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Article type: Research Article
Authors: Zhou, Wena | Zhan, Libinb; * | Xu, Huiyinga | Zhang, Lijinga
Affiliations: [a] School of Traditional Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China | [b] Centre for Innovative Engineering Technology in Traditional Chinese Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, China
Correspondence: [*] Correspondence to: Prof. Libin Zhan, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, Liaoning, China. Tel./Fax: +86 24 31207358; E-mail: zlblibin2021@163.com.
Abstract: Background:Chronic psychological stress (PS) hinders the treatment of diabetes-associated cognitive decline (DACD). However, the impact of chronic PS on the risk of developing DACD remains unclear. There is growing evidence that gut flora interventions are promising targets for treating stress-related diseases. Objective:We examined whether chronic PS triggers or exacerbates the onset of DACD in rats and aimed to elucidate whether ZiBuPiYin recipe (ZBPYR) prevents and treats chronic PS-aggravated DACD by dynamically maintaining the components of the gut microbiota. Methods:We performed chronic PS (restraint, rotation, and congestion) on ZDF rats to establish a model. Cognitive function was evaluated by behavioral experiments, and activation of the hypothalamic-pituitary-adrenal axis was detected by ELISA. Weekly feces from rats were collected for 16 S RNA sequencing. Results:We found that chronic PS promoted cognitive abnormalities and exacerbated DACD phenotypes. Additionally, chronic PS altered intestinal flora diversity, dynamically elevating the abundance of Alistipes and Coprococcus; enriching Module 1 (Dorea, Blautia, Ruminococcus) and Module 48 (Blautia); and inhibiting Module 20 (Lactobacillus, SMB53), and Module 42 (Akkermansia). ZBPYR significantly alleviated hyperglycemia and cognitive impairment in chronic PS-aggravated DACD rats and dynamically reduced the abundance of Alistipes and Coprococcus; significantly enriched Module 3 (Ruminococcus) and Module 45 (Lactobacillus, Coprococcus, SMB53); and suppressed Module 2 (Lactobacillus), Module 16 (Turicibacter, Trichococcus, Lactobacillus, 02d06, Clostridium), Module 23 (Bifidobacterium), and Module 43 (Clostridium). Conclusion:ZBPYR might prevent and treat chronic PS-aggravated DACD by dynamically regulating Lactobacillus, Alistipes, and Coprococcus.
Keywords: Chronic psychological stress, diabetes-associated cognitive decline, gut microbiota, traditional Chinese medicine
DOI: 10.3233/JAD-220692
Journal: Journal of Alzheimer's Disease, vol. 90, no. 4, pp. 1465-1483, 2022
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