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Characterization and Anti-Inflammatory Effects of Akkermansia muciniphila-Derived Extracellular Vesicles.

  • 2025-02-19
  • Microorganisms 13(2)
    • Sasa Zhao
    • Jie Xiang
    • Minhazul Abedin
    • Jingyi Wang
    • Zhiwen Zhang
    • Zhongwei Zhang
    • Hua Wu
    • Junsong Xiao

Study Design

Population
human colorectal adenocarcinoma cells (Caco-2)
Methods
In vitro model of lipopolysaccharide (LPS)-induced inflammation; treatment with 25 and 50 μg/mL Am-EVs isolated from Akkermansia muciniphila using ultracentrifugation
Bacterial extracellular vesicles (EVs) play a pivotal role in host-microbe communication. Akkermansia muciniphila, a symbiotic bacterium essential for intestinal health, is hypothesized to exert its effects via EVs. Here, we successfully isolated and characterized EVs derived from A. muciniphila (Am-EVs) using ultracentrifugation. Am-EVs exhibited a double-membrane structure, with an average diameter of 92.48 ± 0.28 nm and a proteomic profile comprising 850 proteins. In an in vitro model of lipopolysaccharide (LPS)-induced inflammation in human colorectal adenocarcinoma cells (Caco-2), treatment with both 25 and 50 μg/mL Am-EVs significantly reduced oxidative stress markers, including reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA), while restoring catalase activity (CAT). Am-EVs also suppressed the expression of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). Subsequent transcriptomic sequencing and Western blot experiments revealed that Am-EVs attenuate the MAPK signaling pathway by downregulating TRIF, MyD88, p38 MAPK, and FOS while upregulating TGFBR2. These findings suggest that Am-EVs mediate anti-inflammatory effects through modulation of MAPK signaling, highlighting their potential as therapeutic agents in intestinal inflammation.

Research Insights

  • Akkermansia muciniphila WB-STR-0001→Reduced Intestinal Inflammation

    Am-EVs also suppressed the expression of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6)... These findings suggest that Am-EVs mediate anti-inflammatory effects through modulation of MAPK signaling

    Effect
    Beneficial
    Effect size
    Moderate
  • Akkermansia muciniphila WB-STR-0001→Reduced Oxidative Stress

    treatment with both 25 and 50 μg/mL Am-EVs significantly reduced oxidative stress markers, including reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA), while restoring catalase activity (CAT)

    Effect
    Beneficial
    Effect size
    Moderate
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