Metabolic diseases from the point of view of the gut bacterial motility and mucus barrier

Informations projet

MEDMOTILUS

N° de convention de subvention: 101024357

DOI

10.3030/101024357

Projet clôturé le 30 Novembre 2023

Date de signature de la CE 19 Avril 2021

Date de début 1 Juin 2022

Date de fin 31 Mai 2024

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 184 707,84

Contribution de l’UE

€ 184 707,84

Coordonné par

SORBONNE UNIVERSITE
France

Periodic Reporting for period 1 - MEDMOTILUS (Metabolic diseases from the point of view of the gut bacterial motility and mucus barrier)

Période du rapport: 2022-06-01 au 2024-05-31

Résumé du contexte et des objectifs généraux du projet

Metabolic disorders, as chronic non-communicable diseases, are among the highest European and worldwide biomedical research priorities. Their prevalence is rising, and they may also increase the risk of many comorbidities, including cardiovascular diseases. The gut microbiota and environment are usually altered in subjects with metabolic disorders. The mucus barrier protects the host mucosa from the bacteria, reducing the possibility of interaction and, consequently, host responses. Thus, the mucus barrier and microbiota are potential therapeutic targets to improve the metabolism status of patients. It will also be important to identify useful biomarkers of the gut mucus/microbiota motility in metabolic diseases for further research on diagnosis and monitoring to reduce long-term complications.

MEDMOTILUS project aimed to understand better the relationship between gut mucus/microbiota homeostasis and metabolic status, specifically regarding bacterial motility. In addition, the project had secondary objectives, which included evaluating new methods for studying the gut environment and validating an animal model for metabolic diseases. The project was designed with a multi-omics and multidisciplinary approach that involved a large human cohort and animal models.

There were three main conclusions of this project. The first is that healthy and lean subjects showed greater gut bacterial motility potential without adverse metabolic alterations than obese subjects. The second is that the pig could be a better biomedical model to study the gut mucus barrier and bacterial motility than the mouse. The last is the confirmation of the mucus as a useful tool for studying bacterial motility.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

A review of metagenomics functional knowledge related to bacterial motility was conducted to select the signatures of interest to study. Their presence and quantification were evaluated using a large human cohort with different severity of metabolic alterations. The higher motility gene abundance found in lean subjects has been reinforced by metaproteomics data and the measurement of the pro-inflammatory potential of flagellin. The evaluation of the mouse model with similar methods didn’t show the same pattern as the human results. The microbiota composition of the group with metabolic alteration differed markedly from the obese human results. Another animal model with a larger sample quantity, such as the pig, is needed to assess whether a possible confounding factor could hinder the study of bacterial motility at the flagellin level. Changes made to the original project design have enhanced the quality of the project.

Piglet intestinal mucus was extracted and purified to do a physic-chemical characterization. Previous methods to analyze the bacteria 3D movement were adapted to work with mucus. New methods were developed to study the penetration of bacteria in the mucus. The last pig experiment was carried out to evaluate the mucus barrier and bacterial motility in a large animal model with higher adiposity. The early termination of the project has not allowed to finish the analyses before the end of the project.

Presentations at several scientific meetings and two open-access publications have been the main points of dissemination with other researchers, health professionals, and Industry. Two supplemental publications are expected. The researcher has also participated in events to raise general public awareness of the importance of science and as an MSCA ambassador.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The project has obtained two main contributions. The first is to show the relationship of flagellar motility in individuals with metabolic diseases at different molecular levels and the need for animal models to clarify some issues. The second is the possibility of using porcine mucus to study bacterial movement and penetration.

The results obtained in this project can help to understand the mechanisms underlying health. They may influence the current approach toward the pro-inflammatory potential effects of bacteria in metabolic disorders and the inclusion of an expanded range of motility functions in further studies. Data and resources generated during the project may be a basis for further developing potential tests or devices to help diagnose patients with metabolic disorders and make treatment decisions that improve the sustainability of healthcare systems. However, further research continuing the MEDMOTILUS project is needed to achieve that step.

Summary of project results