Oral Angiotensin-(1-7) Peptide Modulates Intestinal Microbiota Improving Metabolic Profile in Obese Mice

Abstract

Background: Obesity is a serious health problem that dysregulate Renin-Angiotensin System (RAS) and intestinal microbiota.

Objective: The present study aimed to evaluate the Angiotensin-(1-7) [ANG-(1-7)] oral formulation effects on obese mice intestinal microbiota.

Methods: Mice were divided into four groups: obese and non-obese treated with ANG-(1-7) and obese and non-obese without ANG-(1-7) during four weeks.

Results: We observed a significant decrease in the fasting plasma glucose, total cholesterol, triglycerides, and Low-density lipoprotein levels and increased High-density lipoprotein in animals treated with ANG-(1-7). The histological analysis showed intestinal villi height reduction in mice treated with ANG-(1-7). Additionally, increased Bacteroidetes and decreased Firmicutes (increased Bacteroidetes/ Firmicutes ratio) and Enterobacter cloacae populations were observed in the High-Fat Diet + ANG-(1-7) group. Receptor toll-like 4 (TLR4) intestinal mRNA expression was reduced in the HFD+ANG-(1-7) group. Finally, the intestinal expression of the neutral amino acid transporter (B0AT1) was increased in animals treated with ANG-(1-7), indicating a possible mechanism associated with tryptophan uptake.

Conclusion: The results of the present study suggest for the first time an interaction between oral ANG-(1-7) and intestinal microbiota modulation.

Keywords: ACE2.; Gut microbiota; metabolic endotoxemia; metabolism; renin-angiotensin system; small intestine.