Learn how gut dysbiosis affects systemic and ocular health

Are you familiar with gut dysbiosis and the associated gut-eye axis? In this month’s column, I discuss the importance of one’s gut microbiota, review recent research related to glaucoma, and I present plausible provider tips to share with patients.

Gut importance

Just as each patient is unique, so is their gut microbiota. This unique microbiota profile is made up of trillions of microorganisms (mainly dominated by Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes). Among other benefits, these help boost the immune system, protect against pathogens, and aid in crucial nutrient metabolism.¹

Also, this intestinal ecosystem is dynamic, changes over time, and may become imbalanced due to unhealthy (but potentially modifiable) lifestyle choices, such as low physical activity, dietary habits (especially ingesting high-fat and high-sugar foods), personal hygiene, oral antibiotic use, and cultural routines. That said, nonmodifiable factors, such as age, race, gender, and genetics^1-3 (e.g., inflammatory bowel disease, Type I diabetes), can also be implicated in an imbalanced intestinal ecosystem.

This dysbiosis, or imbalance among healthy bacteria and unhealthy bacteria,⁴ due to the factors noted, “may induce a systemic immune response, hematogenic spread, and even the translocation of microbes to distant sites,”² including the eye. This creates a negative gut-eye relationship, or axis.

Research related to glaucoma

Although “…the mechanisms involved in regulation of the gut-eye axis have not yet been completely clarified,”¹ this gut-glaucoma axis may involve three main factors: (1) systemic bacterial dissemination, (2) neuroinflammation, and (3) obesity.

1. Systemic bacterial dissemination. Intestinal overpopulation of Helicobacter pylori⁵ (H. pylori), Bacteroides and Prevotella,¹ due to “direct bacterial dissemination to the optic nerve and/or retina,”¹ leads to increased chronic, low-grade inflammation, and increased localized vasoactive/reactive oxygen species on the optic nerve and within the trabecular meshwork. As a result, this biochemical process potentially causes decreased perfusion and decreased out-flow, respectively.⁶ As a side note, interestingly, it has been suggested that treating H. pylori in glaucoma patients may be beneficial in stabilizing/improving VF testing and IOP reduction.^7-8 Also, oral overpopulation of H. pylori and Streptococci 16S rRNA have been observed in glaucoma patients,⁵ with the latter finding supporting the association between recent teeth loss and risk of developing glaucoma.⁹

2. Neuroinflammation. Related to this bacterial imbalance, which is diffused systemically by “leaky gut syndrome,”^3,6 is associated chronic inflammation. Specific to the optic nerve, such neuroinflammation has been suggested to be another underlying (although under-appreciated) contributing factor in the development and progression of glaucoma.¹⁰

3. Obesity. This may directly and indirectly affect both the development and progression of glaucoma. More specifically, “The conventional view assumes that the higher red cell aggregation, hematocrit, and hemoglobin levels in [overweight] people cause their blood to be more viscous. An increase in IOP may occur as a result of the increased resistance to the outflow of aqueous humor from the eye caused by the afflux reduction.”⁶ Obesity can induce vascular dysregulation and vasospasms of the arteries; and they participate in the distribution of blood flow to the optic nerve head, retina, and choroid.⁶ A decrease in blood flow to the optic nerve can make the nerves more vulnerable to harm from an IOP increase.⁶

“…Our review provides evi-dence that dysbiosis of the gut microbiome and related inflammation are shared pathological mechanisms involved in the development of obesity and glaucoma.”⁶

Provider Tips

Aside from collecting stool samples from glaucoma patients and fecal matter transplantation from healthy donors via “oral route or direct implantation using colonoscopy,”² the best recommendations we can pro-vide (and follow ourselves) are: Eat healthy,³ cut back on high-sugar/high-fat diets,¹ and develop an active lifestyle.⁶ Regarding food, this includes prebiotics² (fruits, vegetables, grains, and nuts¹¹) and probiotics² (yogurt, kombucha, tempeh, and kimchi). These foods help restore the normal microbiome environment.² Prebiotics and probiotics may help offset the associated systemic microbiota imbalance resulting from systemic antibiotic use.

