腸道菌對於飲食限制增強記憶功能之研究

Abstract

飲食節制在許多模式生物上都被證實具有延緩老化、抗發炎、抗肥胖及提升記憶功能的效果。我們實驗室先前藉由小鼠記憶行為實驗針對飲食節制的效果做 更近一步的分析，發現飲食限制會透過調控腦中血清素受體來達到記憶功能提升 的效果，然而飲食限制是透過何種路徑影響到大腦並不清楚。先前其他研究指出 飲食限制會藉由改變腸道菌相藉以達成抗肥胖等功效。同時，腸道菌相被認為會 透過所謂腸-腦軸線來影響大腦發育及行為功能。 在本實驗中，我們假設飲食限制亦是透過調控腸道菌相進而導致大腦中神經 細胞產生結構及功能上的變化，最後行為上表現出增強記憶功能。 我們透過抗生素處理的小鼠以及無菌小鼠兩種小鼠模式進行實驗，發現飲食 限制無法引發兩者之記憶功能提升與神經細胞樹突結構的改變。綜合以上結果可 知，飲食限制增強記憶力之效果的確是需要腸道菌相。為了證實其中的因果關係， 我們將飲食節制小鼠糞便中萃取出之菌相餵給正常飲食的小鼠，發現亦可提高記 憶功能表現，並引發神經細胞樹突結構的改變。 未來我們將近一步探討腸道菌相是否藉由迷走神經或是血液中代謝物等面向 影響大腦，並透過近一步的腸道菌相分析找到能夠提升記憶功能的關鍵菌種。

Dietary restriction (DR) is one of the most powerful regimens to improve the physiological condition. Various beneficial effects including anti-inflammation, longevity, and cognitive function were reported in multiple model organisms. We have previously demonstrated DR improves memory performance in mice although the underlying mechanism is not fully understood. Recent studies demonstrated DR modulates gut microbiota to exert various beneficial effects. In this study, we hypothesize that the microbiota-gut-brain axis plays a critical role in DR-induced memory enhancement. We adopted antibiotic-treated mice and germ-free mice as our experimental model. We demonstrated that DR-induced memory enhancement as well as structural alteration of hippocampal neurons is abolished by the removal of gut microbiota. More importantly, these DR-induced neurobehavioral effects could be accomplished by oral gavage of DR-derived fecal content without actually performing DR. Overall, our data demonstrated that the beneficial effects induced by DR were associated with the modulation of gut microbiota. The ongoing experiments are aimed to investigate several aspects of the gut-brain axis that responsible for DR-induced memory enhancement.