Endocrine Abstracts

JOINT1689

The stigmas of Crocus sativus (Cr), known as saffron spice, are recognized as a dietary supplement for the treatment of obesity and type 2 diabetes due to their potent antidiabetic, hypolipidemic and antioxidant potential. Recently, the bioactive components of Cr tepals, which are wasted during saffron production, have also been shown to have significant hypoglycemic properties. The use of dietary supplements of herbal origin could affect the composition of the gut microbiota, which influences host energy homeostasis and in the long run affects the prevalence of obesity and related metabolic complications. Therefore, we investigated whether the gut microbiota could play a mediating role in the beneficial effect of Cr tepals extract on systemic glucose tolerance in an animal model of diet-induced obesity. Male C57BL/6J mice were fed a standard diet (10 kcal% fat) or a high-fat diet (60 kcal% fat) for 14 weeks. Mice on the high-fat diet were treated orally with Cr tepals extract for the last 5 weeks of the diet. Biochemical and physiological parameters and an intraperitoneal glucose tolerance test were performed to estimate systemic glucose tolerance. The composition and diversity of gut microbiota was analyzed by 16S rRNA sequencing of bacterial DNA isolated from fecal samples. Gut integrity was assessed by measuring the level of fluorescently labeled (FITC) dextran in blood and by quantifying the level of tight junction proteins by Western blot. Oral administration of Cr tepals extract reduced body mass of obese animals and lowered glucose and insulin levels, as well as the HOMA index, indicating an improvement in systemic glucose tolerance. Greater richness and evenness of the gut microbiota were confirmed by a lower Firmicutes/Bacteroidetes ratio and increased alpha diversity indices. The composition of the gut microbiota shifted towards an increased abundance of the genera Odoribacter, Alistipes, Candidatus Saccharimonas and Intestinimonas, which are negatively correlated with insulin resistance and inflammation. The level of FITC-dextran was reduced and the expression of Zonula occludens 1 protein was increased, which led to an improvement of intestinal integrity. Cr tepals extract has a positive effect on gut microbiota composition, compromised by a high-fat diet, by increasing the abundance of bacterial genera that can be associated with the amelioration of glucose tolerance. This beneficial effect could be the result of improved gut integrity and reduced permeability. Our results highlight Cr tepals extract as an effective natural supplement for the treatment of obesity-related metabolic disorders without side effects.