Effects of angiotensin (1–7) producing Lactobacillus paracasei and palmitoleic acid on angiotensin converting enzyme 2 (ACE2) expression and gut microbiota in streptozotocin-induced diabetic rats

Diabetes mellitus is a metabolic disease characterized by hyperglycemia due to defects in insulin secretion or action. This study aimed to investigate the effects of angiotensin (1–7) producing Lactobacillus paracasei (LP) and palmitoleic acid (PA) on ACE2 expression and gut microbiota in a streptozotocin (STZ)-induced diabetic rat model. A total of 42 male Wistar rats were divided into 7 groups: Control, STZ, LP, PA, STZ, STZ + LP, STZ + PA and STZ + LP+PA. Blood glucose level, ACE2 expression level by Western blot analysis, microbiota analysis and histopathologic examination were performed between the groups. Blood glucose levels were significantly elevated in STZ (60 mg/kg) treated groups (428.67 ± 18.44 vs. control 76.00 ± 4.52), whereas the combination of LP and PA brought blood glucose levels closer to control (103.00 ± 7.48). In Western blot analysis, ACE2 expression decreased in the STZ group, whereas LP and PA treatments increased this expression. The most significant increase was observed in the STZ + LP+PA group. Microbiota analysis showed that LP and PA increased intestinal diversity (Shannon index: 4.774) and decreased pathogenic species. Histopathologic examinations revealed severe degeneration and Nuclear Factor Kappa B (NF-κB) expression in the liver, intestine, and spleen in the STZ group, whereas the combination treatment attenuated this damage. In immunofluorescence analysis, Caspase-3 and Toll-Like Receptor 4 (TLR4) expression was significantly reduced in the STZ + LP+PA group. LP and PA has therapeutic potential in reducing diabetes-induced microbiota dysbiosis and inflammation by regulating the ACE2 pathway.