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

2025-02-19
Microorganisms 13(2)

PubMed: 40005829
DOI: 10.3390/microorganisms13020464

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

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Akkermansia muciniphila WB-STR-0001	—	Reduced Intestinal Inflammation	Beneficial	Moderate	View source 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
Akkermansia muciniphila WB-STR-0001	—	Reduced Oxidative Stress	Beneficial	Moderate	View source 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)