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A novel protein B2URF3 from Akkermansia muciniphila increased by intermittent fasting alleviates vascular

Shi-Yu Zeng1,2, Jiang-Hua Liu3, Ying-Ying Xiang1

  • 1Department of Metabolism and Endocrinology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.

Journal of Nanobiotechnology
|January 8, 2026
PubMed

Insights

Alternate-day intermittent fasting (IF1:1) reduces vascular calcification in mice by enhancing gut bacteria, particularly Akkermansia muciniphila. This effect involves Akk-derived extracellular vesicles carrying the protein B2URF3, offering potential therapeutic targets.

Area of Science:

  • Cardiovascular Research
  • Microbiome Science
  • Metabolic Disease

Background:

  • Vascular calcification (VC) significantly increases cardiovascular disease risk, with limited effective treatments.
  • The gut microbiome's role in systemic health, including vascular function, is increasingly recognized.

Purpose of the Study:

  • To investigate the efficacy of intermittent fasting (IF) regimens in preventing vitamin D-induced VC.
  • To elucidate the role of gut microbiota and their derived extracellular vesicles (EVs) in mediating the protective effects of IF against VC.
  • To identify specific molecular mechanisms and potential biomarkers involved in the gut-vascular axis.

Main Methods:

  • Utilized a mouse model of vitamin D-induced VC to compare alternate-day (IF1:1) and 5:2 IF regimens.
  • Assessed the impact of IF on gut microbiota composition, focusing on Akkermansia muciniphila (Akk).
  • Investigated the function of Akk-derived EVs (Akk-EVs) in vascular smooth muscle cells (VSMCs) in vitro and in vivo.
  • Performed proteomic analysis to identify key proteins within Akk-EVs and Akk, and validated interactions with host proteins.
  • Analyzed fecal and serum samples from patients with coronary calcification to correlate findings with clinical observations.

Main Results:

  • Alternate-day intermittent fasting (IF1:1) significantly attenuated vitamin D-induced VC in mice, while a 5:2 IF regimen was ineffective.
  • The protective effect of IF1:1 was dependent on gut microbiota, specifically an enrichment of Akkermansia muciniphila (Akk).
  • Akk-EVs were internalized by VSMCs, suppressing osteogenic differentiation and calcification.
  • The protein B2URF3, highly abundant in Akk-EVs and Akk, was identified as a key mediator, interacting with ALDH1B1 to inhibit VSMC osteogenic transdifferentiation.
  • Reduced fecal Akk abundance and lower serum B2URF3 levels were observed in patients with coronary calcification.

Conclusions:

  • Alternate-day intermittent fasting establishes a gut-vascular axis that mitigates vascular calcification.
  • Akkermansia muciniphila and its derived extracellular vesicles (Akk-EVs) play a crucial role in this protective mechanism.
  • The Akk-EV protein B2URF3 is a critical mediator inhibiting VSMC osteogenic differentiation and represents a potential therapeutic target and biomarker for vascular calcification.
Keywords:
Akkermansia muciniphilaExtracellular vesiclesGut-vascular axisIntermittent fastingVascular calcification

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