RHR: The Ocular Microbiome, with Dr. Harvey Fishman

In this episode we discuss:

• What is the ocular microbiome?
• How the microbiome affects eye diseases
• T cell activation in the eye
• HLA-B27 and genes that play an important role in immune function
• A nutrient-dense and anti-inflammatory diet for eye health
• Antibiotics prior to surgery

Show notes:

• Dr. Harvey Fishman's website: fishmanvision.com

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Chris Kresser: Dr. Fishman, welcome to Revolution Health Radio. I'm so happy you could join us. I've really been looking forward to this.

Dr Harvey Fishman: Thank you so much for having me, Chris. This is wonderful.

What is the ocular microbiome?

Chris Kresser: So, my audience has been well aware of the gut microbiome for many years. We've also talked about the skin microbiome. We talked about the vaginal microbiome, the lung microbiome, more recently the nasal microbiology, and so it's not surprising to learn that there is also an ocular microbiome. I'm really looking forward to talking to you more about this and how it contributes to eye disease. Because in the conventional world, the options for preventing eye disease in the first place and then addressing them, I think, have come a long way but maybe still leaves something to be desired. I'd first love to start out with just hearing a little bit more about your background, how you became interested in the ocular microbiome in your work as an ophthalmologist, and what led you down this path.

Dr. Fishman: That's great. So, I have a pretty interesting background, where I started off in the world as a physical chemist, studied neuroscience. I was in an analytical chemistry microfluidic laser lab at Stanford and really got interested in how to measure molecules almost at the single molecule level. We were looking at vesicular and synaptic release, neurotransmitters, and what the chemical basis of learning and memory was.

 You’ve heard of the gut microbiome—and maybe even the skin, nasal, and vaginal microbiome. But did you know that the eyes also have a microbiome and that it plays a key role in ocular health? 

That was sort of my background, and then I sort of did some interesting work in neurobiology, looking at retinal cells and how they grow and their regeneration, so I've had a lot of sort of technical background and analytical chemistry background. And then the last couple of years, I started getting very interested in the microbiome of the intestine and the gut, which led me into this whole world of what is actually happening in the eyes. Is there an ocular microbiome and is there a biome that controls disease in the eye that similar to that in the gut?

What's interesting is that I didn't necessarily sort of think about it in those ways. I actually got into my research that I'm working on right now is we're actually looking at how to measure cancer on the eye. We're using some of the analytical techniques that I developed or had been working on for my whole sort of academic career, which is how do you measure very small amounts of materials in microenvironments, and so I naturally led to this concept of how do you measure cancers on the eye. We started using similar techniques and sort of the illumina high throughput sequencing technology using 16S rDNA and rRNA to look at different things on the cancer. Chris has led me right into how they are looking at the microbiome and that’s sort of what got my interest sparked. The other thing that's sort of interesting is I've been working with a company called Microbiome to do some studies where I'm actually looking at intestinal microbiomes and how that compares to disease in the eye. That's sort of a whirlwind tour of how I got interested.

Chris Kresser: Right. It's a fascinating background, and as is often the case, it seems like in some way you could have never designed this career path or predicted it would happen, but when you look at it in retrospect, it seems like each step kind of perfectly informed the next step.

Dr. Fishman: That’s right. It’s actually really interesting; I never in my wildest dreams would have thought that I'd be doing genomics, and in fact one of my previous advisers always laughs because I'm doing genomics and I was a physical chemist and a microanalytical guy.

Chris Kresser: Right, right.

Dr. Fishman: Whippersnapper.

Chris Kresser: Right. So let’s talk a little bit about the ocular microbiome and what we know about it so far and what we don't know about it. Do we have any sense of the number of species, microorganisms, what the functions of the ocular microbiome are? I imagine it's significantly less developed as a field of study than the gut microbiome, but what do we know so far?

Dr. Fishman: It's really the beginning of this field. What's interesting about the microbiome of the eye is that we've been interested in, as ophthalmologists, not me personally, but at the ophthalmology community, we've been very interested in the bacteria that lived on the eye. The reason is that most of our intraocular surgeries like cataract surgery, vitreoretinal surgery, corneal surgery, when you make incisions into the eye, most of the serious infections that occur, occur because the exogeneous either bacteria that live on the lashes, the eyelid margin, or in the cornea. And so we've been very interested in this for years, and they've done a lot of interesting work, but the concept of the ocular microbiome, whether there's like some low-level core bacteria and microbiological species that lives on, in, and around the eye, that's really kind of a new concept.

One of the papers that has come out just recently was actually by Mark Wilcox. I don’t know if you're familiar with it; it was a major paper in 2017, and they looked at basically the temporal stability and composition of the ocular surface microbiome. It was probably one of the best papers, if not the sentinel paper in the field. What they found is … well, there's a couple of things they found, that first of all the ocular biome is very different, if at all, than the microbiome of the intestine. One of the things that they found is that in addition to other work that's been done, is that it's actually a pretty low number of species. I mean, there’s a diverse number of species, but it’s a low number. It’s just a regular number. And then there was some work that was done by Russell Van Gelder who's also shown similar work, but basically they started to talk about a bacteria microbiome that’s just very small in number.

