使用模式鼠探討益生菌Lacticaseibacillus paracasei PS23對阿茲海默症的腸道微生物與海馬迴基因表現影響

Abstract

阿茲海默症 (Alzheimer’s Disease, AD) 是最常見的神經退化性疾病之一，影響患者記憶、思考和行為。研究指出腸道和大腦之間有一個雙向的通道，稱為腸腦軸。近期越來越多研究指出腸道菌群的失調與AD有關聯，但腸道菌群在AD發病機制的作用仍有許多未明之處。此外有研究發現，益生菌可以通過腸腦軸改善腸道菌群的失調進而調整腦部功能。 Lacticaseibacillus paracasei PS23 是一種從健康人類糞便中分離出來的益生菌，多項研究指出PS23可以改善認知功能、衰老和憂鬱症。然而，PS23 對 AD 的影響仍未有報導。我們在稍早的研究中已經確認PS23可以改善AD小鼠之認知功能，在此研究中，我們分析益生菌 PS23 是否改變AD模式小鼠腸道微生物群組成和海馬迴基因表達。我們發現PS23能提升AD小鼠代謝、免疫功能、以及短鏈脂肪酸相關的腸道微生物群豐度。另外，PS23活菌也有提升短鏈脂肪酸的濃度。PS23活菌以及熱殺菌皆有改變SRP54、P2Y2R、growth hormone、prolactin的基因表達程度。因此，我們推測PS23活菌可以透過增加短鏈脂肪酸而降低AD小鼠中的發炎，而PS23熱殺菌可能以透過提升growth hormone來增加神經新生，而PS23活菌以及熱殺菌可能透過增加prolactin表現量而增加記憶及認知功能以改善AD之病徵。綜合上述結果，我們認為PS23具有預防與治療AD的潛力。Alzheimer’s disease (AD) is the most common form of dementia that affects memory, thinking, and behaviors. Studies have proved that there is a bidirectional communication between the gut and the brain, known as the gut-brain axis. Studies have shown that probiotics can affect the brain functions through the gut-brain axis. Recently, there has been increasing evidence indicate the association between gut dysbiosis and AD, but the role of gut microbiota in AD pathogenesis remains elusive. Lacticaseibacillus paracasei PS23 is a probiotic that was isolated from healthy human feces, and several studies suggest that PS23 can ameliorate cognitive decline, aging progression, and depression. However, the effect of PS23 on AD remains to be studied. Our previous study has indicated that PS23 can improve the cognition of AD model mice. Here, we investigated whether probiotic PS23 changed the gut microbiota composition and gene expression in hippocampi of AD model mice. PS23 did increase the abundance of microbiota related with metabolism, immune functions, and short chain fatty acids in AD mice. Also, live-PS23 (L-PS23) increases the amount of short chain fatty acids (SCFAs). In addition, PS23 alters genes expression of SRP54, P2Y2R, growth hormone, and prolactin in the mouse hippocampus. These results suggest that L-PS23 might decrease inflammation by increasing the production of SCFAs in AD mice, and heat-killed PS23 (H-PS23) increases neurogenesis might be through increasing gene expression of growth hormone and alter the abundance of microbiota in AD mice. The administration of both L-PS23 and H-PS23 may increase the memory and cognition by increasing the gene expression of prolactin. PS23 could be a potential preventative and therapeutic probiotics for AD.