Microbial taxonomic and functional shifts in adolescents with type 1 diabetes are associated with clinical and dietary factors.

Microbial taxonomic and functional shifts in adolescents with type 1 diabetes are associated with clinical and dietary factors.
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DOI:
10.1016/j.ebiom.2023.104641
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发表时间:
2023-07
期刊:
影响因子:
11.1
通讯作者:
Babu, Pon Velayutham Anandh
Babu, Pon Velayutham Anandh
中科院分区:
医学1区
文献类型:
--
作者:
Mokhtari, Pari;Jambal, Puujee;Metos, Julie M.;Shankar, Kartik;Babu, Pon Velayutham Anandh

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有证据表明1型糖尿病(T1D)的发病机制与肠道微生物组之间存在联系。然而,微生物代谢途径的调节以及T1D中细菌种类与饮食因素的关联在很大程度上是未知的。我们调查了T1D青少年的微生物宏基因组特征是否与临床/饮食因素相关。招募了患有T1D的青少年(病例)和健康青少年(对照),并使用鸟枪宏基因组测序对参与者的粪便样本进行了微生物组分析。bioBakery3管道(Kneaddata、Metaphlan 4和HUMANN)用于分配分类和功能注释。收集临床(HbA1c)和饮食信息(3天食物记录),使用斯皮尔曼相关性进行关联分析。患有T1D的青少年在肠道微生物组的分类组成方面表现出适度的变化。19种微生物代谢途径在T1D中改变,包括下调维生素(B2/黄素、B7/生物素和B9/叶酸)、酶辅因子(NAD+和s-腺苷甲硫氨酸)和氨基酸(天冬氨酸、天冬酰胺和赖氨酸)的生物合成,同时上调发酵途径。此外,与饮食和临床因素相关的细菌种类在健康青少年和T1D青少年之间存在差异。监督模型建模确定了预测T1D状态的分类群,最重要的特征包括粪球菌和链球菌。我们的研究为T1D青少年的微生物和代谢特征的改变提供了新的见解,表明维生素,酶辅因子和氨基酸的微生物生物合成可能在T1D中发生潜在的改变。研究补助金/:R01AT010247和/:2019 - 67017 - 29253;和助学金。
Evidence indicates a link between the pathogenesis of type 1 diabetes (T1D) and the gut microbiome. However, the regulation of microbial metabolic pathways and the associations of bacterial species with dietary factors in T1D are largely unknown. We investigated whether microbial metagenomic signatures in adolescents with T1D are associated with clinical/dietary factors. Adolescents with T1D (case) and healthy adolescents (control) were recruited, and microbiome profiling in participants' stool samples was performed using shotgun metagenomic sequencing. The bioBakery3 pipeline (Kneaddata, Metaphlan 4 and HUMAnN) was used to assign taxonomy and functional annotations. Clinical (HbA1c) and dietary information (3-day food record) were collected for conducting association analysis using Spearman's correlation. Adolescents with T1D exhibited modest changes in taxonomic composition of gut microbiome. Nineteen microbial metabolic pathways were altered in T1D, including downregulation of biosynthesis of vitamins (B2/flavin, B7/biotin and B9/folate), enzyme cofactors (NAD+ and s-adenosyl methionine) and amino acids (aspartate, asparagine and lysine) with an upregulation in the fermentation pathways. Furthermore, bacterial species associated with dietary and clinical factors differed between healthy adolescents and adolescents with T1D. Supervised models modeling identified taxa predictive of T1D status, and the top features included Coprococcus and Streptococcus. Our study provides new insight into the alteration of microbial and metabolic signatures in adolescents with T1D, suggesting that microbial biosynthesis of vitamins, enzyme cofactors and amino acids may be potentially altered in T1D. Research grants from /: R01AT010247 and /: 2019-67017-29253; and Assistantship.
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