한빛사논문
- 조회461
Eun Ji Kang1†, Min-Gi Cha2†, Goo-Hyun Kwon2†, Sang Hak Han3, Sang Jun Yoon2, Sang Kyu Lee4, Moo Eob Ahn5, Sung-Min Won2*†, Eun Hee Ahn1,6*† and Ki Tae Suk2*†
1Department of Physiology, College of Medicine, Hallym University, Hallymdaehak-Gil 1, Chuncheon-Si, Gangwon-Do 24252, South Korea.
2Institute for Liver and Digestive Diseases, Hallym University College of Medicine, Chuncheon-Si, Gangwon-Do 24253, South Korea.
3Department of Pathology, College of Medicine, Hallym University, Hallymdaehak-Gil 1, Chuncheon-Si, Gangwon-Do 24252, South Korea.
4Department of Psychiatry, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon-si, Gangwon-Do, 24253 Chuncheon-Si, South Korea.
5Department of Emergency Medicine, Hallym University, Chuncheon Sacred Heart Hospital, Chuncheon-Si, Gangwon-Do 24253, South Korea.
6Department of Neurology, College of Medicine, Hallym University, Hallymdaehak-Gil 1, Chuncheon-Si, Gangwon-Do 24252, South Korea.
†Eun Ji Kang, Min-Gi Cha, Goo-Hyun Kwon, Sung-Min Won, Eun Hee Ahn and Ki Tae Suk contributed equally to this work.
*Correspondence: Sung-Min Won, Eun Hee Ahn, Ki Tae Suk
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.
논문정보
- Research article
- 2024년 09월 (BRIC 등록일 2024-09-30)
- 국내 연구진
- 의약학 > 신경의학
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