Role of peptidoglycan produced by the microbiota in host physiology
Responsible of the project: Ivo GOMPERTS BONECA
Coordinating institution: Institut Pasteur
Peptidoglycan; Brain; Sleep patterns; Gut; Immune system; Inflammatory bowel disease; Joint inflammation; Malnutrition; Colon cancer; Food additives; Emulsifiers
- Total cost: 11,31M€
- Starting date: 01/07/2025
- Duration: 5 years
- Reference : ANR-24-PESA-0014
• Overall objective:
Chronic inflammatory diseases are one of the greatest challenges facing Western societies. The link between these diseases and our lifestyles is increasingly being questioned, particularly the impact on our microbiome. The loss of microbiome diversity is associated with a loss of homeostasis and balance between us and our microbes due to a disruption in the dialogue between our cells/organs and our microbes.
• Scientific and societal issues:
Our microbes constantly communicate with our cells/organs via molecules. Peptidoglycan, the major component of the bacterial cell wall, is one of these molecules that is recognized by various Nod family receptors, including Nod1 and Nod2. Variants of these receptors are involved in chronic inflammatory diseases such as Crohn’s disease or asthma, demonstrating the important role of this molecular dialogue in maintaining the balance between us and our microbes. However, our knowledge of this dialogue and its impact on our physiology is still in its infancy. The main objective of the PGNshapingHOST project is to study in detail this molecular dialogue in healthy individuals and the consequences when it is disrupted in the context of chronic inflammatory diseases.
• Project focuses:
The PGNshapingHOST project focuses on three areas:
1) Development of molecular tools and methodologies to monitor the fate of peptidoglycan produced by the microbiome in the host, i.e., the chemical nature of the peptidoglycan fragments absorbed and disseminated within the host, the detoxification/metabolization mechanisms of these fragments, and the target cells/organs of these fragments.
2) Study of the biological effects of these fragments locally on the intestine, on the liver (and how it participates in its dissemination and detoxification), and on the nervous system (sleep regulation and nociception in the intestine).
3) Study of the impact of disturbances in this dialogue (nutritional, genetic, bacteriological) on the role of peptidoglycan in chronic inflammatory diseases where it is strongly involved, i.e. Crohn’s disease, colorectal cancer and juvenile idiopathic arthritis.
- Coordinating institution: Institut Pasteur
- Partner institutions: Université de Lille, Sorbonne Université, École Normale Supérieur de Lyon, Inserm
