The correlation between primary open-angle glaucoma (POAG) and gut microbiota: a pilot study towards predictive, preventive, and personalized medicine

Chen, Si; Wang, Nan; Xiong, Siqi; Xia, Xiaobo

doi:10.1007/s13167-023-00336-2

Cited by 12 publications

(5 citation statements)

References 78 publications

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“… 47 – 49 Chen et al identified NF-κB subunit 1 (NFKB1) as one of the hub genes in glaucoma that are gut microbiome-related. 50 These hub genes may affect glaucoma progression through several metabolites, including butyrate. Schulthess et al demonstrated that butyrate can imprint potent antimicrobial activity during macrophage differentiation.…”

Section: Discussionmentioning

confidence: 99%

Glaucoma Patients Have a Lower Abundance of Butyrate-Producing Taxa in the Gut

Vergroesen,

Jarrar,

Weiss

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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Purpose Glaucoma is an eye disease that is the most common cause of irreversible blindness worldwide. It has been suggested that gut microbiota can produce reactive oxygen species and pro-inflammatory cytokines that may travel from the gastric mucosa to distal sites, for example, the optic nerve head or trabecular meshwork. There is evidence for a gut-eye axis, as microbial dysbiosis has been associated with retinal diseases. We investigated the microbial composition in patients with glaucoma and healthy controls. Moreover, we analyzed the association of the gut microbiome with intraocular pressure (IOP; risk factor of glaucoma) and vertical cup-to-disc ratio (VCDR; quantifying glaucoma severity). Methods The discovery analyses included participants of the Rotterdam Study and the Erasmus Glaucoma Cohort. A total of 225 patients with glaucoma and 1247 age- and sex-matched participants without glaucoma were included in our analyses. Stool samples were used to generate 16S rRNA gene profiles. We assessed associations with 233 genera and species. We used data from the TwinsUK and the Study of Health in Pomerania (SHIP) to replicate our findings. Results Several butyrate-producing taxa (e.g. Butyrivibrio , Caproiciproducens , Clostridium sensu stricto 1 , Coprococcus 1 , Ruminococcaceae UCG 007 , and Shuttleworthia ) were less abundant in people with glaucoma compared to healthy controls. The same taxa were also associated with lower IOP and smaller VCDR. The replication analyses confirmed the findings from the discovery analyses. Conclusions Large human studies exploring the link between the gut microbiome and glaucoma are lacking. Our results suggest that microbial dysbiosis plays a role in the pathophysiology of glaucoma.

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Section: Discussionmentioning

confidence: 99%

Glaucoma Patients Have a Lower Abundance of Butyrate-Producing Taxa in the Gut

Vergroesen,

Jarrar,

Weiss

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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“…Glaucoma, a prevalent and irreversible vision-impairing condition, is characterized by the gradual decline of retinal ganglion cells and their axons [ 1 , 2 ], resulting in narrowing of the visual field [ 3 ]. Over the past decade, there has been an increasing focus on exploring the connection between microbiota and glaucoma [ 5 , 6 , 42 , 43 ]. Microbiota imbalance (dysbiosis) triggered by various glaucoma risk factors, including aging [ 44 ], obesity [ 45 ], and depression [ 46 ], can lead to disruptions in metabolic, immune, and inflammatory processes.…”

Section: Discussionmentioning

confidence: 99%

“…Glaucoma can be divided into several subtypes, including primary open-angle glaucoma (POAG), primary angle-closure glaucoma (PACG), and secondary glaucoma. In POAG, serious damage may be caused to the optic nerve and the trabecular meshwork, which is the main pathway for drainage of aqueous humor and whose dysfunction leads to intraocular pressure (IOP) elevation [ 6 ]. The most common form of secondary glaucoma is pseudoexfoliation glaucoma (PEXG), caused by the deposition of fibrillar protein aggregates (PEX fibrils) on the anterior and posterior eye tissues [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Ocular Surface Microbiome and Tear Proteome in Glaucoma

