Previous studies suggest that the human gut microbiome is dysregulated in islet autoimmunity, preceding the clinical onset of type 1 diabetes (T1D). The microbiota of the gut plays an important role in the regulation of bile acid (BA) metabolism. However, not much is known about the regulation of BAs during progression to T1D. Here, we analyzed BAs in a longitudinal series of serum (n= 333) and stool (n= 304) samples, collected at 3, 6, 12, 18, 24 and 36 months of age, from children who developed a single islet autoantibody (P1Ab), multiple islet autoantibodies (P2Ab), and controls (CTRs) who remained autoantibody (AAb) negative during the follow-up. In addition, we analyzed the stool microbiome by shotgun metagenomics in a subgroup of these children (n=111). Factor analysis showed that age had the strongest impact on BA and microbiome profiles. We found that, at an early age, the systemic BA (including taurine and glycine conjugates) and microbial secondary BA pathways were altered in the P2Ab group as compared to the P1Ab or CTR groups. Our findings thus suggest that dysregulated BA metabolism in early life may contribute to the risk and pathogenesis of T1D.

中文翻译：

---

肠道微生物组的动力学——介导的胆汁酸代谢进展为胰岛自身免疫

先前的研究表明，在 1 型糖尿病 (T1D) 临床发作之前，人类肠道微生物群在胰岛自身免疫中失调。肠道微生物群在调节胆汁酸 (BA) 代谢中起重要作用。然而，在进展为 T1D 期间对 BA 的调节知之甚少。在这里，我们分析了在 3、6、12、18、24 和 36 个月大时收集的一系列血清（n = 333）和粪便（n = 304）样本中的 BAs，这些样本来自开发了单一胰岛自身抗体的儿童(P1Ab)、多种胰岛自身抗体 (P2Ab) 和在随访期间保持自身抗体 (AAb) 阴性的对照 (CTR)。此外，我们通过鸟枪法宏基因组学分析了这些儿童亚组 (n=111) 的粪便微生物组。因子分析表明，年龄对 BA 和微生物组谱的影响最大。我们发现，在早期，与 P1Ab 或 CTR 组相比，P2Ab 组的全身 BA（包括牛磺酸和甘氨酸结合物）和微生物次级 BA 途径发生了改变。因此，我们的研究结果表明，生命早期的 BA 代谢失调可能导致 T1D 的风险和发病机制。