A sponsorship from Quercia Venture Management in support of obesity research

An innovative research program on the theme of "Nutrition and Obesity: Systemic Approaches", led by Professor Karine Clément and her team, benefits from the sponsorship of Quercia Venture Management.
We are currently experiencing a global epidemic of obesity resulting from the interactions between our genetic heritage and numerous environmental factors. Even if progress has been made in the evolution of treatments, current hygienic and dietary approaches do not allow for an effective and sustainable treatment of all forms of obesity and their associated complications (type 2 diabetes: T2DM, cardiovascular diseases, dyslipidemia, etc.). Moreover, although bariatric surgery is the most effective approach to treat individuals suffering from severe obesity, this procedure remains cumbersome and is reserved for the most severe patients. It is estimated that 20% of the world's adults will be obese by 2030 and more than 511 million will have T2DM. New therapeutic targets and treatments need to be developed to improve the therapeutic management of patients, prevent the development and progression of obesity and prevent the onset of complications. The challenge is therefore global and it is important to develop new therapeutic solutions.

The intestinal microbiota (IM), i.e. the 100,000 billion microorganisms (viruses, bacteria, archaea, fungi) that colonize the digestive tract, constitutes one of the promising therapeutic targets since it was identified, about twenty years ago, as a new actor involved in the pathophysiology of obesity and associated metabolic disorders.
The NutriOmics laboratory (UMRS 1269) of Prof. Karine Clément is specifically interested in the study of a new generation bacterium close to the Sutterellaceae family, to define if it can have a beneficial role in metabolic health and type 2 diabetes.
Indeed, converging results from microbiota analysis by sequencing and quantitative PCR in several projects, allow the recurrent observation of a positive association between the abundance of a bacterial species of the Sutterellaceae family in the fecal microbiota and metabolic health (lower weight and better glucose tolerance). This species was isolated in 2017 from the caecal contents of mice. In particular, it was shown that the proportion of obese subjects with detectable levels of this species (20%) was significantly lower than that observed with individuals of normal build (35%). Furthermore, in an obese population, this species was detected exclusively in patients with normal fasting blood glucose levels, i.e., less than 1.1 g/L. In mice, its abundance also appears to be associated with better metabolic health as it is increased by bariatric surgery as well as by prebiotic supplementation. The identification of these associations, however, required the evaluation of the causal effects of this bacterium on the metabolic phenotype of rodents.
During 2021/2022, the team was able to demonstrate that this bacterium was more abundant in the small intestine and in particular in the ileal contents of mice on a control diet. In rodents, the team also showed that its abundance was strongly decreased by a hyper-lipidic diet, showing the impact of the diet on the abundance of this bacterium. The positive associations between the abundance of this species of the Sutterellaceae and a healthy metabolic status in humans and mice suggest a beneficial impact of this bacterium on the health of the host without, however, really demonstrating it.
Thus, the team sought to confirm or refute the causal role of this bacterium of interest on the metabolic health of mice. In a first study, the team finally showed that this bacterium acted favorably on body composition and carbohydrate metabolism without affecting food intake, transit time or the quantity of calories absorbed from food.
The research program, which Quercia Venture Management is generously supporting, will take place over 3 years and aims to :
1. Confirm: (a) the results of the preliminary studies by increasing the size of the human cohorts and by studying the associations between the abundance of this bacterium, diet and drug intake, and (b) the initial data obtained by repeating the experiment in a mouse model and by carrying out complementary metabolic tests.
2. Highlight the mechanisms of action by which this bacterium impacts mouse physiology by: (a) identifying which metabolic pathways are modulated by this bacterium, and (b) determining how and by which effectors this bacterium modulates these metabolic pathways.
Promising results could eventually lead to the development of a new probiotic and/or postbiotic, aimed at limiting body weight gain and alteration of carbohydrate metabolism in overweight or obese individuals.

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Professeur Karine Clément – NutriOmique Research group - Sorbonne Université-Inserm
Florence Mahé-Dombis - Director of the health sponsorship - Fondationof Sorbonne University