A novel protein B2URF3 from Akkermansia muciniphila increased by intermittent fasting alleviates vascular calcification - Research article abstract

Sep 30, 2026

Uploaded by Franzy

Vascular calcification (VC) drives cardiovascular morbidity and mortality, yet lacks effective therapies. Alternate-day intermittent fasting (IF1:1) attenuates vitamin D–induced VC in mice, while a 5:2 regimen is ineffective. The benefit depends on gut microbiota, with Akkermansia muciniphila enrichment. Microbiota-derived extracellular vesicles act as nano-scale mediators that deliver signals to vascular smooth muscle cells, suppressing osteogenic differentiation and calcification. Proteomics identify B2URF3 as a functional protein in Akk-EVs, interacting with ALDH1B1 to inhibit osteogenic transdifferentiation; human data show reduced fecal Akk and lower serum B2URF3 in coronary calcification patients, supporting a gut-vascular axis and candidate targets.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Abstract

Keywords

Introduction

Vascular calcification and need for therapies

Intermittent fasting and reported metabolic effects

Rationale for gut microbiota and extracellular vesicles

Zeng et al. Journal of Nanobiotechnology (2026) 24:21 [https://doi.org/10.1186/s12951-025-03948-0](https://doi.org/10.1186/s12951-025-03948-0) Journal of Nanobiotechnology RESEARCH Open Access A novel protein B2URF3 from Akkermansia muciniphila increased by intermittent fasting alleviates vascular calcification Shi-Yu Zeng1,2, Jiang-Hua Liu6, Ying-Ying Xiang1, Zhao-Lin Zeng1,9, Zhi-Bo Zhao 1, Jie zheng 1, Yi-Fu Liu8, Zhi-Rou Lin 1, Yi-Yi Wang3,4, Chun-Gu Hong3,4, Ling Jin3,4, Guo-Qiang Zhu3,4, Yi-Wei Liu3,4, Xin Wang3,4, Xiao-Xue Li3,4, Zhe Guan3,4, Zhen-Xing Wang3,4, Ting Sun10, Hui Xie3,4,5* and Jiang-Hua Liu 1,7* Abstract Vascular calcification (VC) is a major contributor to cardiovascular morbidity and mortality, yet effective therapies are lacking. Here, we show that alternate-day intermittent fasting (IF1:1) attenuates vitamin D-induced VC in mice, whereas a 5:2 regimen is ineffective. The protective effect of IF1:1 is gut microbiota-dependent, particularly through enrichment of Akkermansia muciniphila (Akk) . Microbiota-derived extracellular vesicles (EVs) function as nano-scale mediators that bypass the spatiotemporal constraints of bacterial survival to facilitate long-distance communication with host cells, providing a crucial pathway for downstream mechanistic investigation. Akk-derived EVs (Akk-EVs) are internalized by vascular smooth muscle cells (VSMCs), suppressing osteogenic differentiation and calcification in vitro and in vivo. Proteomic analysis identified B2URF3 as a highly enriched functional protein in Akk-EVs and Akk, which interacts with Aldehyde Dehydrogenase 1 Family Member B1 (ALDH1B1) to inhibit VSMC osteogenic transdifferentiation. Clinically, reduced fecal Akk abundance and lower serum B2URF3 levels were observed inpatients with coronary calcification. These findings define a gut-vascular axis by which IF1:1 mitigates VC and nominate Akk-EVs and B2URF3 as potential therapeutic targets and biomarkers. Keywords Intermittent fasting, Gut-vascular axis, Akkermansia muciniphila, Extracellular vesicles, Vascular calcification Introduction Vascular calcification (VC) is a pathological process characterized by the deposition of calcium phosphate crystals in the arterial wall, which is strongly associated with increased risk of cardiovascular disease [1]. Therefore, developing effective therapeutic strategies to prevent or *Correspondence: Hui Xie [huixie@csu.edu.cn](huixie@csu.edu.cn)[ ](huixie@csu.edu.cn)Jiang-Hua Liu [liujianghua@usc.edu.cn](liujianghua@usc.edu.cn) Full list of author information is available at the end of the article treat this condition is of great importance. Intermittent fasting (IF), an emerging dietary strategy that involves cycling between periods of fasting and non-fasting including alternate day fasting (IF1:1) and 5:2 intermittent fasting (IF5:2) [2], has gained considerable attention in recent years due to its potential effects on metabolism, inflammation and cardiovascular health [3, 4]. Several studies have reported beneficial effects of IF on weight loss [4], insulin sensitivity [5], lipid profile [6], and blood pressure [7], as well as a reduction in markers of inflammation and oxidative stress [8]. However, whether IF can protect aorta from calcification remains to be elucidated. © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutor

FAQs

How does alternate-day intermittent fasting affect vitamin D–induced vascular calcification in mice?

Alternate-day intermittent fasting (IF1:1) attenuates vitamin D–induced vascular calcification in mice.

Why is the protective effect of IF1:1 linked to gut microbiota?

The protective effect is gut microbiota-dependent, particularly through enrichment of Akkermansia muciniphila.

What role do Akkermansia-derived extracellular vesicles and B2URF3 play?

Akk-derived extracellular vesicles are internalized by vascular smooth muscle cells, suppressing osteogenic differentiation and calcification. Proteomic analysis identifies B2URF3 as a functional protein that interacts with ALDH1B1 to inhibit osteogenic transdifferentiation.

Sep 30, 2026

Uploaded by Franzy