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Akkermansia muciniphila and Its Extracellular Vesicles Affect Endocannabinoid System in in vitro Model
Pegah Noori1, Fattah Sotoodehnejadnematalahi1, Pooneh Rahimi2
1Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Introduction:
Recent studies indicate that the gut microbiota controls the host's immune system. Probiotics use different signaling pathways to regulate intestinal permeability, barrier integrity, and energy balance.
Methods:
This research examined how Akkermansia muciniphila and its extracellular vesicles (EVs) impact inflammation and genes related to the endocannabinoid system in the STC-1 cell line through RT-PCR and ELISA assays.
Results:
The study's results indicated that EVs had a significant impact on GLP-1 expression compared to the multiplicity of infections (MOI) ratio. Notably, there was a substantial increase in the expression of PYY and GLP-1 genes across all treatments (p < 0.05). Conversely, the expression of CB-1, CB-2, and FAAH genes notably decreased in the STC-1 cell line when treated with MOI 50 of A. muciniphila and an EV concentration of 100 μg/mL (p < 0.05). Both MOI 50 of A. muciniphila and an EV concentration of 100 μg/mL significantly enhanced the expression of the TLR-2 gene. In contrast, EVs at a concentration of 100 μg/mL substantially reduced TLR-4 gene expression. A. muciniphila-derived EVs notably decreased the levels of inflammatory cytokines (TNF-α and IL-6), while increasing IL-10 expression at MOI 100 and an EV concentration of 100 μg/mL. These findings suggest that A. muciniphila and its EVs could regulate the expression of specific genes, serving as targets for maintaining host energy balance.
Conclusions:
In summary, this study illustrates that A. muciniphila-derived EVs exhibit anti-inflammatory properties and have the potential to modulate gene expression in cases of obesity and gastrointestinal tract inflammation.
Insights
Akkermansia muciniphila extracellular vesicles (EVs) demonstrate anti-inflammatory effects by modulating gut gene expression. These probiotics show potential for managing obesity and gastrointestinal inflammation.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Gut microbiota significantly influences host immune system regulation.
- Probiotics impact intestinal permeability, barrier integrity, and energy balance via signaling pathways.
Purpose of the Study:
- To investigate the effects of Akkermansia muciniphila and its extracellular vesicles (EVs) on inflammation and endocannabinoid system genes.
- To analyze gene expression changes in the STC-1 cell line using RT-PCR and ELISA.
Main Methods:
- Treatment of STC-1 cells with A. muciniphila at various multiplicities of infection (MOI) and EVs at specific concentrations.
- Gene expression analysis using RT-PCR and ELISA assays.
- Quantification of inflammatory cytokines and gene markers.
Main Results:
- A. muciniphila EVs significantly impacted GLP-1 expression and increased PYY and GLP-1 gene expression.
- Decreased expression of CB-1, CB-2, and FAAH genes observed with A. muciniphila and EVs.
- Enhanced TLR-2 and reduced TLR-4 gene expression, with decreased TNF-α and IL-6, and increased IL-10 by A. muciniphila EVs.
Conclusions:
- A. muciniphila-derived EVs possess anti-inflammatory properties.
- EVs modulate gene expression related to energy balance and inflammation.
- Potential therapeutic applications for obesity and gastrointestinal inflammation.

