Gut microbiota-derived indole-3-acetic acid suppresses high myopia progression by promoting type I collagen synthesis.

IF 13 1区 生物学 Q1 CELL BIOLOGY
Hao Li, Yu Du, Kaiwen Cheng, Yuxi Chen, Ling Wei, Yujun Pei, Xiaoyu Wang, Lan Wang, Ye Zhang, Xiaoxin Hu, Yi Lu, Xiangjia Zhu
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Abstract

High myopia (HM) is a leading cause of blindness worldwide with currently no effective interventions available. A major hurdle lies in its often isolated perception as a purely ocular morbidity, disregarding potential systemic implications. Recent evidence suggests the existence of a gut-eye axis; however, the role of gut microbiota in the pathogenesis of HM remains largely unexplored. Herein, we provide a potential crosstalk among HM's gut dysbiosis, microbial metabolites, and scleral remodeling. Utilizing 16S rRNA gene sequencing, we observed an altered gut microbiota profile in HM patients with a significant reduction in probiotic abundance compared with healthy controls. Subsequent targeted metabolic profiling revealed a notable decrease in plasma levels of the gut microbiota-derived metabolite indole-3-acetic acid (3-IAA) among HM patients, which is closely associated with the reduced probiotics, both negatively correlated with HM severity. Genetic analyses determined that gut microbiota are causally associated with myopia risk. Importantly, when mice subjected to HM modeling receive fecal microbiota transplantation from healthy donors, there is an increase in 3-IAA plasma levels and simultaneous retardation of HM progression along with better maintenance of collagen type I alpha 1 (COL1A1) expression in the sclera. Furthermore, 3-IAA gavage achieves similar effects. Mechanistic investigations confirm the transcriptional activation of COL1A1 by 3-IAA via promoting the enrichment of SP1 to its promoter. Together, our findings provide novel insights into the gut microbiota-eye axis in the pathogenesis of HM and propose new strategies for HM intervention by remodeling the gut microbiota and indole supplementation.

Abstract Image

肠道微生物群衍生的吲哚-3-乙酸通过促进 I 型胶原蛋白的合成抑制高度近视的发展。
高度近视(HM)是全球致盲的主要原因之一,目前尚无有效的干预措施。其主要障碍在于人们往往将其孤立地视为一种纯粹的眼部疾病,而忽视了其潜在的系统性影响。最近的证据表明存在肠道-眼睛轴;然而,肠道微生物群在 HM 发病机制中的作用在很大程度上仍未被探索。在此,我们提供了 HM 的肠道菌群失调、微生物代谢产物和巩膜重塑之间的潜在串联关系。通过 16S rRNA 基因测序,我们观察到 HM 患者的肠道微生物群谱发生了改变,与健康对照组相比,益生菌丰度显著降低。随后的靶向代谢谱分析显示,HM 患者的血浆中肠道微生物群衍生代谢物吲哚-3-乙酸(3-IAA)水平明显下降,这与益生菌的减少密切相关,两者均与 HM 的严重程度呈负相关。遗传分析表明,肠道微生物群与近视风险存在因果关系。重要的是,当 HM 模型小鼠接受来自健康捐赠者的粪便微生物群移植时,血浆中的 3-IAA 水平会增加,同时会延缓 HM 的发展,更好地维持巩膜中 I 型胶原蛋白α1(COL1A1)的表达。此外,灌胃 3-IAA 也能达到类似的效果。机理研究证实,3-IAA 通过促进 SP1 向其启动子富集而激活了 COL1A1 的转录。总之,我们的研究结果提供了有关 HM 发病机制中肠道微生物-眼睛轴的新见解,并提出了通过重塑肠道微生物群和补充吲哚来干预 HM 的新策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell Discovery
Cell Discovery Biochemistry, Genetics and Molecular Biology-Molecular Biology
CiteScore
24.20
自引率
0.60%
发文量
120
审稿时长
20 weeks
期刊介绍: Cell Discovery is a cutting-edge, open access journal published by Springer Nature in collaboration with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). Our aim is to provide a dynamic and accessible platform for scientists to showcase their exceptional original research. Cell Discovery covers a wide range of topics within the fields of molecular and cell biology. We eagerly publish results of great significance and that are of broad interest to the scientific community. With an international authorship and a focus on basic life sciences, our journal is a valued member of Springer Nature's prestigious Molecular Cell Biology journals. In summary, Cell Discovery offers a fresh approach to scholarly publishing, enabling scientists from around the world to share their exceptional findings in molecular and cell biology.
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