Retinitis pigmentosa is associated with shifts in the gut microbiome

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.

Gut Microbiome in Retina Health: The Crucial Role of the Gut-Retina Axis

“…Another retinal disease influenced by the gut microbiome is the RP. Kutsyr et al (2021) have shown, in an experimental mouse model, that changes in gut microbiome composition are linked to RP. They observed some retinal degenerative abnormalities, such as deterioration of both retinal responsiveness to light stimuli and visual acuity, in animals with retinitis pigmentosa and with changes in gut microbiome.…”

“…On the contrary, affected mice were missing the most common genetic variants (Rikenella spp., Muribaculaceae spp., Prevotellaceae UCG-001 spp., and Bacilli spp.) typical of a healthy gut microbiome (Kutsyr et al, 2021). The link between gut microbiome changes and ocular diseases has been explained by several mechanisms (Nayyar et al, 2020).…”

“…All these hypotheses may also explain the neuroinflammation, oxidative stress and cell death registered in the mice model with retinitis pigmentosa. Furthermore, it can be hypothesized that different stages of retinal degeneration might be related to different changes in the gut microbiome (Kutsyr et al, 2021).…”

Neuroinflammation in retinitis pigmentosa: Therapies targeting the innate immune system

“…Using the rd10 RP mouse model, Kutsyr O. et al. ( 262 ) related alterations in the composition profiles of the gut microbiome to RP. Compared to healthy mice, the gut microbiome of rd10 mice had reduced ASV richness and α diversity.…”

Metabolomics in Retinal Diseases: An Update

“…For instance, a recently identified peripherin rare haplotype variant can cause impairments of photoreceptor outer segment renewal and phototransduction [140], which is closely linked with retinitis pigmentosa punctata albescens (RPA), a non-syndromic retinal degeneration. In addition to genetic factors, other factors are closely associated with pathogenesis of RP, including inflammation [141,142], oxidative stress [143], and gut microbiota [144]. To date, the treatment strategies of RP mainly include supplementation with vitamin A, prosthetics, or gene therapy, although these treatments are not without controversies and limitations.…”