Sustained ACE2 Expression by Probiotic Improves Integrity of Intestinal Lymphatics and Retinopathy in Type 1 Diabetic...

Area of Science:

• Gastroenterology
• Ophthalmology
• Endocrinology

Background:

• Intestinal lacteals are crucial for gut homeostasis, lipid absorption, and immune function.
• Type 1 diabetes (T1D) impacts gut barrier integrity and is linked to diabetic retinopathy.
• Previous work showed diabetes reduces intestinal angiotensin-converting enzyme 2 (ACE2), disrupting the gut barrier.

Purpose of the Study:

• To investigate the effect of T1D on intestinal lymphatics and circulating lipids.
• To evaluate the therapeutic potential of ACE2-expressing probiotics (LP-ACE2) on gut and retinal function in a T1D mouse model.

Main Methods:

• Utilized Akita mice with T1D, treated with LP-ACE2 (Lactobacillus paracasei engineered to express human ACE2).
• Assessed intestinal lymphatic and barrier integrity via immunohistochemistry (LYVE-1, ZO-1, p120-catenin, PLVAP1).
• Evaluated retinal function (visual acuity, electroretinograms) and vascular changes (acellular capillaries, BRB markers ZO-1, VCAM-1).

Main Results:

• LP-ACE2 treatment significantly restored intestinal lacteal integrity (increased LYVE-1) and improved gut epithelial/endothelial barrier function (ZO-1, p120-catenin, PLVAP1).
• Treatment reduced plasma LDL cholesterol and enhanced lipid transport in retinal pigment epithelial cells (increased ABCG1).
• LP-ACE2 corrected blood-retinal barrier dysfunction (increased ZO-1, decreased VCAM-1) and decreased retinal acellular capillaries.

Conclusions:

• LP-ACE2 effectively restores intestinal lacteal integrity and gut barrier function in T1D.
• This probiotic intervention improves systemic lipid metabolism and ameliorates diabetic retinopathy severity.
• Targeting the gut-retinal axis via ACE2 modulation holds promise for managing diabetic complications.