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长期高果糖摄入通过诱导小鼠肠道菌群失调促进泪腺功能障碍。

Long-term high fructose intake promotes lacrimal gland dysfunction by inducing gut dysbiosis in mice.

机构信息

Henan Eye Institute, Henan Eye Hospital and Henan Key Laboratory of Ophthalmology and Visual Science, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, 450000, China.

Henan Eye Institute, Henan Eye Hospital and Henan Key Laboratory of Ophthalmology and Visual Science, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, 450000, China.

出版信息

Exp Eye Res. 2023 Sep;234:109573. doi: 10.1016/j.exer.2023.109573. Epub 2023 Jul 11.

DOI:10.1016/j.exer.2023.109573
PMID:37442219
Abstract

The lacrimal gland is essential for maintaining ocular surface health through the secretion of the aqueous layer of the tear film. It is therefore important to explore the intrinsic and extrinsic factors that affect the structure and function of the lacrimal gland and the mechanisms underlying them. With the prevalence of Westernized diets characterized by high sugar and fat content, the susceptibility to many diseases, including ocular diseases, is increased by inducing dysbiosis of the gut microbiome. Here, we found that the composition, abundance, and diversity of the gut microbiome was significantly altered in mice by drinking 15% high fructose water for one month, as determined by 16S rRNA sequencing. This was accompanied by a significant increase in lipid deposition and inflammatory cell infiltration in the extraorbital lacrimal glands (ELGs) of mice. Transcriptome analysis based on bulk RNA-sequencing revealed abnormal activation of some of several metabolic and immune-related pathways. In addition, the secretory response to stimulation with the cholinergic receptor agonist pilocarpine was significantly reduced. However, when the composition and diversity of the gut microbiome of high fructose intake (HFI)-treated mice were improved by transplanting feces from normal young healthy mice, the pathological alterations in ELG structure, inflammatory cell infiltration, secretory function and transcriptome analysis described above were significantly reversed compared to age-matched control mice. In conclusion, our data suggest that prolonged HFI may cause pathological damage to the structure and function of the ELG through the induction of gut dysbiosis. Restoration of intestinal dysbiosis in HFI-treated mice by fecal transplantation has a potential role in ameliorating these pathological impairments.

摘要

泪腺通过分泌泪膜的水层来维持眼表健康,因此探索影响泪腺结构和功能的内在和外在因素及其机制非常重要。随着高糖和高脂肪含量的西式饮食的流行,肠道微生物组的失调会增加许多疾病的易感性,包括眼部疾病。在这里,我们发现通过让小鼠饮用 15%的高果糖水一个月,用 16S rRNA 测序可以确定其肠道微生物组的组成、丰度和多样性发生了显著改变。这伴随着眶外泪腺(ELG)中脂质沉积和炎性细胞浸润的显著增加。基于 bulk RNA-seq 的转录组分析显示,一些代谢和免疫相关途径的异常激活。此外,对胆碱能受体激动剂毛果芸香碱刺激的分泌反应显著降低。然而,当通过移植来自正常年轻健康小鼠的粪便来改善高果糖摄入(HFI)处理小鼠的肠道微生物组的组成和多样性时,与年龄匹配的对照小鼠相比,上述 ELG 结构、炎性细胞浸润、分泌功能和转录组分析的病理改变得到了显著逆转。总之,我们的数据表明,长期 HFI 通过诱导肠道菌群失调可能导致 ELG 的结构和功能发生病理损伤。通过粪便移植恢复 HFI 处理小鼠的肠道菌群失调可能在改善这些病理损伤方面发挥作用。

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