Research Director at INRA, Joël is Scientific Director of MetaGenoPolis (www.mgps.eu). He is the leader of the team ‘functionalities of the intestinal ecosystem’ within the Micalis Institute “Food and Gut Microbiology for Human Health” (http://www.micalis.fr/micalis_eng/Poles-and-teams/Pole-Ecosystems/FInE-Dore) and scientific board member of Microbiology Pole of the Doctoral School “Therapeutic Innovations” at Paris-XI University. Joel joined INRA in 1983 and received his PhD from the University of Illinois at Urbana-Champaign, USA, in 1988. He aims to contribute to a better understanding of the intestinal ecosystem and speed up the process of translation to support and implement therapeutic choices in the medical area, as well as science-based recommendations in preventive nutrition.
1/ What strikes you most in the evolution of research on gut microbiota and why?
I have now worked for 30 years in the field of gut microbial ecology, always trying to capture emerging technologies to improve our understanding of the gut microbiota. What strikes me most is the ‘exponential’ pace at which knowledge is built in this area. Yet unfortunately no less striking is the distance between new discoveries and their translation into practical benefits for the society.
2/ Based on your expertise for www.gutmicrobiotaforhealth.com, what is according to you the health potential of better understanding the gut microbiota in this area?
What WHO calls ‘Non Communicable Diseases’ encompasses a large number of afflictions that are all connected with the intestinal microbiota, and their epidemic rise is now considered a crucial problem for mankind. I tend to think that the rise in incidence of all these immune-mediated disorders stems from the distance we took from a natural evolutionary course, with changes in daily life, nutritional and clinical practices all bound to impact the gut microbiota. Hopefully it is still time to tackle the problem, and not only by treating the symptomatic outcomes, but also by managing the underlying microbiota alterations so as to restore the homeostasis of microbe-host crosstalk. The ambition is hence to set back Homo sapiens on the normal course of its evolution as a super-organism that, for the past 60 years or so, simply neglected its inner microbial self.
3/ How do you see the evolution of clinical applications and interventions in the field of gut microbiota?
At present we emphasize the structural assessment of the gut microbiota, with expectations in the form of diagnostic, prognostic, monitoring and stratification tools that will help in clinical management of patients. The following step should be an improved prevention of risk, which will rely on the above tools for risk detection, but also on strategies for risk alleviation. Interventions will likely remain way too empirical until we make sufficient progress in our understanding of gut ecology. That will undoubtedly lead to drastically revised concepts of gut microbiota management, so far mainly restricted to functional foods. Finally, we are only barely uncovering the intricacies of food-microbe-host crosstalk and the corresponding knowledge will open new avenues towards innovations in drug target identification and drug development.
Over the past 5 years, together with the team ‘Functionalities of the Intestinal Ecosystem’ (15 permanent INRA staff and some 15 trainees), we consolidated a nice international leadership in the field of gut microbiota for health with:
A few highlights can be summarized as follows :
Phylogenetic and metagenomic core: We demonstrated that 5% of observed bacterial species are present and abundant in a majority of the human intestinal microbiota of healthy subjects. This phylogenetic core of the normal microbiota could play a key role in intestinal homeostasis (Tap EM 2009). These results were confirmed at the level of metagenome within the EU project MetaHIT (Qin Nature 2010).
Leadership in metagenomics: The Team FInE published the first two papers on human intestinal metagenomics at INRA (Manichanh Gut 2006, Gloux AEM 2007) and contributed to 18 of the current 22 publications of INRA on quantitative and functional metagenomics since 2009.
Functional metagenomics and emergence of the MetaFun platform of MetaGenoPolis: The Team FInE developed its strategy of functional metagenomics based on the screening of activities expressed by metagenomic clones or commensal and probiotic strains towards human cell lines or selected dietary substrates, producing 13 publications and one patent.
Standards of sample handling and emergence of the Sambo platform of MetaGenoPolis: Standards of sample handling and nucleic acid preparation applied to large french (ANR-MicroObese) and European (EU-MetaHIT) cohorts provided the required quality assurance for INRA’s leadership in metagenomics. Seven publications including 5 Nature papers since 2010 and one patent benefited from this know-how.
Structural dysbiosis and alteration of microbes-host crosstalk in Crohn’s disease and obesity: Pionneer in the description of dysbiosis in Crohn’s disease, the Team FInE produced 5 publications in the evaluation period that pushed the concept beyond the sole structural alteration, showing that the bacteria-cell crosstalk was shut down (Lepage Gastroenterology 2011). Within the EU-MetaHIT and ANR-MicroObese projects, the team contributed to the recognition of species richness in obesity as a patients’ stratifier for their risk of comorbidities and ability to respond to a calory-restricted diet (Cotillard Nature 2013, Lechatelier Nature 2013).
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