Retinitis pigmentosa is associated with shifts in the gut microbiome

Oksana Kutsyr,Pedro Lax,Nicolás Cuenca,Mónica Lluesma-Gomez,Lucía Maestre-Carballa,Manuel Martinez-Garcia

doi:10.1038/s41598-021-86052-1

Abstract

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.

Highlights

The gut microbiome is known to influence the pathogenesis and progression of neurodegenerative diseases
In rd[10] mice, maximum amplitudes observed for scotopic a- and b-waves were 12% and 34% of the values obtained in C57BL/6J mice (Fig. 1b,c)
The outer nuclear layer (ONL) thickness in rd[10] mice was 31% of the values obtained in C57BL/6J mice (18.6 ± 1.6 vs. 60.4 ± 2.0 μm)

Summary

Introduction

The gut microbiome is known to influence the pathogenesis and progression of neurodegenerative diseases. In rd[10] 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. The retina reflects some of the pathological alterations of many neurodegenerative diseases and may provide information of brain pathology s everity[31,32] In this context, a few recent studies have linked gut microbiome changes with some retinal degenerative d iseases[33,34], including age-related macular degeneration (AMD)35–39, glaucoma[40,41,42,43] and diabetic retinopathy[44], even though the published results vary depending on the type and stage of the disease and between studies. Time courses of photoreceptor cell death and subsequent retinal degeneration in rd[10] mice closely resembles the human disease p rocess[30,57]

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Discussion

Conclusion