July 2018

NEWS & OPINION

Human microbiome research makes headway
but ocular microbiome research still emerging


by Vanessa Caceres EyeWorld Contributing Writer

Early findings point to possible role of microbiota in eye disease

Knowledge from the 2008 Human Microbiome Project has led to numerous clinical insights on the body’s microbial species and new treatments for systemic diseases. Yet have insights on microbial species helped improve care for eye diseases?
It’s early along the research pathway to say for sure, but the potential appears promising.

Human microbiome and systemic disease

Insights from the human microbiome and the trillions of bacteria, viruses, and fungi that are part of the human microbiota enhance understanding of various human diseases and their pathophysiologies, wrote Louise Lu and Ji Liu in “Human microbiota and ophthalmic disease.”1 “Discovery of various aspects of the human microbiota and its role in pathophysiology and pathogenesis has revolutionized our approach in studying certain diseases and developing novel treatment modalities,” they wrote.
The research in this area has led to specific systemic disease insights. “Evidence has indicated that altered gut microbiome can contribute to bowel disease, such as inflammatory bowel disease; autoimmune conditions, glycemic control related to diabetes, lipid metabolism related to cholesterol; and pain sensitization, which may be related to depression and anxiety, among other conditions,” said Ming Wang, MD, PhD, Wang Vision 3D Cataract & LASIK Center, Nashville, Tennessee.
“What has occurred in the last decade is the advent of culture-independent techniques to identify and quantify microbes in these complex communities,” said Lisa Park, MD, associate professor of ophthalmology, Columbia University Medical Center, New York. This includes the use of polymerase chain reaction to amplify genomic material from microbes that have been undetectable by traditional culture techniques and 16s ribosomal DNA sequencing, as well as computational tools that can analyze large data sets. “These techniques have allowed us to explore and characterize these microbial communities and begin to determine their relationship and contribution to overall health,” Dr. Park said.
The earliest studies in the human microbiome have related to gut health, and Dr. Park cited the treatment of Pseudomembranous colitis with fecal microbiota transplantation as a success in this area. “This is a clinical procedure that introduces stool from a healthy donor via colonoscopy or enema to restore healthy gut microbiota and combat potentially fatal Clostridium difficile infections,” she said.
Among the general population, a better understanding of the gut microbiome has led to the use of oral probiotic supplements or the consumption of probiotic-rich foods to return the gut to a healthy state, such as after antibiotic use for an infection. “There is still not conclusive evidence to how and when probiotics should be applied for newer applications,” Dr. Wang said. “We still do not know what strains are best for specific conditions. The lack of knowledge is a drawback for recommending their widespread use.” Still, they are generally thought of as safe except for minor side effects like gas and bloating.

Honing in on the eye

How does this background on the human microbiome set the stage for an ocular microbiome?
“Further investigation of the ocular surface microbiome, as well as the microbiome of other areas of the body such as the oral mucosa and gut, and their role in the pathophysiology of diseases is a significant, emerging field of research, and may someday enable the development of novel probiotic approaches for the treatment and prevention of ophthalmic diseases,” Drs. Lu and Liu wrote in their article.1
The research is slow to emerge, and most of it has centered on the characterization of the ocular biome, to determine if there are commonalities between the bacteria that live on a healthy cornea, Dr. Wang observed. “For the most part, this research has demonstrated that comparatively, there are much fewer types and number of bacteria on the ocular surface than other areas such as the skin or gut,” he said. “Also, the composition seems to appear much more variable between individuals than other areas of the body.”
One example related to this was an investigation of the conjunctiva of 45 healthy subjects who were sampled over 3 months and processed using culture-dependent and culture-independent methods.2 The study found a low diversity of microorganisms and no uniquely ocular taxa that occurred in all individuals. This may indicate that the ocular surface does not support a substantial core microbiome, Dr. Park said. “However, some individuals did demonstrate consistent species, suggesting the possibility of an individual-specific core microbiome,” she said.
Another study discovered that when Corynebacterium mastitidis was cultured with immune cells from the conjunctiva in mice, it induced the production of interleukin-17.3 When the mice were treated with an antibiotic to kill C. mast and challenged with Candida albicans, the mice receiving the antibiotics had a lower immune response and could not eliminate the C. albicans. This led to ocular infection. By contrast, the mice with normal C. mast could fend off the fungus.
“This result is an extremely interesting one that has far-reaching implications for future eye therapies,” Dr. Park said.
There also has been research focused on how contact lenses can alter the microbiome. “There is compelling evidence that those who wear contact lenses do have an alteration with more types and prevalence of bacteria than those who do not,” Dr. Wang said.
The effect of contact lenses is just one way that the ocular surface microbiome may be affected. “The ocular surface microbiome can be altered by a variety of mechanisms, such as environmental changes, pathological states that include dry eye syndrome, contact lens wear, keratoprosthesis, use of topical antibiotics, and infection,” said Rupa Shah, MD, ReVision LASIK & Cataract Surgery, Columbus, Ohio. “Clinically, this can present as contact lens-associated infiltrates, blepharitis, and postoperative infections such as endophthalmitis.”
There is even research that is connecting the microbiomes of other areas of the body to the pathophysiology of ophthalmic diseases, Dr. Shah said, giving the example of the oral microbiome and a link to glaucoma and the intestinal microbiome and uveitis.4,5

References

1. Lu LJ, Liu J. Human microbiota and ophthalmic disease. Yale J Biol Med. 2016;89:325–330.
2. Ozkan J, et al. Temporal stability and composition of the ocular surface microbiome. Sci Rep. 2017;7:9880.
3. St Leger AJ, et al. An ocular commensal protects against corneal infection by driving an interleukin-17 response from mucosal Ɣδ T cells. Immunity. 2017;47:148–158. 
4. Astafurov K, et al. Oral microbiome link to neurodegeneration in glaucoma. PloS One. 2014;9:e104416.
5. Rosenbaum JT, et al. The microbiome, HLA, and the pathogenesis of uveitis. Jpn J Ophthalmol. 2016;60:1–6.

Editors’ note: The physicians have no financial interests related to their comments.

Contact information

Park
: lisa.park@columbia.edu
Shah: rupas@revisioneyes.com
Wang: drwang@wangvisioninstitute.com

Human microbiome research makes headway but ocular microbiome research still emerging Human microbiome research makes headway but ocular microbiome research still emerging
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