Deciphering the Mechanisms Of the heterogeneous Shedding of Salmonella in Chicken, and modelling the interactions between the host, the pathogen and the gut microbiota – MOSSAIC
The importance of heterogeneous shedding patterns in the context of infectious diseases is now well documented and recognized. The infected individuals that harbour and shed a given pathogen at higher concentrations than their congeners are often referred to as super-shedder, by opposite to low-shedder individuals. These super-shedders have a much higher transmission rate and thus constitute a key target for epidemiological investigation and management of diseases such as salmonellosis for which poultry constitute the major source of human contamination. However, the conditions that favour their super-shedding phenotype are poorly understood but are a prerequisite to control the reservoir of contamination within a population. As the emergence of the super- and low-shedder phenotypes are determined by the gut microbiota present before infection, and have been observed in various animal species reared in distinct environments and in strikingly diverse gut microbiota compositions, we hypothesized that while different bacterial taxa may lead to similar outcomes in terms of heterogeneous shedding, potential functional and taxonomic commonalities in the intestine should lead to these phenotypes. Thus, based on preliminary data obtained in chicken, heterogeneous shedding appears to depend on a combination of (1) specific gut microbiota features (2) mucosal immune responses parameters (3) a complex metabolites-driven dialogue between host, pathogen and microbiota and (4) several stochastic effects, including the pace and success of the gut colonization by environmental micro-organisms. In contrast, we have shown that host genetics and modification of bacterial virulence do not play a major role. In this project, we will study the causes of the Salmonella Enteritidis heterogeneous shedding in chicken. Based on different conditions known to favour one of these phenotypes by modifying the gut microbiota composition, we will compare the specific gut microbiota features, the mucosal and systemic immune response parameters and the complex metabolites-driven dialog in the intestine.
The MOSSAIC project, organized in six tasks, has three main objectives:
To provide a deeper and more integrated understanding of the heterogeneous shedding phenomenon;
To model the interactions of the partners of the biological “ménage à trois”: Salmonella-host immune response-gut microbiota, taking into account their metabolites;
To confirm by using several in vitro and in vivo experiments some hypotheses suggested by the data analyses and mathematical models.
The feasibility of our project is based on an original model of infection in isolator, which allow us to clearly identify the super- and low-shedder phenotypes by controlling animal cross contaminations. Moreover, the MOSSAIC project brings together 5 partners with complementary expertise required to carry out the work program: bacteriology, animal infection, avian immunology and metabolism, metabolomics, bioinformatics and modelling.
In a long-term perspective, the knowledge gained during the project will serve as a basis for the development of bacterial communities, which could be fed to chicks to standardize their gut microbiota and increase their resistance to pathogens in poultry production sector.
Monsieur Philippe VELGE (UMR 1282 ISP INRAE Centre Val de Loire)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
PRC Physiologie de la reproduction et des comportements
ISP UMR 1282 ISP INRAE Centre Val de Loire
MaIAGE Mathématiques et Informatique Appliquées du Génome à l'Environnement
TOXALIM Toxicologie Alimentaire
PFIE Plateforme d'Infectiologie Expérimentale
Help of the ANR 410,278 euros
Beginning and duration of the scientific project: March 2022 - 36 Months