Article review: Gut Microbes May Trigger Non-infectious Uveitis. Written by Linda Roach et al.

Clinical update: EyeNet Magazine, July 2018. American Academy of Ophthalmology.

This was a very interesting article which describes how gut microbes may underlie autoimmune eye disease (non-infectious Uveitis) and how probiotics may have a role in the management.

“The microbes that live in our gut educate our immune system. Any diseases in which the immune system is involved are affected by the gut microbiome and that includes all non-infectious causes of uveitis,” said James T. Rosenbaum, MD, at Oregon Health & Science University in Portland.

The gastrointestinal mucosa is populated by bacteria, fungi, and viruses, which are estimated cumulatively to greatly outnumber cells in the human body. It is estimated that greater than 50% of immune systems antigen presentation occurs in our guts.

Balance in the gut flora is a complex process and disruption of this balance can lead to local inflammation (inflammatory bowel disease) as well as inflammation in distant sites like the eye. This dysregulation of the microbiome may also be linked to some forms of arthritis, atherosclerosis, diabetes and multiple sclerosis.

Dr Caspi (Head of the Immunoregulation Section and chief of the Laboratory of Immunology at the NEI in Bethesda) and her group performed a uveitis study in transgenic mice which develop spontaneous uveitis by the age of 2 months. The team found a high level of peripheral blood T cells with a receptor for specific eye protein (interphotoreceptor retinoid -binding protein). This protein in the eye should have been protected from the peripheral immune system by the eyes blood retinal barrier which usually provides the eye with immune privilege. Dr Caspi’s group demonstrated that the T lymphocyte cell response to the eye protein activated in the gut in response to a gut flora microbe which mimicked the eye protein. The activated effector T cells then passes through the intestine and migrate to the eye where they breakdown the blood retinal barrier and cause uveitis.

“When lymphocytes are activated, they will not stay in the bloodstream,” Dr. Caspi said. Instead, “they will immediately go to tissue, looking for their antigens.” Thus, she said, “we believe—and I have to emphasize that the experiments we’re doing now are trying to confirm this—that the lymphocytes migrate to the eye, break through the blood-retinal barrier, and initiate uveitis. In our current research, we’re trying to address the questions of how do they get out of the gut, where do they go, and how do they end up in the eye.”

There is a complex interplay between effector T cells who seek out antigen resulting in  inflammation and regulatory T cells who keep the effectors under check.

Dr. Lin (Assistant professor of ophthalmology at the Casey Eye Institute at Oregon Health & Science University in Portland) said her lab found that dietary supplementation with short-chain fatty acids—which normally form in the gut as fermentation metabolites of dietary fibre—dampens down uveitis in 2 ways: 1) The fatty acids increase regulatory T cells in the colon and in cervical lymph nodes, and 2) they reduce migration of effector T lymphocytes to the spleen.

Dr. Caspi’s group, in collaboration with scientists at the University of Cali­fornia at Berkeley, is exploring another potential route to modulating effector T lymphocytes via the lipid mediator lipoxin A4. Under healthy conditions, this endogenous bioactive molecule modulates adaptive immune responses to prevent chronic inflammation. When uveitic mice were treated with lipoxin A4, ocular inflammation was reduced.

Dr Rosenbaum said “We’re not at a point right now where we can say if you take a certain probiotic you’re going to be better, if you eat your broccoli and brussels sprouts you’re going to be better, or if you avoid chocolate you’re going to be better. We don’t know that yet. But we will.”

After reading this article it is clear that a more holistic approach is needed in the management of eye inflammation. I will be advising eating more fibre and perhaps the addition of probiotics. Watch this space.