Urinary metabolomic changes and microbiotic alterations in presenilin1/2 conditional double knockout mice

Journal of Translational Medicine

Qixue Wang¹  Mingmei Zhou¹  Nian Zhou¹  Mengna Lu²  Chenyi Xia³  Ying Xu³  Yongkang Wu³  Jie Gao⁴ 

[1] Center for Chinese Medicine Therapy and Systems Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong District, 201203, Shanghai, China;Center for Chinese Medicine Therapy and Systems Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong District, 201203, Shanghai, China;School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, 201203, Shanghai, China;Department of Physiology, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, 201203, Shanghai, China;Department of Physiology, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, 201203, Shanghai, China;Department of Rehabilitation Medicine, Affiliated Hospital of Nantong University, 20 Xisi Road, 226001, Nantong, Jiangsu, China;

关键词: Alzheimer’s disease;    PS cDKO mice;    Metabolomics;    Gut microbiota;    16S rRNA sequencing;   

DOI  :  10.1186/s12967-021-03032-9

来源: Springer

【 摘 要 】

BackgroundGiven the clinical low efficient treatment based on mono-brain-target design in Alzheimer’s disease (AD) and an increasing emphasis on microbiome-gut-brain axis which was considered as a crucial pathway to affect the progress of AD along with metabolic changes, integrative metabolomic signatures and microbiotic community profilings were applied on the early age (2-month) and mature age (6-month) of presenilin1/2 conditional double knockout (PS cDKO) mice which exhibit a series of AD-like phenotypes, comparing with gender and age-matched C57BL/6 wild-type (WT) mice to clarify the relationship between microbiota and metabolomic changes during the disease progression of AD.Materials and methodsUrinary and fecal samples from PS cDKO mice and gender-matched C57BL/6 wild-type (WT) mice both at age of 2 and 6 months were collected. Urinary metabolomic signatures were measured by the gas chromatography-time-of-flight mass spectrometer, as well as 16S rRNA sequence analysis was performed to analyse the microbiota composition at both ages. Furthermore, combining microbiotic functional prediction and Spearman’s correlation coefficient analysis to explore the relationship between differential urinary metabolites and gut microbiota.ResultsIn addition to memory impairment, PS cDKO mice displayed metabolic and microbiotic changes at both of early and mature ages. By longitudinal study, xylitol and glycine were reduced at both ages. The disturbed metabolic pathways were involved in glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions, starch and sucrose metabolism, and citrate cycle, which were consistent with functional metabolic pathway predicted by the gut microbiome, including energy metabolism, lipid metabolism, glycan biosynthesis and metabolism. Besides reduced richness and evenness in gut microbiome, PS cDKO mice displayed increases in Lactobacillus, while decreases in norank_f_Muribaculaceae, Lachnospiraceae_NK4A136_group, Mucispirillum, and Odoribacter. Those altered microbiota were exceedingly associated with the levels of differential metabolites.ConclusionsThe urinary metabolomics of AD may be partially mediated by the gut microbiota. The integrated analysis between gut microbes and host metabolism may provide a reference for the pathogenesis of AD.

【 授权许可】

CC BY