Moez Rhimi

Insects rely on carbohydrates such as starch and glycogen as an energy supply for growth of larvae and for longevity. In this sense α-amylases have essential roles under extreme conditions, e.g., during nutritional or temperature stress, thereby contributing to survival of the insect. This makes them interesting targets for combating insect pests. Drosophila melanogaster α-amylase, DMA, which belongs to the glycoside hydrolase family 13, sub family 15, has been studied from an evolutionary, biochemical, and structural point of view. Our studies revealed that the DMA enzyme is active over a broad temperature and pH range, which is in agreement with the fluctuating environmental changes with which the insect is confronted. Crystal structures disclosed a new nearly fully solvated metal ion, only coordinated to the protein via Gln263. This residue is only conserved in the subgroup of D. melanogaster and may thus contribute to the enzyme adaptive response to large temperature variations. Studies of the effect of plant inhibitors and the pseudo-tetrasaccharide inhibitor acarbose on DMA activity, allowed us to underline the important role of the so-called flexible loop on activity/inhibition, but also to suggest that the inhibition modes of the wheat inhibitors WI-1 and WI-3 on DMA, are likely different.

The gut microbiota is now considered as a key player in the development of metabolic dysfunction. Therefore, targeting gut microbiota dysbiosis has emerged as a new therapeutic strategy, notably through the use of live gut microbiota-derived biotherapeutics. We previously highlighted the anti-inflammatory abilities of two Parabacteroides distasonis strains. We herein evaluate their potential anti-obesity abilities and show that the two strains induced the secretion of the incretin glucagon-like peptide 1 in vitro and limited weight gain and adiposity in obese mice. These beneficial effects are associated with reduced inflammation in adipose tissue and the improvement of lipid and bile acid metabolism markers. P. distasonis supplementation also modified the Actinomycetota, Bacillota and Bacteroidota taxa of the mice gut microbiota. These results provide better insight into the capacity of P. distasonis to positively influence host metabolism and to be used as novel source of live biotherapeutics in the treatment and prevention of metabolic-related diseases.