PhD Thesis project: Effect of phosphorus on immune system and the gut microbiota interaction and their consequence on the development of inflammatory diseases.

Increasing evidences from human and animal studies show that nutritional and microbial factors during a critical window of opportunity early in life are required to prevent pathologies development later in life such as allergy, inflammatory bowel diseases, cancer and metabolic-related diseases. Recently, it has been revealed that a vigorous immune response induced by intestinal microbiota during weaning period is required to prevent increased susceptibility to chronic inflammatory diseases in adult mice (Al Nabhani et al., Immunity 2019). Phosphorus (P) is an essential nutrient for both microbes and their host, as it is involved, for example, in bone formation, energy metabolism, cellular signaling and stabilization of cell membranes.

Given the close relationship between specific microbial metabolites and expression of cytokines (Metzler-Zebeli et al, J Nutr 2012), interactions between intestinal microbiota including their metabolic activities, the integrity of the epithelial barrier function, the immune system, and the P content of the diet can be assumed. Furthermore, results from other vertebrate species indicate that dietary deficiency of P may negatively affect lymphocyte function, cytokine secretion and anti-body production. Stratification and compartmentalization, for example, are the main immunological mechanisms preventing the host from colonization with intestinal pathogens, and both strongly depend on IgA production and cytokine secretion by intestinal immune cells. In an immune-compromised host, however, these mechanisms might be reduced. Reduced lymphocyte function, because of low P availability, might therefore negatively affect the host’s ability to prevent intestinal colonization by pathogens.

Our proposal aims to address the following questions 1) to define the microbial factors mediated by the P dietary during early in life that predict pathological imprinting; 2) to determine the immune cells that carry a healthy or pathological imprinting at long-term under P dietary ; 3) to identify at molecular, metabolic and epigenetic level the underlying mechanisms of the immune memory induced by P treatment; 4) to develop therapeutic measures that induce a healthy weaning reaction or target the pathological imprinting. To this end, we will use transgenic mouse and gnobiotic model, reversible bacterial colonization, metabolomics, epigenetic, DNA cytosine methylation, single-cell transcriptome and high-throughput sequencing technologies. These studies will decipher how nutrition control microbiota and instruct the immune system and impact inflammatory diseases in adulthood and thereby will provide targets for preventive and therapeutic measures against diseases development.

Reference:

Al Nabhani, Z. et al. A Weaning Reaction to Microbiota Is Required for Resistance to Immunopathologies in the Adult. Immunity 50, 1276–1288.e5 (2019)

Metzler-Zebeli BU, Ga ?nzle MG, Mosenthin R,et al. (2012)Oatb-glucan and dietary calcium and phosphorus differen-tially modify intestinal expression of proinflammatorycytokines and monocarboxylate transporter 1 and cecalmorphology in weaned pigs.J Nutr142, 668 – 674

Conditions of Access and Application:

https://um6p.ma/en/formation-doctorat