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自发性 2 型糖尿病食蟹猴血清微生物群和循环代谢物的特征。

Characteristics of the Serum Microbiota and Circulating Metabolites in Cynomolgus Monkeys With Spontaneous Type 2 Diabetes Mellitus.

机构信息

Sanya Research Institute of Hainan University, School of Biomedical Engineering, Hainan University, Sanya, China.

Key Laboratory of Biomedical Engineering of Hainan Province, One Health Institute, Hainan University, Haikou, China.

出版信息

J Med Primatol. 2024 Oct;53(5):e12738. doi: 10.1111/jmp.12738.

DOI:10.1111/jmp.12738
PMID:39307954
Abstract

BACKGROUND

Type 2 diabetes mellitus (T2DM) is widely recognized as a serious global public health concern with a substantial economic burden on patients, their families, and society. Accumulating evidence suggests that an etiologic role for serum microbiota and circulating metabolites in the pathogenesis of T2DM. This study aims to characterize the serum microbiota and circulating metabolites in cynomolgus monkeys with spontaneous T2DM, and provide a reference for the diagnosis and treatment of clinical T2DM.

METHODS

We collected serum samples of the 14 cynomolgus monkeys (15-20 years old, male) for serum microbiota analysis by 16S rRNA gene V3-V4 region amplicon sequencing and circulating metabolites analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry, of which seven were spontaneous T2DM cynomolgus monkeys and seven were healthy controls.

RESULTS

Our results showed that the serum microbiota abundance and diversity were significantly increased in cynomolgus monkeys with spontaneous T2DM compared to healthy controls, the phyla of Cyanobacteria and Chloroflexi and the genera of Lactobacillus, rhodobacter and collinsella were also significantly increased. A total of 114 serum differentially expressed metabolites (DEMs) were identified, of which 22 were selected as potential biomarkers candidates related to spontaneous T2DM in cynomolgus monkeys by multivariate data analysis. In addition, serum levels of total SCFAs, acetate, butyrate, caproate, isobutyrate, and isovalerate were also significantly increased in the present study. The correlation network analyses have selected certain key DEMs, such as D-Psicose, 4-Oxoproline, D-Glutamine, and Hydroxyphenyllactic acid, which may serve as potential biomarkers for distinguishing between T2DM and healthy controls.

CONCLUSION

Our results provide preliminary insights on perturbed serum microbiota and circulating metabolites of cynomolgus monkeys with spontaneous T2DM. These findings would be useful to develop microbiota-based strategies for T2DM prevention and control.

摘要

背景

2 型糖尿病(T2DM)是一种广泛存在的全球性公共卫生问题,给患者、家庭和社会带来了沉重的经济负担。越来越多的证据表明,血清微生物组和循环代谢物在 T2DM 的发病机制中起着重要作用。本研究旨在描述自发性 T2DM 食蟹猴的血清微生物组和循环代谢物特征,为临床 T2DM 的诊断和治疗提供参考。

方法

我们收集了 14 只 15-20 岁雄性食蟹猴的血清样本,通过 16S rRNA 基因 V3-V4 区扩增子测序进行血清微生物组分析,通过超高效液相色谱-串联质谱法进行循环代谢物分析,其中 7 只为自发性 T2DM 食蟹猴,7 只为健康对照。

结果

与健康对照组相比,自发性 T2DM 食蟹猴的血清微生物组丰度和多样性显著增加,蓝藻菌门和绿弯菌门以及乳杆菌属、红杆菌属和柯林斯氏菌属的丰度也显著增加。共鉴定出 114 种血清差异表达代谢物(DEMs),其中 22 种被选为与食蟹猴自发性 T2DM 相关的潜在生物标志物候选物。此外,本研究还发现血清总 SCFAs、乙酸盐、丁酸盐、己酸盐、异丁酸酯和异戊酸酯水平也显著升高。相关性网络分析还选择了某些关键的 DEMs,如 D-岩藻糖、4-氧脯氨酸、D-谷氨酰胺和对羟基苯乳酸,它们可能作为区分 T2DM 和健康对照组的潜在生物标志物。

结论

本研究初步揭示了自发性 T2DM 食蟹猴血清微生物组和循环代谢物的变化。这些发现将有助于开发基于微生物组的 T2DM 预防和控制策略。

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