Related Experiment Video
Updated: Apr 18, 2026
Intracerebroventricular Delivery of Gut-Derived Microbial Metabolites in Freely Moving Mice
Published on: June 2, 2022
Akkermansia muciniphila improving depression-like behaviors by regulating glycerophospholipid metabolism in gut-brain
Fei He1, Shunjie Bai2, Jing Xie3
1Institute of Neuroscience, School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.
Background:
Akkermansia muciniphila (AKK) is a potential probiotic. Our previous studies have shown that it could alleviate depressive-like behaviors (DLBs) in mice by inhibiting neuroinflammation in brain. To further explore its antidepressant effect, this study focused on the effects of AKK on the metabolic activities in gut-brain axis.
Methods:
After chronic restraint stress (CRS) depression model was successfully built, AKK was used as intervention method for 3 weeks. The gut microbiome in feces and two intestinal permeability proteins in colon (Claudin-1, Occludin) were measured, and the metabolites in feces, colon, liver, and prefrontal cortex were also measured. In addition, two inflammation-related factors in hippocampus (Free fatty acid receptors 3 (FFAR3), phosphorylated NF-κB p65 (p-p65)) were measured.
Results:
AKK was successfully colonized in gut of chronic restraint stress (CRS) mice. The DLBs in CRS mice receiving AKK (CRS + AKK) were significantly improved, along with the improved gut microbiome. Both Claudin-1 and Occludin in colon were significantly increased in CRS + AKK mice compared to CRS mice receiving phosphate buffer saline (PBS) (CRS + p). Metabolomics analysis indicated that AKK could significantly improve the changed lipids and lipid-like molecules in gut-brain axis of CRS mice; and function analysis using differential metabolites showed that AKK could significantly improve the disordered glycerophospholipid metabolism in feces, colon, liver, and prefrontal cortex of CRS mice. Additionally, we found that FFAR3 and phosphorylated NF-κB p65 were increased and decreased, respectively, in hippocampus of CRS + AKK mice compared to CRS + p mice.
Conclusion:
Our results suggested that AKK might improve the disturbances of gut microbiome, intestinal permeability, host's lipid metabolism and inflammation levels in hippocampus. Glycerophospholipid metabolism in gut-brain axis might be the important mediator in the process of AKK producing antidepressants effects.
Insights
Akkermansia muciniphila (AKK) probiotic improved depressive-like behaviors in mice by restoring gut microbiome and lipid metabolism in the gut-brain axis. This suggests AKK
Area of Science:
- Microbiome research
- Neuroscience
- Metabolomics
Background:
- Akkermansia muciniphila (AKK) is a potential probiotic with previously observed neuroprotective effects.
- Previous studies indicated AKK alleviates depressive-like behaviors (DLBs) by inhibiting neuroinflammation.
- This study investigates AKK's antidepressant effects by examining metabolic activities within the gut-brain axis.
Purpose of the Study:
- To investigate the antidepressant effects of Akkermansia muciniphila (AKK) in a mouse model of depression.
- To explore the impact of AKK on metabolic activities and gut microbiome alterations in the gut-brain axis.
- To identify potential mechanisms underlying AKK's antidepressant properties, focusing on lipid metabolism and neuroinflammation.
Main Methods:
- A chronic restraint stress (CRS) model was established to induce depressive-like behaviors in mice.
- Mice were treated with AKK for three weeks, and subsequent analyses included gut microbiome profiling, intestinal permeability markers (Claudin-1, Occludin), and metabolomics.
- Inflammation-related factors (FFAR3, p-p65) in the hippocampus were measured.
Main Results:
- AKK treatment successfully colonized the gut and significantly improved depressive-like behaviors in CRS mice.
- AKK administration restored gut microbiome balance, increased intestinal permeability proteins (Claudin-1, Occludin), and normalized lipid metabolism, particularly glycerophospholipid metabolism, across the gut-brain axis.
- Hippocampal analysis revealed increased FFAR3 and decreased phosphorylated NF-κB p65 (p-p65) in AKK-treated mice.
Conclusions:
- Akkermansia muciniphila (AKK) demonstrates antidepressant effects by improving gut microbiome, intestinal permeability, and lipid metabolism.
- Glycerophospholipid metabolism within the gut-brain axis appears to be a key mediator of AKK's antidepressant actions.
- AKK may exert its effects by modulating lipid metabolism and reducing neuroinflammation in the hippocampus.
Related Concept Videos
01:22Gut-Brain Axis
01:23Antidepressant Drugs: MAOIs and Other Agents