Camel milk and fermented camel milk attenuate HFD/STZ-induced type 2 diabetes in rats via modulation of gut microbiota-SCFA-GLP-1/PI3K/AKT axis

Abstract

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder defined by chronic hyperglycemia and a propensity for severe complications. While camel milk (CM) and fermented camel milk (FCM) have been proposed as potential interventions, the mechanistic evidence explaining how they ameliorate T2DM symptomatology remains limited. Our findings demonstrate that administration of CM and FCM significantly attenuated hallmark metrics of T2DM in a rat model, including decreases in fasting blood glucose to 79.6% and 70.8% of the model group levels, respectively [ p < 0.01], the homeostatic model assessment of insulin resistance [ p < 0.01], levels of pro-inflammatory cytokines. Analysis of the gut microbiota revealed that CM and FCM restored intestinal homeostasis. This was evidenced by a decreased Firmicutes/Bacteroidetes ratio and an increased relative abundance of beneficial taxa. Notably, FCM intervention uniquely and markedly enriched the abundance of intestinal Akkermansia, Blautia , Clostridia UCG-014 and Ruminococcus . Correlation analysis identified Clostridia UCG-014 and Ruminococcus as key microbial contributors to the observed amelioration of glucose and lipid metabolic disorders, the elevated short-chain fatty acids levels, and the activation of the glucagon-like peptide 1/phosphatidylinositol-3-kinase/protein kinase B (GLP-1/PI3K/AKT) signaling pathway. Comparatively, FCM intervention conferred a more pronounced therapeutic benefit on T2DM than CM. In conclusion, we elucidate the key role and differential effects of the intestinal GLP-1/PI3K/AKT signaling pathway in mediating the improvement of glycemic homeostasis and insulin sensitivity following CM and FCM intervention. These findings substantiate the potential of both, particularly FCM, as viable dietary interventions for the clinical management of T2DM.