Guillaume Nguyen-Relation between the microbiota and the endocannabinoid system
Guillaume was a postdoctoral fellow for the Canada Excellence Research Chair on the microbiome-endocannabinoidome axis in metabolic health (CERC-MEND) from November 2019 to December 2020, under the supervision of Frédéric Raymond and Cristoforo Silvestri. His research activity consisted in the implementation of a culturomics platform for the creation of a bacterial strain bank associated with the microbiome-endocannabinoidome axis. He also initiated a project on the evaluation of the effect of compounds associated with the endocannabinoidome on microbial communities.
Guillaume is pursuing his work as a research professional at Université Laval as a member of CERC-MEND under the supervision of Vincenzo Di Marzo and Frédéric Raymond.
Francesco Tinto-Chemical and bioorganic synthesis of new endocannabinoidome mediators
Francesco conducted a two year postdoctoral fellowship (June 2018-May 2020) at the Quebec Heart and Lung Institute Research Center (CRIUCPQ). He focused on the synthesis, purification, characterization and biochemical validation of new endocannabinoidome molecules and their deuterated derivatives for detection and quantification in tissue extracts through LC/MS-MS. In fact, Francesco and other collaborators in the CERC team showed how the 15-lipoxygenase enzyme that can metabolize the endocannabinoids 2-arachidonoyl-glycerol (2-AG) and arachidonoyl-ethanolamide (AEA) into 15-HETE-glycerol and –ethanolamide respectively, likely does so with other long chain unsaturated 2-acylglycerols and acylethanolamides. He designed and synthesized monoacyl glycerols and ethanolamines in non-deuterated and deuterated form from polyunsaturated fatty acides such as LA, EPA, DHA, DPA, SDA and the corresponding metabolites. These metabolites were added to our endocannabinoidome LC/MS-MS method to allow the CERC group to detect and quantify these molecules that had never been described before. These new metabolites were detected in mice and human tissues and receptor assays are ongoing to investigate their role.
Francesco has returned to Italy and is currently passing interviews for a transition to companies active in the medicinal and organic chemistry sectors.
Claudia Manca-Endocannabinoidome studies in germ-free mice
Claudia conducted a two year postdoctoral fellowship (February 2018-January 2020) at the Quebec Heart and Lung Institute Research Center (CRIUCPQ). She investigated alterations of the eCBome in various tissues, in male and female, juvenile and adult germ free (GF) mice, which lack a microbiome, and the effect of the reintroduction of a functional gut microbiome through fecal microbiota transfer (FMT). Particularly, we showed that the small and large intestine of juvenile and adult GF male mice exhibit strong modifications in the concentrations of the lipid mediators, and in the gene expression of receptors and metabolic enzymes, belonging to the eCBome and that FMT from adult donors to age-matched GF mice led to the partial or complete reversal of many of these changes after only one week, leading us to conclude that the gut microbiome directly impacts the host eCBome (Germ-free mice exhibit profound gut microbiota-dependent alterations of intestinal endocannabinoidome signaling). The same animal model was used to investigate a potential causal-effect relationship between the presence or lack of a gut microbiome and the brain eCBome as well. Brain eCBome molecules were identified, which may play a role in the microbiota-gut-brain axis (under revision “Alterations of brain endocannabinoidome signaling in germ-free mice” Claudia Manca, Melissa Shen, Besma Boubertakh, Cyril Martin, Nicolas Flamand, Cristoforo Silvestri, Vincenzo Di Marzo).
Claudia also established several collaborations, including the research groups of professor Patrice Cani (Université Catholique de Louvain), Caroline Ménard (CERVO Brain Research Center; Université Laval) and professor Angelo Tremblay (Department of Kinesiology; Université Laval).
She has returned to Italy and is currently working in the laboratory of Physiology of Nutrition headed by professor Sebastiano Banni (University of Cagliari) where she is mainly focusing on the role of dietary lipophilic molecules and/or several physiological alterations in the modulation of lipid and energy metabolism and body composition through the consequent modification of eicosanoids, eCBome-related molecules and fatty acids.
Niokhor Dione-Culturomics and microbiome studies in MGL knockout mice
Niokhor was a post-doctoral fellow in the CERC-MEND from April 2018 to September 2019, under the supervision of Cristoforo Silvestri and Frederic Raymond. His expertise in microbiology was applied to two projects.
Installation of a culturomics platform
The aim of this project was to characterize the microbiomes studied in the CERC-MEND using a culture-based approach in order to identify and isolate unique, and potentially useful bacterial strains. This will allow for the investigation of the involvement of identified bacteria in the microbiome-endocannabinoidome axis in regulating host metabolic processes. We have already identified novel strains that we will describe soon.
Characterization of Mgll knockout mouse microbiota.
In this project, we investigated whether the loss of Monoacylglycerol lipase (MGLL) modulates the gut microbiota and their response to a high fat diet. The aim of the project was to determine if the gut microbiota are a mechanism by which Mgll-/- mice are resistant to diet induced obesity and related metabolic perturbations. Results from the mice combined with culturomics experiments support the hypothesis that the altered microbiome of Mgll-/- mice contributes to their obesity resistant phenotype, and results in part from increased levels of 2-AG and monoacylglycerols.
Niokhor is currently working as a post-doc at Stanford University in the Bioengineering department under the supervision of Prof. Michael Fischbach at the Stanford Microbiome Therapies Initiative (MITI).