以大鼠模型探討第二代抗精神病藥物對腸道微生物菌相與代謝相關指數的影響

劉育安

doi:10.6342/NTU201900108

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以大鼠模型探讨第二代抗精神病药物对肠道微生物菌相与代谢相关指数的影响

The Effect of Second-Generation Antipsychotics to Gut Microbiome and Metabolic Index in Rat Model

刘育安 , 硕士　　导师：林亮音　　共同指导教授：刘韵如

繁体中文 DOI： 10.6342/NTU201900108

思觉失调症；非典型抗精神病药物；第二代抗精神病药物；代谢性症候群；肠道微生物菌相； Olanzapine ； Aripiprazole (Abilify) ； schizophrenia ； atypical antipsychotics ； second-generation antipsychotics ； metabolic syndrome ； gut microbiota ； olanzapine ； aripiprazole (abilify)

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Patients with schizophrenia suffer from two-fold to three-fold higher mortality rates compared with the general population. Metabolic syndrome and cardiovascular disease due to the side effect of second-generation antipsychotics become the major causes of mortality. Furthermore, several studies have indicated found that schizophrenia and metabolic syndrome both represent chronic systemic inflammation. In addition, recent studies have reported that gut microbiota play a critical role in development of psychotic disease and metabolic syndrome. Thus, we investigated the impact of olanzapine (OLZ) and aripiprazole (ARI) treatment on metabolic, inflammatory and gut microbiome parameters.
In this study, we treated female Sprague–Dawley rats with OLZ, ARI and saline by oral gavage for 6 weeks. We found that OLZ and ARI both induced significant body weight gain and increased abdominal subcutaneous and visceral fat; however, the effect was independent of food intake and hedonic hunger test. OLZ and ARI group tended to reduce locomotor activity compare to mock. In addition, OLZ down-regulated expression of hepatic Srebp-1c, Acc and Fas mRNA, whereas ARI only reduced Acc and Fas mRNA expression. Besides, analysis of CD68 mRNA expression indicated that OLZ and ARI induced macrophage infiltration in adipose tissue. Nevertheless, plasma glucose, triglyceride, total-cholesterol, HDL-C, insulin, cytokines and diabetes markers were not affected by ARI or OLZ. Only plasma MIP-3a significantly reduced in OLZ and ARI group.
On the other hand, we analyzed mock gut mucosal and stool microbiota at first, and found that the species richness and microbiota composition displayed similar distribution among mucosa of caecum, colon and rectum, and caecal, colonic, rectal stool microbiota composition also showed similar distribution, whereas microbiota composition was significant difference between mucosa and stool, and probiotics seem to mainly survive in large intestine mucosa. Following OLZ and ARI treatment, decrease of species richness (α-diversity) and altered microbiota profile (β-diversity) were observed in caecal stool and mucosa, especially significant in caecal mucosa.
In this study, we found that the species richness of rat caecal mucosa was decreased and the microbiota composition was altered into obesity- or metabolic syndrome-related microbiota profile in animal models or human. This finding indicated gut microbiota play a critical role in the underlying mechanism of second-generation antipsychotics induced obesity.

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引用含有DOI的文献

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。 如想对DOI的使用与概念有进一步了解，请参考 （ ） 。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。