Akkermansia Muciniphila Improve Cognitive Dysfunction by Regulating BDNF and Serotonin Pathway in Gut-liver-brain Axis

Overview

Journal Microbiome

Publisher Biomed Central

Specialties Genetics
Microbiology

Date 2024 Sep 28

PMID 39342324

Authors

Eun Ji Kang

Min-Gi Cha

Goo-Hyun Kwon

Sang Hak Han

Sang Jun Yoon

Sang Kyu Lee

Moo Eob Ahn

Sung-Min Won

Eun Hee Ahn

Ki Tae Suk

Affiliations

Soon will be listed here.

Abstract

Backrground: Akkermansia muciniphila, a next-generation probiotic, is known as a cornerstone regulating the gut-organ axis in various diseases, but the underlying mechanism remains poorly understood. Here, we revealed the neuronal and antifibrotic effects of A. muciniphila on the gut-liver-brain axis in liver injury.

Results: To investigate neurologic dysfunction and characteristic gut microbiotas, we performed a cirrhosis cohort (154 patients with or without hepatic encephalopathy) and a community cognition cohort (80 participants in one region for three years) and validated the existence of cognitive impairment in a 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced hepatic injury mouse model. The effects of the candidate strain on cognition were evaluated in animal models of liver injury. The expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors was accessed in patients with fibrosis (100 patients) according to the fibrosis grade and hepatic venous pressure gradient. The proportion of A. muciniphila decreased in populations with hepatic encephalopathy and cognitive dysfunction. Tissue staining techniques confirmed gut-liver-brain damage in liver injury, with drastic expression of BDNF and serotonin in the gut and brain. The administration of A. muciniphila significantly reduced tissue damage and improved cognitive dysfunction and the expression of BDNF and serotonin. Isolated vagus nerve staining showed a recovery of serotonin expression without affecting the dopamine pathway. Conversely, in liver tissue, the inhibition of injury through the suppression of serotonin receptor (5-hydroxytryptamine 2A and 2B) expression was confirmed. The severity of liver injury was correlated with the abundance of serotonin, BDNF, and A. muciniphila.

Conclusions: A. muciniphila, a next-generation probiotic, is a therapeutic candidate for alleviating the symptoms of liver fibrosis and cognitive impairment.

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