The Eye of the Microbiome

Microbes

“If you don’t like bacteria, you’re on the wrong planet” – Stewart Brand

When we refer to our gut feelings, we seldom think of what exactly is going on in the gut. Over the past couple of years, studies have shown that our feelings in fact do have a lot to do with the residents of our gut. The gut microbiome consists of a community of microorganisms flourishing and thriving inside the gastrointestinal tract, or gut for short. These microorganisms not only influence our feelings, but also have a huge impact on our metabolism and well-being.

The Human Microbiome project was established in 2008 by the NIH (National Institute of Health) to gain a better understanding of the complex microbial genome. The microbiome project opened up a plethora of research opportunities based on the premise that microbiomes do not function as isolated units. A strong correlation was observed between our diet, microorganisms and disease pathology.

 The gastrointestinal tract consists of a huge network of commensal bacteria engaged in a symbiotic relationship with the host. For instance, the types of microbes residing in the gut have a very strong influence in regulating and maintaining our body’s immune responses. This brings up the question of, how the gut microflora would affect the incidence/progression of autoimmune diseases, considering it influences the immune system. Autoimmune diseases are disorders where the immune system becomes defective, and starts attacking the body’s own tissues/cells as a result. One of the mechanisms involved in autoimmune responses is molecular mimicry. Molecular mimicry refers to a phenomenon where foreign proteins (from microorganisms/pathogens) mimic self (the body’s own) proteins and mount an immune response against the body’s own tissues and cells. In other words, gut bacteria can mimic certain proteins and use the host’s own immune system to attack a particular tissue/organ in the body harboring that protein.

One such autoimmune disorder affecting the eye is Uveitis. Uveitis is an autoimmune-mediated, non-infectious disease influenced by various genetic and environmental factors. The autoimmune responses in uveitis are triggered by T cells (T cells are a type of lymphocyte) which break through the blood-ocular barrier. The human eye is considered as an immune privileged site (able to tolerate foreign antigens without eliciting an inflammatory response) with a blood-ocular barrier, which regulates the exchange of nutrients and cells between various tissues and eye. It is also imperative to understand that the term immune privilege does not mean an all-or-none response. It rather refers to regulation of the immune response in an attempt to prevent exacerbated autoimmune diseases.

T cells normally respond to proteins or surface markers expressed on bacteria, fungi or cells and become activated. The T cells inducing an autoimmune response in uveitis are activated in response to retinal antigens. These retinal antigens are sequestered within the immune privileged eye. The paradox lies in the fact that the T cells must be activated in order to breach the blood-ocular barrier and the impetus driving their activation lies beyond the barrier. Therefore, it is possible that there is a secretory protein or stimulus that mimics the retinal antigens in an entirely different tissue like the gut.

Using a mouse model of experimental uveitis known as the EAU (Experimental autoimmune uveitis) model, scientists have identified a large number of activated T cells that reside in the guts/intestines of these mice, even before the disease symptoms become prominent. The gut microflora in these mice mimicked the retinal antigens and activated the T cells. Once T cells were activated, they breached the blood-ocular barrier to enter the eye. Once inside the eye, they initiated an autoimmune response against the body’s own retinal antigens resulting in the pathogenesis of uveitis.

In an attempt to alter the bacteria in the gut, these mice were orally treated with a cocktail of antibiotics. The idea behind the antibiotic treatment was to eliminate the gut bacteria and subsequently their secretory products that mimic the retinal antigens. The mice with the antibiotic treatment developed the disease at a much later time point with less severity as compared to the untreated control group. These results reiterate the importance of maintaining the gut microflora and its influence on disease pathology.

The gastrointestinal tract harbors an exorbitant number of microbes (trillions) which explains why they influence our overall well-being.  The coexistence of humans and microbes is a quintessential example of the Yin and Yang theory. As much as we want to get rid of the bad bacteria, we need to balance it with preserving the good bacteria. We also need to watch what we eat because this has a direct impact on our microbiome. The gut has the guts to modify our immune system, so it’s best to keep an eye on what we feed it.

 For more related articles on this topic : The Microbiome: Our Gut Feeling

Image credit: devourilm

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