One final thought: Since “…we are what we eat and the fact that the microbes are not passive partners in the gut [which] could positively influence human health…,”⁴ will restaurant menus soon include the microbe count and concentration of meal options? OM

References

1. Napolitano P, Filippelli M, Davinelli S, Bartollino S, dell’Omo R, Costagliola C. Influence of gut microbiota on eye diseases: an overview. Ann Med. 2021;53(1):750-761. doi: 10.1080/07853890.2021.1925150.
2. Gunardi TH, Susantono DP, Victor AA, Sitompul R. Atopobiosis and Dysbiosis in Ocular Diseases: Is Fecal Microbiota Transplant and Probiotics a Promising Solution? J Ophthalmic Vis Res. 2021;16(4):631-643. doi: 10.18502/jovr.v16i4.9754.
3. Medori MC, Naureen Z, Dhuli K, Placidi G, Falsini B, Bertelli M. Dietary supplements in retinal diseases, glaucoma, and other ocular conditions. J Prev Med Hyg. 2022;63(2 Suppl 3):E189-E199. doi: 10.15167/2421-4248/jpmh2022.63.2S3.2760.
4. Shivaji S. A systematic review of gut microbiome and ocular inflammatory diseases: Are they associated? Indian J Ophthalmol. 2021;69(3):535-542. doi: 10.4103/ijo.IJO_1362_20. Note: See Figure 1 for proposed overview of associated systemic and ocular complications of gut dysbiosis.
5. Baim AD, Movahedan A, Farooq AV, Skondra D. The microbiome and ophthalmic disease. Exp Biol Med (Maywood). 2019;244(6):419-429. doi: 10.1177/1535370218813616.
6. Pezzino S, Sofia M, Greco LP, Litrico G, Filippello G, Sarvà I, La Greca G, Latteri S. Microbiome Dysbiosis: A Pathological Mechanism at the Intersection of Obesity and Glaucoma. Int J Mol Sci. 2023;24(2):1166. doi: 10.3390/ijms24021166. Note: “When comparing patients with primary open-angle glaucoma (POAG) to healthy controls, Gong et al. discovered that the microbial composition of their guts varied: Prevotellaceae, Enterobacteriaceae, and Escherichia coli increased in abundance in POAG patients compared to healthy controls, whereas Megamonas and Bacteroides plebeius decreased significantly.” Additionally, this article has excellent graphs and figure summaries for review.)
7. Kountouras J., Mylopoulos N., Chatzopoulos D., et al. Eradication of Helicobacter Pylori May Be Beneficial in the Management of Chronic Open-Angle Glaucoma. Arch. Intern. Med. 2002;162:1237–1244. doi: 10.1001/archinte.162.11.1237.
8. Ala S., Maleki I., Sanjari Araghi AS, Sahebnasagh A, Shahraki A. Helicobacter Pylori Eradication in the Management of Glaucoma. Caspian J. Intern. Med. 2020;11(2):143–149. doi: 10.22088/cjim.11.2.143.
9. Pasquale LR, Hyman L, Wiggs JL, et al. Prospective Study of Oral Health and Risk of Primary Open-Angle Glaucoma in Men: Data from the Health Professionals Follow-up Study. Ophthalmology. 2016;123(11):2318-2327. doi: 10.1016/j.ophtha.2016.07.014.
10. Williams PA, Marsh-Armstrong N, Howell GR. Neuroinflammation in glaucoma: A new opportunity. Exp Eye Res. 2017;157:20-27. doi: 10.1016/j.exer.2017.02.014.
11. Cleveland Clinic. HealthEssentials. What Are Prebiotics and What Do They Do? Here’s why prebiotics matter. https://health.clevelandclinic.org/what-are-prebiotics/ (Accessed June 16, 2023.)

DR. LIFFERTH practices at Center for Sight. He is a member of the Optometric Glaucoma Society and a Glaucoma Diplomate of the American Academy of Optometry. For additional glaucoma cases, you can also follow Dr. Lifferth on his Instagram account: glaucomaqd. Disclosures: None. Email him at glaucomaqd@yahoo.com.