Crown Princess Victoria's Children's Hospital, Region Östergötland, Linköping, Sweden.
Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
Diabetologia. 2023 Jun;66(6):1116-1128. doi: 10.1007/s00125-023-05895-7. Epub 2023 Mar 25.
AIMS/HYPOTHESIS: While autoantibodies are traditional markers for type 1 diabetes development, we identified gut microbial biomarkers in 1-year-old infants associated with future type 1 diabetes up to 20 years before diagnosis.
Infants enrolled in the longitudinal general population cohort All Babies In Southeast Sweden (ABIS) provided a stool sample at a mean age of 12.5 months. Samples (future type 1 diabetes, n=16; healthy controls, n=268) were subjected to 16S ribosomal RNA (rRNA) sequencing and quantitative PCR. Microbial differences at the taxonomic and core microbiome levels were assessed. PICRUSt was used to predict functional content from the 16S rRNA amplicons. Sixteen infants, with a future diagnosis of type 1 diabetes at a mean age of 13.3±5.4 years, and one hundred iterations of 32 matched control infants, who remained healthy up to 20 years of age, were analysed.
Parasutterella and Eubacterium were more abundant in healthy control infants, while Porphyromonas was differentially more abundant in infants with future type 1 diabetes diagnosis. Ruminococcus was a strong determinant in differentiating both control infants and those with future type 1 diabetes using random forest analysis and had differing trends of abundance when comparing control infants and those with future type 1 diabetes. Flavonifractor and UBA1819 were the strongest factors for differentiating control infants, showing higher abundance in control infants compared with those with future type 1 diabetes. Alternatively, Alistipes (more abundant in control infants) and Fusicatenibacter (mixed abundance patterns when comparing case and control infants) were the strongest factors for differentiating future type 1 diabetes. Predicted gene content regarding butyrate production and pyruvate fermentation was differentially observed to be higher in healthy control infants.
CONCLUSIONS/INTERPRETATION: This investigation suggests that microbial biomarkers for type 1 diabetes may be present as early as 1 year of age, as reflected in the taxonomic and functional differences of the microbial communities. The possibility of preventing disease onset by altering or promoting a 'healthy' gut microbiome is appealing.
The forward and reverse 16S raw sequencing data generated in this study are available through the NCBI Sequence Read Archive under BioProject PRJNA875929. Associated sample metadata used for statistical comparison are available in the source data file. R codes used for statistical comparisons and figure generation are available at: https://github.com/PMilletich/T1D_Pipeline .
目的/假设：虽然自身抗体是 1 型糖尿病发展的传统标志物，但我们在 1 岁婴儿中鉴定出了与未来 20 年诊断前的 1 型糖尿病相关的肠道微生物生物标志物。
参加瑞典东南所有婴儿纵向一般人群队列（ABIS）的婴儿在平均 12.5 个月时提供粪便样本。样本（未来的 1 型糖尿病，n=16；健康对照组，n=268）进行了 16S 核糖体 RNA（rRNA）测序和定量 PCR。在分类和核心微生物组水平评估了微生物差异。使用 PICRUSt 从 16S rRNA 扩增子预测功能含量。分析了 16 名未来在平均年龄 13.3±5.4 岁时被诊断为 1 型糖尿病的婴儿和 100 次迭代的 32 名匹配的健康对照组婴儿，这些婴儿在 20 岁之前保持健康。
在健康对照组婴儿中，Parasutterella 和 Eubacterium 更为丰富，而 Porphyromonas 在未来诊断为 1 型糖尿病的婴儿中差异更为丰富。随机森林分析表明，Ruminococcus 是区分对照组婴儿和未来患有 1 型糖尿病婴儿的重要决定因素，并且当比较对照组婴儿和未来患有 1 型糖尿病婴儿时，其丰度呈现出不同的趋势。Flavonifractor 和 UBA1819 是区分对照组婴儿的最强因素，与未来患有 1 型糖尿病的婴儿相比，对照组婴儿的丰度更高。相反，Alistipes（在对照组婴儿中更为丰富）和 Fusicatenibacter（在比较病例和对照组婴儿时丰度混合模式）是区分未来患有 1 型糖尿病的最强因素。丁酸产生和丙酮酸发酵的预测基因含量差异观察到在健康对照组婴儿中更高。
结论/解释：这项研究表明，1 型糖尿病的微生物生物标志物可能早在 1 岁时就存在，反映在微生物群落的分类和功能差异中。通过改变或促进“健康”肠道微生物组来预防疾病发作的可能性是吸引人的。
本研究生成的正向和反向 16S 原始测序数据可通过 NCBI 序列读取档案获得，编号为 BioProject PRJNA875929。用于统计比较的相关样本元数据可在源数据文件中获得。用于统计比较和生成图的 R 代码可在：https://github.com/PMilletich/T1D_Pipeline 获得。
