Intestinal Bacterium Akkermansia muciniphila Inhibits Progression of Abdominal Aortic Aneurysm

Area of Science:

• Vascular Biology
• Microbiome Research
• Molecular Medicine

Background:

• Abdominal aortic aneurysm (AAA) is a life-threatening condition with limited treatment options.
• The role of the gut microbiome, specifically Akkermansia muciniphila (Akk), in AAA pathogenesis is not fully understood.
• Investigating molecular mechanisms is crucial for developing novel therapeutic strategies.

Purpose of the Study:

• To elucidate the molecular mechanisms by which Akkermansia muciniphila (Akk) exerts therapeutic effects in abdominal aortic aneurysm (AAA).
• To explore the interplay between Akk, neutrophil extracellular traps (NETs), high mobility group box 1 (HMGB1), and ferroptosis in VSMCs.
• To identify key signaling pathways, such as AMPK, involved in Akk's protective effects against AAA.

Main Methods:

• 16S rRNA sequencing to analyze gut microbial composition.
• Transcriptome sequencing to identify molecular changes in response to Akk treatment.
• In vivo AAA models and in vitro cell studies using vascular smooth muscle cells (VSMCs).
• Assessment of extracellular matrix degradation, NET formation, and ferroptosis.

Main Results:

• Akk treatment significantly reduced AAA development and extracellular matrix degradation.
• Akk suppressed HMGB1-induced NET formation, a key driver of AAA progression.
• Akk activated AMP-activated protein kinase (AMPK) to inhibit VSMC ferroptosis, a form of cell death implicated in AAA.
• HMGB1 exacerbated ferroptosis, while Akk's activation of AMPK reversed this effect.

Conclusions:

• Akkermansia muciniphila (Akk) mitigates AAA progression by inhibiting HMGB1-mediated NET formation and reducing VSMC ferroptosis via AMPK activation.
• These findings highlight a novel therapeutic pathway involving the gut microbiome and cellular metabolism in AAA.
• Akk represents a promising candidate for the development of innovative therapies for abdominal aortic aneurysm.