Effects of LW-AFC,a new formula derived from Liuwei Dihuang decoction,on intestinal microbiome in senescence-accelerated mouse prone 8 strain,a mouse model of Alzheimer disease

Xiao-rui CHENG,Jian-hui WANG,Fu-qiang YE,Xiao-rui ZHANG,Feng LIU,Gang LIU,Ming NI,Shan-yi QIAO,Wen-xia ZHOU,Yong-xiang ZHANG

(1.State Key Laboratory of Toxicology and Medical Countermeasures,Beijing 100850,China;2.Department of TCM and Neuroimmunopharmacology,Beijing Institute of Pharmacology and Toxicology,Beijing 100850,China;3.Department of Biotechnology,Beijing Institute of Radiation Medicine,Beijing 100850,China）

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Effects of LW-AFC,a new formula derived from Liuwei Dihuang decoction,on intestinal microbiome in senescence-accelerated mouse prone 8 strain,a mouse model of Alzheimer disease

Xiao-rui CHENG1,2,Jian-hui WANG1,2,Fu-qiang YE3,Xiao-rui ZHANG1,2,Feng LIU1,2,Gang LIU1,2,Ming NI3,Shan-yi QIAO1,2,Wen-xia ZHOU1,2,Yong-xiang ZHANG1,2

(1.State Key Laboratory of Toxicology and Medical Countermeasures,Beijing 100850,China;2.Department of TCM and Neuroimmunopharmacology,Beijing Institute of Pharmacology and Toxicology,Beijing 100850,China;3.Department of Biotechnology,Beijing Institute of Radiation Medicine,Beijing 100850,China）

OBJECTIVETo investigate the effects of LW-AFC,a new formula derived from Liuwei Dihuang decoction,on gut microbiota and the behavior of learning and memory of SAMP8 mice,a mouse model of Alzheimer Disease(AD),and identify the specific intestinal microbiota correlating with cognitive ability.METHODSMorris-water maze test,novel object recognition test and shuttle-box test were conducted to observe the ability of learning and memory.16S rRNA amplicon sequencing(Illumina,San Diego,CA,USA)was employed to investigate gut microbiota.RESULTSThe treatment of LW-AFC improved cognitive impairments of SAMP8 mice,including spatial learning and memory ability,active avoidance response,and object recognition memory capability.Our data indicated that there were significantly 8 increased and 12 decreased operational taxonomic units(OTUs)in the gut microbiota of SAMP8 mice compared with senescence accelerated mouse resistant 1(SAMR1)strains,the control of SAMP8 mice.The treatment of LW-AFC altered 22(16 increased and 6 decreased)OTUs in SAMP8 mice and among them,15 OTUs could be reversed by LW-AFC treatment resulting in a microbial composition similar to that of SAMR1 mice.We further showed that there were 7(3 negative and 4 positive correlation)OTUs significantly correlated with all the three types of cognitive abilities,at the order level,including Bacteroidales,Clostridiales,Desulfovibrionales,CW040,and two unclassified orders.LW-AFC had influences on bacterial taxa correlated with the abilities of learning and memory in SAMP8 mice and restored them to SAMR1 mice.CONCLUSIONThe effects of LW-AFC on improving cognitive impairments of SAMP8 mice might be via modulating intestinal microbiome and LW-AFC could be used as a potential anti-AD agent.

Alzheimer disease;LW-AFC;Liuwei Dihuang decoction;microbiome;senescenceaccelerated mouse prone 8 strain

The project supported by National Science and Technology Major Project(2013ZX09508104,2012ZX09301003-002-001)

Wen-xia ZHOU,Tel:(010)66931625,E-mail：zhouwx@bmi.ac.cn