LabCom_2022 - V1 - Laboratoires communs organismes de recherche publics – PME/ETI - Edition 2022 - Vague 1

Intestinal microbiota and metabolic diseases : a unique in vitro gut model to boost the development of new nutritional strategies – MIMETiv

Submission summary

Non-alcoholic steatohepatitis (NASH) and dyslipidemia are highly prevalent diseases, precursors of various life-threatening pathologies (cirrhosis, atherosclerosis). Pathophysiology of the aforementioned diseases is complex, but both involve alterations in carbohydrate and/or lipid metabolism, and associated with disturbances of the intestinal microbiota. To date, data linking metabolic disorders and gut microbiota have only been envisioned through stool analysis and it appears relevant to extend this work to the microbiota harbored in the small intestine, which represents the major site of digestion/absorption of. carbohydrates/lipids in humans. Beside the non-existence of drug therapies (NASH) or restriction by multiple side effects (dyslipidemia), nutritional strategies, in particular those related to plant extracts, appear very useful for a comprehensive and preventive management of these diseases. The preclinical evaluation of active plant compounds can be investigated in rodents, but this approach remains limited by differences between the diet and digestive physiology of animals and humans (especially in terms of gut microbiota) and by increasing regulatory and societal constraints. An alternative of choice consists in using artificial digestive systems, provided their relevance is ensured when compared to the in vivo situation. In this frame, MIMETiv project associates the MEDIS laboratory from Université Clermont Auvergne (UCA), which has a long-standing expertise in in vitro simulation of the human digestive environment, and the company Valbiotis, which is developing innovative strategies to fight against metabolic disorders, with therapies based on the combination of plant biomolecules (TOTUM-448 and -070 for NASH and dyslipidemia, respectively). The primary objective of the LabCom project is to optimize and validate the ESIN (Engineered Stomach and Small Intestine) system developed by MEDIS, to integrate the gut microbiota in the small intestinal compartments and to pursue improvements allowing digestion of real-size food particles. The two latter parameters could widely influence the digestibility of lipids/carbohydrates and the bioaccessibility of active compounds. These research activities will enable to develop before 2024 the most complete system worldwide simulating the human upper digestive tract and to validate this model according to clinical data obtained by Valbiotis. The MIMETiv project will provide tremendous knowledge’s for the company related to the fate of TOTUM products in the simulated human digestive environment (bioaccessibility, metabolism by gut microbiota) and obtain relevant data on their mode of action, such as their ability to modify the digestion or intestinal absorption of lipids/carbohydrates, limit intestinal microbiota dysbiosis or modulate hepatic metabolic pathways (through original coupling of ESIN with hepatic cells in culture). MIMETiv will enable for MEDIS significant scientific output (publications, in vitro digestion leadership) and economic benefits since a patent related to ESIN is planned and the optimized model will strengthen the various platforms associated to the lab, i.e. UCA partner DIGEST'iv (local), IRICE PRIMUM (regional) and CALIS (national). It will also reinforce the possibility of creating a service company. In addition, Valbiotis plans to commercialize its products within 2 to 4 years worldwide, with employment and financial spinoffs for the company, but also for UCA, co-owner of the patents. This project will be perpetuated by extending research to other products from the company actually under development and by broadening the potential of ESIN to other pathologies associated to gut microbiota perturbations (eg diabetes, obesity).

Project coordination

Stéphanie BLANQUET-DIOT (Microbiologie, Environnement Digestif et Santé)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

VALBIOTIS VALBIOTIS
MEDIS Microbiologie, Environnement Digestif et Santé

Help of the ANR 363,000 euros
Beginning and duration of the scientific project: December 2022 - 54 Months

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