Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization.
Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization.
复制标题
DOI：
10.15252/emmm.201606531
复制
发表时间：
2016-12
影响因子：
11.1
通讯作者：
Sapieha P
中科院分区：
文献类型：
--
作者：
Andriessen EM;Wilson AM;Mawambo G;Dejda A;Miloudi K;Sennlaub F;Sapieha P
新生血管形式的年龄相关性黄斑变性 (NV AMD) 是 60 岁以上成年人视力丧失的主要原因。流行病学数据表明，在男性中，总体腹部肥胖是继吸烟之后进展为晚期 NV AMD 的第二个最重要的环境危险因素。迄今为止，强调这一观察结果的机制仍然不明确。鉴于高脂肪饮食对肠道微生物群的影响，我们研究了共生微生物是否影响 AMD 的进化。使用 NV AMD 小鼠模型、微生物移植和其他改变肠道微生物群的范例，我们将体重增加与混杂因素分开，并证明高脂肪饮食通过改变肠道微生物群而加剧脉络膜新生血管（CNV）。肠道菌群失调导致肠道通透性升高和慢性低度炎症，炎症特征是 IL-6、IL-1β、TNF-α 和 VEGF-A 的产生增加，最终加剧病理性血管生成。
Age‐related macular degeneration in its neovascular form (NV AMD) is the leading cause of vision loss among adults above the age of 60. Epidemiological data suggest that in men, overall abdominal obesity is the second most important environmental risk factor after smoking for progression to late‐stage NV AMD. To date, the mechanisms that underscore this observation remain ill‐defined. Given the impact of high‐fat diets on gut microbiota, we investigated whether commensal microbes influence the evolution of AMD. Using mouse models of NV AMD, microbiotal transplants, and other paradigms that modify the gut microbiome, we uncoupled weight gain from confounding factors and demonstrate that high‐fat diets exacerbate choroidal neovascularization (CNV) by altering gut microbiota. Gut dysbiosis leads to heightened intestinal permeability and chronic low‐grade inflammation characteristic of inflammaging with elevated production of IL‐6, IL‐1β, TNF‐α, and VEGF‐A that ultimately aggravate pathological angiogenesis.