Liu Sijing, Liu Jiangman, Xiang Jiayan, Yan Ruyu, Li Senmao, Fan Qiwei, Lu Liyuan, Wu Jiaxin, Xue Yunxia, Fu Ting, Liu Jun, Li Zhijie
International Ocular Surface Research Center, Key Laboratory for Regenerative Medicine, Institute of Ophthalmology, Jinan University, Guangzhou, China; Department of Ophthalmology, The First Affiliated Hospital of Jinan University, Guangzhou, China.
International Ocular Surface Research Center, Key Laboratory for Regenerative Medicine, Institute of Ophthalmology, Jinan University, Guangzhou, China; Department of Pathology, School of Medicine, Jinan University, Guangzhou, China.
Am J Pathol. 2025 Apr;195(4):770-796. doi: 10.1016/j.ajpath.2024.11.010. Epub 2024 Dec 26.
The gut microbiota plays a crucial regulatory role in various physiological processes, yet its impact on corneal homeostasis remains insufficiently understood. Here, the effects of antibiotic-induced gut dysbiosis (AIGD) and germ-free conditions were investigated on circadian gene expression, barrier integrity, nerve density, and immune cell activity in the corneas of mice. Both AIGD and germ-free conditions significantly disrupted the overall transcriptomic profile and circadian transcriptomic oscillations in the cornea, as indicated by RNA sequencing. These molecular disturbances were accompanied by a reduction in corneal epithelial thickness, nerve density, corneal sensitivity, and compromised barrier function. Notably, supplementation with short-chain fatty acids (SCFAs) significantly restored corneal integrity in AIGD mice. Further single-cell sequencing revealed that SCFA receptors G-protein-coupled receptor 109A (Hcar2), olfactory receptor 78 (Olfr78), and G-protein-coupled receptor 43 (Ffar2) are expressed in corneal epithelial basal cells, embryonically derived macrophages, perivascular cells, and γδ T cells, respectively. In conclusion, this study demonstrated that the gut microbiota plays a critical role in corneal physiology by regulating circadian gene expression and maintaining barrier function. These findings enhance our understanding of the gut-eye axis, highlighting the cornea as a target for microbiota-derived metabolic signals and underlining the potential therapeutic value of SCFAs in treating corneal dysfunction.
肠道微生物群在各种生理过程中发挥着关键的调节作用，但其对角膜稳态的影响仍未得到充分了解。在此，研究了抗生素诱导的肠道菌群失调（AIGD）和无菌条件对小鼠角膜中昼夜节律基因表达、屏障完整性、神经密度和免疫细胞活性的影响。RNA测序表明，AIGD和无菌条件均显著破坏了角膜的整体转录组图谱和昼夜节律转录组振荡。这些分子紊乱伴随着角膜上皮厚度、神经密度、角膜敏感性的降低以及屏障功能受损。值得注意的是，补充短链脂肪酸（SCFAs）可显著恢复AIGD小鼠的角膜完整性。进一步的单细胞测序显示，SCFA受体G蛋白偶联受体109A（Hcar2）、嗅觉受体78（Olfr78）和G蛋白偶联受体43（Ffar2）分别在角膜上皮基底细胞、胚胎来源的巨噬细胞、血管周围细胞和γδT细胞中表达。总之，本研究表明肠道微生物群通过调节昼夜节律基因表达和维持屏障功能在角膜生理中起关键作用。这些发现加深了我们对肠-眼轴的理解，突出了角膜作为微生物群衍生代谢信号的靶点，并强调了SCFAs在治疗角膜功能障碍方面的潜在治疗价值。
