Exploring the role of dietary γ-glutamyl valine (γ-EV) in modulating the gut microbiota to mitigate high-fat diet-induced atherosclerosis

Tuesday, April 29, 2025

5:00 PM – 6:00 PM PST

Room: Expo Hall

Presenting Author(s)

Sedoten O. Ogun, MS

Graduate Research Assistant
University of Nebraska Lincoln
Lincoln, NE, United States

Co-Author(s)

AR

Amanda Ramer-Tait

Professor
University of Nebraska-Lincoln
Lincoln, Nebraska, United States
Kaustav Majumder, PhD (he/him/his)

Associate Professor
University of Nebraska-Lincoln
Lincoln, NE, United States

Abstract: Atherosclerosis, marked by plaque buildup and lipid deposition in arteries, is a significant contributor to cardiovascular diseases, the leading cause of global morbidity and mortality. Current treatments primarily focus on addressing the aftermath of atherosclerosis, such as plaque rupture, thrombosis, or heart attacks. However, there are limited preventive strategies available to target the underlying progression of the disease. γ-glutamyl valine (γ-EV), a bioactive peptide predominantly found in fermented foods, has promising anti-atherosclerotic properties. However, only a portion—76%—of this peptide is bioavailable. Thus, we hypothesized that the 24% non-bioavailable γ-EV may modulate the gut microbiome, bringing about the prevention of atherosclerosis. Atherosclerosis-prone APO E-/- mice were fed either a Low-Fat Diet (LFD; 10% kcal fat), a High-Fat Diet (HFD; 40% kcal fat), or a HFD supplemented with 150 mg/kg γ-EV for 15 weeks. Treatment with γ-EV significantly reduced the lipid accumulation in the aortas of HFD-fed APO E-/- mice compared to mice receiving HFD alone. 16S rRNA bacterial gene sequencing analysis of the microbiome revealed that γ-EV treatment increased Akkermansia compared to HFD feeding, and qPCR testing identified that γ-EV particularly enriched for Akkermansia muciniphila, a beneficial gut bacterium. Correlation analyses revealed a strong, negative association between Akkermansia abundance and reduced lipid deposition and inflammation. Previous studies have shown that A. muciniphila limits chronic inflammation and protects against atherosclerosis. We therefore tested if treatment with γ-EV could directly influence the abundance of A. muciniphila in vitro. Treatment with 5 mM and 10 mM doses of γ-EV both significantly enhanced the growth of A. muciniphila compared to control media. Altogether, the findings from this study suggest that γ-EV may limit the development of atherosclerosis by promoting the growth of A. muciniphila. Future studies will investigate the requirement of A. muciniphila in vivo for mediating the anti-atherosclerotic properties of γ-EV.