returning to NIAID in 2005 as Head of the Mucosal Immunology Unit in the Laboratory of Parasitic Diseases.

Professor Belkaid has received numerous awards and honors, including the Robert Koch Prize (2021), the Lurie Prize in Biomedical Sciences (2019), and the Sanofi-Institut Pasteur Prize (2016).

She took over as President and CEO of Institut Pasteur in Janurary 2024.

Using a multidisciplinary approach to understand diverse chronic disease origins

Gastrointestinal disorders e.g. IBS and IBD

Are associated with functional alterations of the immune system, the gut microbiota as well as the nervous system.

Skin conditions e.g. psoriasis and eczma

Are affected by the makeup of your microbiota and can get worse due to stress and changes in the microbiome or external environment.

Neurodegenerative diseases e.g. Parkinson's and Alzheimer's

New strategies are being developed to harness the peripheral immune system and the microbiota in order to fight neurodegenerative processes and associated brain inflammation.

Other diseases e.g. Cancer

Through a multidisciplinary approach, we are able to begin to explore how a diversity of causes affect a wider group of chronic diseases including things like Cancer.

Through studying a diversity of causes through multidisciplinary research at the Institut Pasteur , we can better understand a variety of chronic disease origins and ultimately propose preventative and therapeutic strategies to target and treat these diseases. For example:

Deciphering IBS and IBD

Research teams at the Institut Pasteur are currently leading a joint project on better understanding the origin of IBS and IBD. This is an excellent example of research that thrives on the joint expertise of Pasteurian researchers across disciplines. In this case; microbiology, immunology, developmental biology and neurosciences.

In this project, the researchers aim at understanding how the symbiotic microbiota, the immune system and the brain join forces to protect our intestinal health. As a result, they also look at how this tripartite crosstalk can mal-adapt and generate IBS and IBD.

The research teams are currently identifying the early life factors, within the genes and the exposome, that lead to a mal-adaptation of the growing individual and the development of intestinal pathology.

Through the use of several mouse models, the researchers have been able to begin identifying mechanisms and causalities, based on clinical observations made in human IBS and IBD patients. The next steps are, once such mechanisms and causalities are established, to return to the clinic and proposal both preventative and therapeutic strategies for patients suffering from IBS and IBD.

This ‘bedside to bench and back again’ approach is key, as different aspects of the diseases are studied either in patients or in animal models, and must be repeated over and over in the case of complex diseases, such as IBS and IBD. As a result, we are beginning to learn that it is almost certain that different combinations of genes, exposome and lifestyle lead to the same pathology.

The Project Team

Researcher Profiles

Professor Gérard Eberl

Director of Immunology

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Dr Gabriel Lepousez

Researcher in the Perception and Memory Unit

Professor Pierre-Marie Lledo

Director of Neurology

Dr Fabian Guendel

Post Doctoral Researcher in the Microenvironment and Immunity Unit

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