High‐fat consumption alters the gut microbiome in retinitis pigmentosa mice and accelerates retinal degeneration

Purpose Intestinal dysbiosis has been linked with the pathogenesis of several degenerative diseases. Moreover, the consumption of high‐fat diets (HFD) can drove to significant changes in the gut microbiome. Our purpose was to investigate changes in gut microbiome and retinal degeneration associated with the ingestion of HFD in a mice model of retinitis pigmentosa (RP). Methods C57BL/6J mice and rd10 mice were fed either with normal chow (5.5% fat kcal) or with a HFD (61.6% fat kcal) for two weeks since P19. Retinal function was analyzed by electroretinography and optomotor test. Immunohistochemistry was employed to evaluate the structure and integrity of the retinal tissue. 16S rRNA gene sequencing was made to evaluate the gut microbiome. Results We found a higher retinal degeneration in rd10 mice as compared to C57BL/6J mice, both fed with normal chow. Rd10 mice exhibited significantly reduced retinal responsiveness, as well as diminished visual acuity. This loss of retina function went with a decrease in the number of photoreceptor rows, and the remaining photoreceptors showed morphologic anomalies. The photoreceptor degeneration was accompanied by an inflammatory response of the retina, characterized by the proliferation of microglial cells and reactive gliosis of Müller cells. Likewise, the gut microbiome analysis revealed differences in alpha and beta diversity at the genera, species, and amplicon sequence variants levels. HFD generated a significant dysbiosis in the gut microbiome increasing potentially pro‐inflammatory bacteria as Bilophila sp., Alistipes sp. and Mucispirillum schaedleri, and drived the exacerbation of the retinal degeneration. Conclusions In retinitis pigmentosa, retinal dysfunction and degeneration are related to significant changes in the gut microbiome, which can be altered by diet, conducing to a worsening of the disease. Support MINECOFEDER‐BFU2015‐67139‐R, FEDER‐PID2019‐106230RB‐I00, RETICS‐FEDER RD16/0008/0016, IDIFEDER/2017/064.