Probiotic-Derived Extracellular Vesicles Reverse Neuroinflammation and Boost Brain Function in Liver Disease
A groundbreaking study by Vicente Felipo at the Neurobiology Laboratory, Centro Investigación Príncipe Felipe, Spain, reveals that extracellular vesicles (EVs) from Lacticaseibacillus paracasei can significantly reduce neuroinflammation in the hippocampus and restore cognitive function in a hyperammonemic rat model of minimal hepatic encephalopathy (MHE).
MHE, a complication of cirrhosis associated with elevated blood ammonia levels, leads to cognitive impairment and reduced quality of life. Hyperammonemia contributes to neuroinflammation and altered glutamatergic neurotransmission, key factors in MHE pathology.
This study demonstrates that intravenous administration of L. paracasei EVs reverses glial activation and neuroinflammation in the hippocampus of hyperammonemic rats. Ex vivo analyses show that hyperammonemia disrupts TNFα-TNFR1-S1PR2-IL-1β-CCL2-BDNF-TrkB signaling, leading to an imbalance in neurotransmitter receptors, increased NR2B and GluA2 membrane expression, and reduced GluA1 expression. These changes impair learning and memory. Treatment with L. paracasei EVs restores this signaling balance, normalizing glutamatergic neurotransmission and significantly improving cognitive function.
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L. paracasei EVs effectively counteract neuroinflammation in the hippocampus.
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They restore balance in the TNFα-TNFR1-S1PR2-IL-1β-CCL2-BDNF-TrkB signaling pathway.
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They normalize disruptions in glutamatergic neurotransmission caused by hyperammonemia.
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Memory and learning abilities show significant recovery following treatment.
A New Hope for MHE Treatment:
These findings suggest that L. paracasei EVs could serve as a novel, safe therapeutic strategy to improve cognitive function in cirrhotic patients with MHE.
For more details, read the full study: DOI: 10.1016/j.micres.2025.128101.
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