Dysbiosis of gut microbiome contributes to glaucoma pathogenesis

Abstract

Microbiome dysfunction is considered to contribute to the pathogenesis of many neurodegenerative diseases. However, the relationship between the gut microbiome and glaucoma, a neurodegenerative disorder remains largely unknown. Here, we identified that the gut microbiome of glaucoma patients were rich in Dysgonamonadaceae, along with a lower level of Barnesiellaceae by metagenomic sequencing. This microbiome pattern is shown to increased the production of short chain fatty acids (SCFAs) in the fecal and blood samples. Reducing these glaucoma-specific gut microbiome bacteria significantly reduced retinal ganglion cell (RGC) loss by alleviating the activation of retinal microglia cells and overproduction of inflammatory cytokines in acute glaucoma mouse model, whereas SCFAs treatment aggravated microglia activation. Mechanistically, reducing the glaucoma-specific gut microbiome bacteria decreased the retinal microRNA profile including MiR-122-5p, which led to neuroprotection through inhibition of retinal inflammation. We validated our results by showing that fecal microbiome transplantation from glaucoma patients significantly exacerbated retinal microglia activation and increased retinal inflammation. Our findings indicate that the change of gut MedComm -Future Medicine. 2022;e28.wileyonlinelibrary.com/journal/mef2

Effect of the gut microbiome in glaucoma risk from the causal perspective

“… 31 However, recent research suggests a potential link between SCFAs and the development of glaucoma. Our discoveries align with previous studies, 12 suggesting the involvement of the gut microbiome in glaucoma pathogenesis. Their research highlights that administering intestinally metabolised SCFAs exacerbated retinal cell loss.…”

“…Despite the fact that observational studies have suggested the potential importance of the gut-retina axis in the pathogenesis of glaucoma, 12 13 the exact causal relationship between GM and glaucoma risk remains uncertain. In this study, we conducted a bidirectional two-sample MR analysis to explore this relationship.…”

“…A growing body of evidence highlights the significant link between GM dysbiosis and a variety of ocular diseases6 8–10 and neurodegenerative conditions 11. Notably, observational studies have shown variations in the bacterial composition of individuals with glaucoma, and intriguingly, transplantation of glaucoma-associated faecal microbiota into mice has been shown to activate microglial cells and induce retinal inflammation, suggesting an underlying gut-retina axis in disease pathogenesis 12. Another study demonstrated the significant role of gut-homing β7 + CD4 + T cells in retinal ganglion cell damage in glaucoma in both human and mouse models 13 14.…”

“… 11 Notably, observational studies have shown variations in the bacterial composition of individuals with glaucoma, and intriguingly, transplantation of glaucoma-associated faecal microbiota into mice has been shown to activate microglial cells and induce retinal inflammation, suggesting an underlying gut-retina axis in disease pathogenesis. 12 Another study demonstrated the significant role of gut-homing β7 + CD4 + T cells in retinal ganglion cell damage in glaucoma in both human and mouse models. 13 14 This finding highlights the complex interplay of the gut-retina axis in the pathophysiology of glaucoma.…”

Gender Influences Gut Microbiota among Patients with Irritable Bowel Syndrome

“…IBS is often diagnosed in patients who have undergone gastroenteritis in the past [ 12 ]. At the same time, other studies indicated that intestinal dysbiosis is the cause of the disease, resulting from abnormalities in the quantitative and qualitative composition of the gut microbiota [ 13 , 14 , 15 ], which were previously assessed based on data obtained using 16S rRNA gene phylogenetic microarray analysis [ 16 ] or real-time PCR techniques [ 17 ]. It is still not known whether intestinal diseases result directly from the dysbiosis of the intestinal microflora or are a consequence of other factors that can affect the intestinal microflora.…”