Unit of Human Microbiome, Multimodal Laboratory Medicine Research Area, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
Diabetes & Growth Disorders Unit, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
Int J Mol Sci. 2022 Dec 15;23(24):15982. doi: 10.3390/ijms232415982.
Type 1 diabetes (T1D) is a chronic autoimmune metabolic disorder with onset in pediatric/adolescent age, characterized by insufficient insulin production, due to a progressive destruction of pancreatic β-cells. Evidence on the correlation between the human gut microbiota (GM) composition and T1D insurgence has been recently reported. In particular, 16S rRNA-based metagenomics has been intensively employed in the last decade in a number of investigations focused on GM representation in relation to a pre-disease state or to a response to clinical treatments. On the other hand, few works have been published using alternative functional omics, which is more suitable to provide a different interpretation of such a relationship. In this work, we pursued a comprehensive metaproteomic investigation on T1D children compared with a group of siblings (SIBL) and a reference control group (CTRL) composed of aged matched healthy subjects, with the aim of finding features in the T1D patients' GM to be related with the onset of the disease. Modulated metaproteins were found either by comparing T1D with CTRL and SIBL or by stratifying T1D by insulin need (IN), as a proxy of β-cells damage, showing some functional and taxonomic traits of the GM, possibly related to the disease onset at different stages of severity.
1 型糖尿病(T1D)是一种慢性自身免疫代谢紊乱疾病,发病于儿童/青少年时期,其特征是由于胰腺 β 细胞的进行性破坏,导致胰岛素产生不足。最近有证据表明,人类肠道微生物群(GM)组成与 T1D 发病之间存在相关性。特别是,在过去十年中,基于 16S rRNA 的宏基因组学已被广泛应用于多项研究中,这些研究集中于 GM 与疾病前状态或对临床治疗的反应之间的关系。另一方面,使用替代功能组学的研究较少,而后者更适合对这种关系提供不同的解释。在这项工作中,我们对 T1D 患儿进行了全面的宏蛋白质组学研究,与一组兄弟姐妹(SIBL)和由年龄匹配的健康受试者组成的参考对照组(CTRL)进行了比较,目的是在 T1D 患者的 GM 中找到与疾病发病相关的特征。通过比较 T1D 与 CTRL 和 SIBL,或者通过根据胰岛素需求(IN)对 T1D 进行分层(IN 是 β 细胞损伤的替代物),我们发现了一些被调节的宏蛋白质,这些蛋白质显示了 GM 的一些功能和分类特征,可能与疾病在不同严重程度阶段的发病有关。
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