Impact Of The Gut Microbiota On Host Cells Energy Metabolism: Role In Health And In Inflammatory bowel disease

Project Information

ENERGISED

Grant agreement ID: 101043802

DOI

10.3030/101043802

EC signature date 15 April 2022

Start date 1 September 2022

End date 31 August 2027

Funded under

• European Research Council (ERC)

Total cost

€ 1 999 265,00

EU contribution

€ 1 999 265,00

Coordinated by

SORBONNE UNIVERSITE
France

Periodic Reporting for period 1 - ENERGISED (Impact Of The Gut Microbiota On Host Cells Energy Metabolism: Role In Health And In Inflammatory bowel disease)

Reporting period: 2022-09-01 to 2025-02-28

Summary of the context and overall objectives of the project

Inflammatory bowel diseases (IBD), like Crohn’s disease and ulcerative colitis, are conditions where the immune system wrongly attacks the gut, causing inflammation. These diseases have become much more common in Western countries recently, likely due to environmental factors. Even with new treatments, many patients still struggle to control their symptoms, which affects their quality of life and creates economic challenges.
To improve treatment, we need to understand these diseases better and find new treatment targets. The gut microbiota (the community of microorganisms living in our intestines) plays a significant role in IBD. Changes in the energy metabolism of gut and immune cells are also thought to be involved. Normally, our immune system recognizes and responds to microbes through specific patterns or molecules. However, energy metabolism is crucial for an appropriate immune response, and new research suggests that gut microbiota can directly influence this process.
The ENERGISED project aims to:
Identify the microorganisms and their by-products that affect energy metabolism in host cells.
Understand how changes in gut microbiota impact energy metabolism in IBD.
Develop new treatments based on manipulating gut microbiota to improve energy metabolism in IBD patients.
This project is complex, involving various fields like microbiology, immunology, metabolism, and medicine, and uses advanced technologies. It also has the potential to benefit society by discovering new treatment strategies.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

1. We screened over 100 gut microbiota-derived metabolites and identified several candidates acting on immune cells’ energy metabolism.
2. Among the identified metabolites, we next focused on 2 metabolites, which act on CD4+ T cells and macrophages, respectively. We deciphered their mechanisms of action in depth and showed they have an effect in vivo in mice both at steady state and in inflammatory contexts. Finally, we also ensured our results have some human relevance by analysing data from cohorts of patients with Inflammatory bowel diseases.
3. We showed that the gut microbiota impacts host immune cells’ energy metabolism in vivo. This was shown in mice using germ-free and antibiotics-treated animals. More importantly, we demonstrated that it is also true in humans.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The three significant achievements described above clearly advance the research field beyond the state of the art. The last result on the effect of the gut microbiota on energy metabolisms of immune cells in humans is a breakthrough in the gut microbiome and immunity fields. This last result was based on our initial hypothesis but, to our knowledge, this is the first time it has been demonstrated in such a manner. We think it will be of high interest to the scientific community.