PhD Proposal: Chronic oral exposure to a cocktail of inorganic food additives: impacts on the microbiota-gut-brain axis and consequences for health

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INRAE presentation

The French National Research Institute for Agriculture, Food, and Environment (INRAE) is a major player in research and innovation. It is a community of 12,000 people with 272 research, experimental research, and support units located in 18 regional centres throughout France. Internationally, INRAE is among the top research organisations in the agricultural and food sciences, plant and animal sciences, as well as in ecology and environmental science. It is the world’s leading research organisation specialising in agriculture, food and the environment. INRAE’s goal is to be a key player in the transitions necessary to address major global challenges. Faced with a growing world population, climate change, resource scarcity, and declining biodiversity, the Institute has a major role to play in building solutions and supporting the necessary acceleration of agricultural, food and environmental transitions.

Work environment, missions and activities

You will be welcomed in the Research Center in Food Toxicology (Toxalim, UMR 1331) at INRAE in Toulouse (https://eng-toxalim.toulouse.hub.inrae.fr/), within the Endocrinology & Toxicology of the Intestinal Barrier team (ENTeRisk; https://eng-toxalim.toulouse.hub.inrae.fr/research-teams/endocrinology-toxicology-of-the-intestinal-barrier) co-led by Eric Houdeau (Research Director, INRAE) and Bruno Lamas (Research Scientist, INRAE).

Our research aims to study the fate and effects in the gut of inorganic chemical substances (primarily metals and metal oxides) used as food additives (nano- and microparticles, texturizing agents, or food pigments) or unintentionally present in food (pesticides, substances migrating from packaging). The team focuses particularly on mechanisms of dysregulation along the microbiota–immune system axis and the consequences for host health, given the bactericidal and immunotoxic potential of these substances. Our research will help different stakeholders, including food safety agencies (ANSES, EFSA), in the re-evaluation and future risk assessments regarding the use of these chemicals in food. We offer a stimulating scientific environment within a dynamic team, featuring state-of-the-art equipment and an active national and international collaborative network. 

Scientific context: The health risk associated with the dietary chemical exposome is mainly addressed through organic pollutants (dioxins, pesticides, furans), while the inorganic part is less explored, often limited to heavy metals (lead, mercury, arsenic, cadmium, nickel). However, (nano)particles (NPs) of aluminum (Al), silica (Si), iron (Fe), copper (Cu) and titanium (Ti) are commonly found in human tissues (intestine, spleen, liver), including during in utero life (via maternal-fetal transfer). They are suspected originating from common additives used quantum satis in many foodstuffs, such as Ti and Si dioxide (TiO₂, E171 in EU and SiO₂, E551), sodium aluminum silicate (Al₂O₃+SiO₂, E554), Cu-chlorophyll complexes (E141) or Fe oxides (E172). Their transplacental passage and their presence in food from childhood highlight a “long-term” exposure in the general population. In rodents, NPs of Al, TiO₂, SiO₂, Cu and Fe induce gut dysbiosis and alter immune or neurological functions. However, these NPs taken alone are not representative of inorganic additives exposing humans in mixtures (sizes/elements). Our preliminary data show that exposure since the gestation to E171 or E551 disrupts the microbiota-immune system axis, predisposes to food sensitivities (allergy or intolerance) and to metabolic disorders. As the intestine and its microbiota are exposed to a multitude of particles, studies are needed to assess the impact of additive mixtures, as ingested through the diet. The aim is to assess the effects of a cocktail composed of E141, E171, E172, E551 and E554, from gestation to adulthood, on the gut-immune system and gut-brain axes, and on the susceptibility to develop chronic diseases such as a chronic intestinal inflammation, a food allergy, or also stress-related visceral disorders (irritable bowel) or metabolic disorders (diabetes, obesity). 

This PhD project will be carried out as part of the ANR Food-Inorg project, coordinated by Bruno Lamas (UMR Toxalim, ENTeRisk), and will be conducted in collaboration with the NeuroDoL unit (UMR 1107 INSERM, Clermont-Ferrand), the Microbiota-host interactions team (Pasteur Institute, Paris), the Food Immuno-Allergy Laboratory (UMR MTS, INRAE Paris-Saclay), and the Materials Physics Group (UMR 6634, Rouen).  

Your mission will be to assess the impact of exposure to a cocktail of food additives (E141, E171, E172, E551, and E554) on the intestinal barrier, and to determine its consequences for the development of metabolic disorders and chronic inflammatory bowel diseases (IBD). Moreover, in collaboration with Frédéric Carvalho’s team (NeuroDoL Unit, Microbial Metabolites and Chronic Pain axis), you will also investigate the effects of this additive cocktail on behavior and the development of irritable bowel syndrome (IBS).

You will be more specifically in charge of:

1. Evaluate in mice the effects of chronic oral exposure to this food additive cocktail on the microbiota-gut-brain axis and on the susceptibility to develop metabolic disorders, IBD and IBS.
2. Characterize the effects of this cocktail on the microbiota, immune functions, and the intestinal epithelium using ex vivo and/or in vitro approaches, including artificial digestive systems, primary immune cells and intestinal organoids. 
3. Determine the role of the gut microbiota in the effects of this food additive cocktail through fecal microbiota transplantation experiments. 

Special conditions of activity: The project is funded by the French National Research Agency (ANR). This PhD project will be co-supervised by Bruno Lamas (Toxalim, ENTeRisk) and Frédéric Carvalho (NeuroDoL Unit). You will principally work within the ENTeRisK team (UMR 1331 Toxalim, Toulouse), and you will also conduct studies on behavior and brain functions at the NeuroDoL unit (UMR 1107, INSERM, Clermont-Ferrand; https://neurodol.fr/axe-metabolites-microbiens-et-douleurs-chroniques/). In addition to collaborations with the ANR project partners, you will also collaborate with the “Laboratoire National de métrologie et d’Essais” (LNE, Paris), as well as with various technological platforms available at Toxalim, including transcriptomics, metabolomics, flow cytometry, confocal imaging, and histology (MetaToul AXIOM, TRiX, EZOP, PHI2M).

Specific conditions of activity :

The host laboratory is classified as a Zone à Régime Restrictif (ZRR).

Recruitment is therefore subject to prior access authorization, in accordance with the regulations in force on the protection of the scientific and technical potential of the Nation.

Training and skills

Recommended training: A Master’s degree in Biology and Health

Desired knowledge: The candidate should have a solid background in digestive physiology and/or immunology. Prior experience with preclinical models (mouse) of intestinal diseases would be an advantage.

Appreciated experience: An interest in host–microbiota interactions, as well as an awareness of food safety issues related to food additives, would be considered strong assets.

Skills: The candidate should be able to analyze and synthesize data. They must be rigorous, motivated, well-organized, and capable of managing their time effectively and working as part of a team.

INRAE's life quality

By joining our teams, you benefit from (depending on the type of contract and its duration):

- up to 30 days of annual leave + 15 days "Reduction of Working Time" (for a full time);
- parenting support: CESU childcare, leisure services;
- skills development systems: training, career advise;
- social support: advice and listening, social assistance and loans;
- holiday and leisure services: holiday vouchers, accommodation at preferential rates;
- sports and cultural activities;
- collective catering.

How to apply

I send my CV and my motivation letter