Spörri,

Uldry,

Kreuzer

et al. 2024

IJMS

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Although glaucoma is a leading cause of irreversible blindness worldwide, its pathogenesis is incompletely understood, and intraocular pressure (IOP) is the only modifiable risk factor to target the disease. Several associations between the gut microbiome and glaucoma, including the IOP, have been suggested. There is growing evidence that interactions between microbes on the ocular surface, termed the ocular surface microbiome (OSM), and tear proteins, collectively called the tear proteome, may also play a role in ocular diseases such as glaucoma. This study aimed to find characteristic features of the OSM and tear proteins in patients with glaucoma. The whole-metagenome shotgun sequencing of 32 conjunctival swabs identified Actinobacteria, Firmicutes, and Proteobacteria as the dominant phyla in the cohort. The species Corynebacterium mastitidis was only found in healthy controls, and their conjunctival microbiomes may be enriched in genes of the phospholipase pathway compared to glaucoma patients. Despite these minor differences in the OSM, patients showed an enrichment of many tear proteins associated with the immune system compared to controls. In contrast to the OSM, this emphasizes the role of the proteome, with a potential involvement of immunological processes in glaucoma. These findings may contribute to the design of new therapeutic approaches targeting glaucoma and other associated diseases.

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“…Specifically, NLRP3 inflammasome activity was upregulated in the retina of glaucomatous DBA/2J mice [124]. TLR9 mRNA expression was significantly increased in trabecular meshwork from patients with POAG and in vitro TM culture systems [125]. In addition, cGAS-STING activity was increased in RGCs following ischemia/reperfusion and in poly(dA:dT)-treated BV-2 microglial cells [126].…”

Section: Role Of Aibp In Mitochondrial Dynamics and Function In Glauc...mentioning

confidence: 97%

AIBP: A New Safeguard against Glaucomatous Neuroinflammation

Choi,

Bastola

et al. 2024

Cells

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Glaucoma is a group of ocular diseases that cause irreversible blindness. It is characterized by multifactorial degeneration of the optic nerve axons and retinal ganglion cells (RGCs), resulting in the loss of vision. Major components of glaucoma pathogenesis include glia-driven neuroinflammation and impairment of mitochondrial dynamics and bioenergetics, leading to retinal neurodegeneration. In this review article, we summarize current evidence for the emerging role of apolipoprotein A-I binding protein (AIBP) as an important anti-inflammatory and neuroprotective factor in the retina. Due to its association with toll-like receptor 4 (TLR4), extracellular AIBP selectively removes excess cholesterol from the plasma membrane of inflammatory and activated cells. This results in the reduced expression of TLR4-associated, cholesterol-rich lipid rafts and the inhibition of downstream inflammatory signaling. Intracellular AIBP is localized to mitochondria and modulates mitophagy through the ubiquitination of mitofusins 1 and 2. Importantly, elevated intraocular pressure induces AIBP deficiency in mouse models and in human glaucomatous retina. AIBP deficiency leads to the activation of TLR4 in Müller glia, triggering mitochondrial dysfunction in both RGCs and Müller glia, and compromising visual function in a mouse model. Conversely, restoring AIBP expression in the retina reduces neuroinflammation, prevents RGCs death, and protects visual function. These results provide new insight into the mechanism of AIBP function in the retina and suggest a therapeutic potential for restoring retinal AIBP expression in the treatment of glaucoma.

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The correlation between primary open-angle glaucoma (POAG) and gut microbiota: a pilot study towards predictive, preventive, and personalized medicine

Cited by 12 publications

References 78 publications

Glaucoma Patients Have a Lower Abundance of Butyrate-Producing Taxa in the Gut

Glaucoma Patients Have a Lower Abundance of Butyrate-Producing Taxa in the Gut

Exploring the Ocular Surface Microbiome and Tear Proteome in Glaucoma

AIBP: A New Safeguard against Glaucomatous Neuroinflammation

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