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Updated: Jun 8, 2026
Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination
Published on: September 12, 2016
Akkermansia muciniphila Modulates Central Nervous System Autoimmune Response and Cognitive Impairment by Inhibiting
Xiaobing Li1,2,3, Dengna Lin4,5, Xin Hu1,2,3
1Department of Neurology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Background:
Numerous studies have demonstrated the significant role of Akkermansia muciniphila (A. muciniphila) in enhancing host immune responses and metabolic functions. However, its increased presence in multiple sclerosis (MS) patients has led to a focus on the relationships between A. muciniphila and diseases, with the underlying mechanisms remaining unknown.
Method:
Solochrome cyanin, hematoxylin-eosin staining (H&E) and immunofluorescence staining were used to assess demyelination and inflammation. Gut microbiota changes were examined by 16S rRNA sequencing. Intracellular cytokine levels were assessed by flow cytometry. Cognitive impairment was evaluated using four behavioral tests. Intestinal barrier function and pyrin domain-containing protein 3 (NLRP3)-mediated neuroinflammation were evaluated by immunoblotting.
Results:
We found that treatment with an appropriate dose of A. muciniphila (5.0 × 107 CFU/mL) reduced neuropathology and disease severity in experimental autoimmune encephalomyelitis (EAE) mice. In addition, A. muciniphila supplementation increased the diversity and abundance of intestinal microbiota while decreasing the Firmicutes/Bacteroidetes ratio. Moreover, it improved intestinal barrier function and attenuated Th17 responses in the gut, central nervous system (CNS), and lymphoid tissues, without affecting Treg response in the lymphoid tissue. Furthermore, A. muciniphila administration partly regulated cognitive impairment and hippocampal NLRP3-mediated neuroinflammation.
Conclusion:
Our results suggest that A. muciniphila holds promise as a probiotic for treating NLRP3-associated inflammatory disorders and cognitive impairment, including MS.
Insights
Akkermansia muciniphila (A. muciniphila) supplementation reduced disease severity in mice with experimental autoimmune encephalomyelitis. This probiotic improved gut barrier function and cognitive impairment by modulating neuroinflammation.
Area of Science:
- Microbiology
- Immunology
- Neuroscience
Background:
- Akkermansia muciniphila (A. muciniphila) is known to enhance immune and metabolic functions.
- Increased A. muciniphila presence in multiple sclerosis (MS) patients suggests a link to disease, but mechanisms are unclear.
Purpose of the Study:
- To investigate the therapeutic potential of A. muciniphila in a mouse model of MS.
- To elucidate the mechanisms underlying A. muciniphila's effects on neuropathology, gut microbiota, and neuroinflammation.
Main Methods:
- Assessed demyelination and inflammation using histological staining (H&E, immunofluorescence).
- Analyzed gut microbiota composition via 16S rRNA sequencing.
- Evaluated immune responses, cognitive function, intestinal barrier integrity, and NLRP3-mediated neuroinflammation.
Main Results:
- A. muciniphila treatment reduced neuropathology and disease severity in experimental autoimmune encephalomyelitis (EAE) mice.
- Supplementation enhanced gut microbiota diversity, improved intestinal barrier function, and attenuated Th17 responses.
- A. muciniphila administration partly ameliorated cognitive impairment and hippocampal NLRP3-mediated neuroinflammation.
Conclusions:
- A. muciniphila demonstrates potential as a probiotic for treating NLRP3-associated inflammatory disorders.
- The findings suggest A. muciniphila may be beneficial for cognitive impairment, including in MS.
