Angiotensin-(1-7) modulates gut-bone marrow axis in diabetes.

Area of Science:

• Endocrinology
• Gastroenterology
• Immunology

Background:

• Diabetes mellitus is associated with compromised colon epithelial barrier integrity and heightened inflammation.
• Myelopoiesis in the bone marrow is dysregulated in diabetes, contributing to systemic inflammation.
• Angiotensin-(1-7) (Ang-(1-7)) is a peptide with known cardiovascular protective effects in diabetes.

Purpose of the Study:

• To investigate if Ang-(1-7) can restore colon epithelial barrier integrity and normalize myelopoiesis in diabetic mice.
• To determine if Ang-(1-7) ameliorates diabetes-induced gut dysbiosis and bone marrow inflammatory landscape.

Main Methods:

• Streptozotocin-induced type 1 and db/db type 2 diabetic mouse models were treated with Ang-(1-7).
• Intestinal permeability was assessed using FITC-dextran assay.
• Colon epithelial barrier markers, intestinal stem cells (ISCs), gut microbiota composition, and bone marrow inflammatory profiles were analyzed.

Main Results:

• Ang-(1-7) significantly reversed increased intestinal permeability in both diabetic models.
• The peptide restored Wnt3a and β-catenin levels in the colon and reduced pro-inflammatory monocytes and macrophages in the bone marrow.
• Ang-(1-7) modulated gut microbiota composition, increasing beneficial bacteria and decreasing plasma levels of trimethylamine N-oxide (TMAO) and lipopolysaccharide-binding protein (LBP).

Conclusions:

• Angiotensin-(1-7) demonstrates significant potential in ameliorating diabetic disruptions of colon barrier integrity and inflammation.
• The peptide achieves these effects by restoring regenerative intestinal stem cells and reversing aberrant myelopoiesis.
• Ang-(1-7) offers a promising therapeutic strategy for managing diabetic gastrointestinal complications and systemic inflammation.