Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
Institute Ramón Margalef, University of Alicante, Alicante, Spain.
Sci Rep. 2021 Mar 23;11(1):6692. doi: 10.1038/s41598-021-86052-1.
The gut microbiome is known to influence the pathogenesis and progression of neurodegenerative diseases. However, there has been relatively little focus upon the implications of the gut microbiome in retinal diseases such as retinitis pigmentosa (RP). Here, we investigated changes in gut microbiome composition linked to RP, by assessing both retinal degeneration and gut microbiome in the rd10 mouse model of RP as compared to control C57BL/6J mice. In rd10 mice, retinal responsiveness to flashlight stimuli and visual acuity were deteriorated with respect to observed in age-matched control mice. This functional decline in dystrophic animals was accompanied by photoreceptor loss, morphologic anomalies in photoreceptor cells and retinal reactive gliosis. Furthermore, 16S rRNA gene amplicon sequencing data showed a microbial gut dysbiosis with differences in alpha and beta diversity at the genera, species and amplicon sequence variants (ASV) levels between dystrophic and control mice. Remarkably, four fairly common ASV in healthy gut microbiome belonging to Rikenella spp., Muribaculaceace spp., Prevotellaceae UCG-001 spp., and Bacilli spp. were absent in the gut microbiome of retinal disease mice, while Bacteroides caecimuris was significantly enriched in mice with RP. The results indicate that retinal degenerative changes in RP are linked to relevant gut microbiome changes. The findings suggest that microbiome shifting could be considered as potential biomarker and therapeutic target for retinal degenerative diseases.
肠道微生物组被认为会影响神经退行性疾病的发病机制和进展。然而，人们相对较少关注肠道微生物组在视网膜疾病（如色素性视网膜炎）中的影响。在这里，我们通过评估 rd10 色素性视网膜炎小鼠模型与对照 C57BL/6J 小鼠的视网膜变性和肠道微生物组，研究了与色素性视网膜炎相关的肠道微生物组组成的变化。在 rd10 小鼠中，与同龄对照小鼠相比，视网膜对闪光灯刺激的反应性和视力均恶化。在营养不良的动物中，这种功能下降伴随着光感受器的丧失、光感受器细胞的形态异常和视网膜反应性神经胶质增生。此外，16S rRNA 基因扩增子测序数据显示，微生物肠道菌群失调，在属、种和扩增子序列变异（ASV）水平上，营养不良和对照小鼠的α多样性和β多样性存在差异。值得注意的是，四种在健康肠道微生物组中相当常见的 ASV，即 Rikenella spp.、Muribaculaceae spp.、Prevotellaceae UCG-001 spp. 和 Bacilli spp.，在视网膜疾病小鼠的肠道微生物组中缺失，而 Bacteroides caecimuris 在患有色素性视网膜炎的小鼠中显著富集。结果表明，RP 中的视网膜退行性变化与相关的肠道微生物组变化有关。这些发现表明，微生物组的转移可以被认为是视网膜退行性疾病的潜在生物标志物和治疗靶点。
