Dysregulated microbial metabolites in brain of mice with type 1 diabetes mellitus-induced cognitive impairment

doi:10.3969/j.issn.1006-7795.2022.04.017

Abstract

Abstract: Objective To investigate the changes of intestinal microflora metabolites in brain tissue of type 1 diabetes mellitus (T1DM)mice with cognitive impairment. Methods To develop a T1DM model, male C57BL/6 mice aged 6 weeks were given by intraperitoneal injection of STZ at dosage 40 mg/kg of body weight for five consecutive days. The Morris water maze test was used to assess learning and memory ability in mice. An ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system was applied to identify and quantify microbiota-derived metabolites in brain samples collected from sacrificed mice. Results The gut microbial metabolic profiles in brains of diabetes mellitus (DM) mice differed significantly from controls. Compared with control mice, brain levels of glutamine (Log₂FC=0.262,P=0.002), tartaric acid (Log₂FC=0.847,P=0.017), lactic acid (Log₂FC=0.326,P=0.002) and m-aminobenzoic acid (Log₂FC=1.028,P=0.046) were significantly higher (all Log₂FC>0, P<0.05) while indolelactic acid, 3-hydroxybutyric acid (Log₂FC=-1.466,P=0.049) and other 5 metabolites were significantly lower (all Log₂FC<0, P<0.05) in DM mice. Such metabolic differences encompassed pyrimidine metabolism, D-glutamine and D-glutamate metabolism, pyruvate metabolism, purine metabolism and other metabolic pathways. Conclusion Gut microbiome and its metabolites may play a crucial role in the onset and development of type 1 diabetes-induced cognitive impairment. Targeting the gut microbiome and relevant microbiota-derived metabolites would be effective therapeutic treatments for T1DM-induced cognitive impairment.

Key words: type 1 diabetes mellitus, cognitive impairment, microbiota-derived metabolites, Meta-omics

CLC Number:

R587

An Yu, Bian Nannan, Ding Xiaoyu, Chang Xiaona, Liu Jia, Wang Guang. Dysregulated microbial metabolites in brain of mice with type 1 diabetes mellitus-induced cognitive impairment[J]. Journal of Capital Medical University, 2022, 43(4): 622-629.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2022.04.017

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2022/V43/I4/622

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