The incidence and prevalence of chronic inflammatory bowel disease (IBD) continue to rise. Despite advances in biotherapies, there are still patients who escape or do not respond to treatment. New complementary nutrition strategies are being tested, and this is where the LIDETER project comes in. The probiotic Propionibacterium freudenreichii (Pf) has variations in efficacy, and we have observed that these are largely diminished by diets rich in n-6, which on the other hand partially protect against colitis. Our project aims are to determine how the interactions of linoleic (n-6) and linolenic (n-3) acids with Pf can inhibit or enhance Pf's probiotic effect, in particular by modifying Pf per se, the microbiota, the colon and the bioactive lipid contents in these 2 compartments. We will also develop a fermented milk that promotes Pf's properties, and test it as a preventive or curative treatment in colitis mouse models. Finally, we will determine whether the microbial and/or lipid profiles of IBD patients in relapse versus remission correspond to those of animals on n-6 +Pf versus n-3+Pf diets, respectively. The LIDETER project addresses the burning question of interactions between diets and probiotics. It aims to improve probiotic efficacy in IBD by combining nutrition, microbiology, lipid metabolism and the pathophysiology of colitis.

Autism spectrum disorders (ASD) are neuro-developmental disorders characterized by a lack of social skills, impaired communication and repetitive behaviours. The pathophysiological processes are still largely unknown but are thought to result from both genetic and environmental factors. Beside behavioural symptoms, a large majority of children with ASD also suffers from gastrointestinal (GI) symptoms. While the behavioural symptoms in ASD are linked to impaired brain neuronal connectivity, it is unknown whether GI symptoms stem from altered neuronal connectivity of the enteric nervous system. In addition, evidence unveiled dysbiosis of the gut microbiota as an important cofactor in ASD. Our group showed a potential causal relationship between dysbiotic gut microbiota, behavioural and GI symptoms. However, the mechanisms of microbiota-mediated effects on gut and brain are still largely unknown. We propose that extracellular vesicles (EVs) produced by bacterial microbiota serve as signaling cargo between microbiota and host organs. Our project has three main objectives. First, we will provide a comprehensive molecular profile of gut microbiota-derived EVs of children with ASD associated with clinical features. Second, we will study in cultures of enteric neurons and mouse models the effects of microbiota-derived EV from ASD children, as compared to controls, on enteric neuronal connectivity, GI functions and behaviour. Third, we will examine the interaction between host genetics microbiota-derived EV phenotype and activity on enteric neuronal connectivity, GI functions and behaviour. This proposal, based on innovative concepts, will expand our knowledge on the contribution of gut microbiota on ASD pathophysiological mechanisms. This understanding could open new avenues for diagnostics and therapeutics using EV-based treatments as “postbiotics”.

Sustaining a growing population while preserving nature is challenging, especially when climates are increasingly unpredictable. Wine is one of the main commodities of the French economy, accounting for 1.3% of total exports in 2012 (5.6 billion euros of wine exports). In the context of global change and a highly competitive international market, maintaining high production levels of fine wine while limiting chemical inputs will require biological innovations. Such breakthroughs are likely to arise from experimenting with the grape must’s microbial community, a neglected actor of winemaking which impacts many wine characteristics. Much has yet to be learned about the main wine yeast, Saccharomyces cerevisiae, which can still fail to carry out alcoholic fermentation to fruition, despite modern microbiological techniques aimed at controlling fermentations. Although there is evidence that S. cerevisiae carries specific adaptations for growing in grape must, its overall level of adaptation to grape must is unknown. This matter can only be resolved with selection experiments, which assess the effect of new genetic variation on adaptation. We propose to study the adaptive potential of S. cerevisiae in natural grape must, including their microbial communities. We will analyze the impact of i) different amount of standing genetic variation and ii) experimental horizontal gene transfers (HGT) on yeast adaptation to different biotic and abiotic environments. These two genetic mechanisms of adaptation (standing genetic variation and HGT) correspond to previously described modes of adaptation to grape must by S. cerevisiae. Specifically, adaptation in S. cerevisiae will be studied in a factorial selection experiment involving five microbial community treatments (T. delbrueckii, H. uvarum, both species, whole microbial community, or sterile grape must) and three recombinant populations of S. cerevisiae (wine strains alone, wine strains and closely related domesticated strains, or strains from all known S. cerevisiae sub-groups). The competitive fitness, fermentation traits, and genomics of adaptation will be studied in the evolved populations. The prevalence of HGT as a mechanism of adaptation to grape musts will be studied among non-Saccharomyces yeasts isolated from natural grape musts, as well as with experimental evolution in S. cerevisiae. Two strategies of experimental HGT will be implemented to test if new HGT can be beneficial for S. cerevisiae in grape must. Our findings will be applicable to oenological research because all experiments will be performed in natural grape must using species and strains isolated from that environment, instead of using single-clones with undefined evolutionary history in standard laboratory media (typical for microbial evolutionary experiments). This innovative approach will allow us to test if previous laboratory studies are transposable to complex natural environments. Our work can impact wine starter technologies by providing new alleles, allele combinations for improving wine technological traits (i.e. fermentation completion). Better knowledge of the ecological niche of wine yeasts, including the effect of biotic interactions on S. cerevisiae growth and evolution, will help stabilize alcoholic fermentations. Moreover, experimental horizontal gene transfer (eHGT) has never been studied as extensively as in our project. Our results will increase dramatically our knowledge of the prevalence and functions of horizontal gene transfers. Sequencing genomes from species isolated from grape must’s microbial communities will fill a major gap in our knowledge of these communities, including the importance of HGT. The project will benefit from our broad consortium of experts because it requires the integration of new challenging approaches (eHGT, experimental evolution in complex environments) and advanced tools (phenomics robotic platform, genomics).

In this project, we propose to set up a surface biological decontamination system based on an innovative atmospheric pressure cold plasma jet technique (called plasma bullets) and to study its effect on microbiological targets for military and civilian purposes: bacilli, spores, and cocci. The first step is to conceive and to build a discharge reactor and a high voltage pulses generator that will be used for surface decontamination experiments and for characterization of plasma bullets physical and chemical properties. A parametric study will be performed in order to optimize plasma bullets biocidal effects and to highlight plasma characteristics related to these effects. Finally, we will focus on plasma/surface interaction phenomena as a function of surface and plasma bullets properties. The consortium is composed of biologists, plasma physicists, high voltage power supply specialists, and a plasma decontamination firm.

The industrial transformation of olefins by homogeneous catalysis in the “oxo” process leads to multicomponent reaction mixtures. Their current separation by distillation, quite energy consuming, might be replaced in the chemical factory of the future by organic solvent nanofiltration (OSN) cascades with equivalent performances. CYRANO aims at the development of a simulation tool to assist the design of the most relevant cascade architecture to reach a given objective. The approach is universal aiming at secure the industrial scale-up: (i) acquisition of experimental single-stage filtration results to feed the simulation, (ii) systematic design and evaluation of cascades with internal fluid recirculation, (iii) simulation/experiment confrontation with 2 “cascade pilots” at different scales to validate the robustness of the selected approach, (iv) integration of the cascades into the overall process, (v) environmental impact assessment (LCA).