Chris Kresser:  It's interesting; there is some parallel too with the gut. For most of the 20th century, we were very well aware of the existence of pathogenic bacteria, parasites and other organisms that could cause dysfunction in the gut, and most of the focus there was on identifying those pathogens and then treating the disease, eradicating them if possible with antibiotics or treating the diseases that were caused by them, whereas now at least, the awareness has shifted, and to some extent toward how do we support and nourish the protective microbiome and look at it more in the context of an ecosystem where we understand that if the health of the ecosystem is the primary focus, then that may actually be the most effective way of protecting against pathogenic activity.

Do you think that something similar is going to happen with the ocular microbiome or that it's just too— because it's not as significant in terms of the volume of the number of organisms and we may not have as much ability to influence it with things like diet and lifestyle, we’re not going to go down a similar path there?

How the microbiome affects eye diseases

Dr. Fishman: It’s a great question, and that's really what a lot of … myself and many other people are working on—whether you can influence it. I have some anecdotal discussions on that, papers as well, that actually would suggest that you may be able to do the exact same thing for the ocular health as you do for the gut health. Let me give you a couple examples. There are some really significant diseases of the eye, like, for example, dry eye disease, which is actually an area that I'm super interested in and really focusing a lot of my academic and clinical research. Dry eye disease is … they think there's a very big component of how the ocular microbiome interacts with the cornea and the lid and so forth, but there are also a bunch of other diseases like episcleritis, chronic follicular conjunctivitis, pterygium, or surfer’s eye, scleritis, even things that are as interesting as macular degeneration and glaucoma, a lot of people are starting to have … some of these diseases are actually idiopathic, not macular degeneration necessarily, but like episcleritis and dry eye disease. There are these so-called idiopathic diseases. What we think is that it's really controlled by dysbiosis of microbiome.

Chris Kresser: Wow, that's interesting. For listeners, idiopathic means “we don't really know.” It's a fancy way of saying, “We don’t know where this comes from or how it starts.” It's fascinating and by now not surprising, given what we talked about at the beginning of the show, we know now about the microbiome is not just in the gut. There's microbiology and virtually in any surface that interacts with the exterior world, whether it's the gut, the inside of the gut, technically is outside the body. We've talked about that on the show, which is always kind of fascinating, especially if you haven't thought about that, and then the lungs, which of course interface with the exterior environment, and the skin, the vagina, there's a penis microbiome, and clearly these organisms are playing some important role and clearly there's something about the modern lifestyle that is antithetical to the health of microbiomes. I imagine with the ocular microbiome, is it influenced by the same factors? Does systemic antibiotic use contribute to a degradation of the quality of the ocular microbiome? Are any kind of eye products that people use like drops, can they interfere? What do we know about that?

Dr. Fishman: Right. Those are great. Certainly areas that people are looking at. In the eye, there are so many aspects of the eye in terms of the ocular microbiome of the eye that makes it complex because the thing about the microbiome of the eye is that it’s not only that we think a core microbiome exist in a very low level, there's a lot of other bacteria and other species of organisms that sort of “contaminate” those measurements and also the surface.

One of the interesting things, there's a lot of sort of noise, in the sense that there's the noise from contaminants at any one time on the eye can overwhelm the signal of the actual microbiome. But what does seem to occur is that it's very possible that when people have sort of acute issues is because they do get some sort of dysregulation of their normal biome by this sort of contaminant. The sort of things that can really change the ocular surface biome is exactly the source that you're mentioning. If you use makeup, if you use products—Latisse, for instance, the Latisse, which people use to make their eyelashes grow longer contain a lot of— basically cause of the eyelashes that have more inflammation, more debris on them and that those are basically culture plates for bacteria on the eyelashes. That really does change it.

A lot of what you're mentioning really is sort of the dry eye disease realm, which is that all these different products that people use, including unnecessary eye drops or things like viral bacterial conjunctivitis, which you wouldn't use an antibiotic but that changes the microbiome. The other thing that is very fascinating is parasites. It turns out Demodex, I'm sure you—maybe we had many shows on Demodex, but Demodex is a big, big deal, and there is an interesting sort of life cycle of Demodex in the lashes and how that relates not only to the skin microbiome, but actually of people who have dysbiosis of their intestine. It’s just incredibly fascinating and it plays into the whole ocular rosacea story as well.

Chris Kresser: Not too long ago we had a periodontist, Al Danenberg, who's been through my clinician training program and is a really knowledgeable guy. He has looked at the connection between the gut microbiome and the oral microbiome and has found from his perspective and from what the research is showing that when there's a disruption in the oral microbiome, it's usually or often driven by dysfunction of the gut microbiome rather than the other way around, although certainly we know that infections in the mouth can influence the gut and other parts of the body, but because stomach acid protects against, hopefully if it's sufficient, a lot of what we would swallow and the saliva from the mouth that the relationship is probably more strongly influenced in the other direction. Has there been much work done on the influence of the gut microbiome on the ocular microbiome?

Dr. Fishman: That's a huge area that people … there's a lot of really interesting work, but just to kind of go back to what you said, there was a really interesting paper that came out that talked about the oral microbiome linked to neurodegeneration and glaucoma.

Chris Kresser:  Ah …

Dr. Fishman: We actually know that there are people with worse oral disease and dental disease. Actually, you have higher rates of primary glaucoma than other people, and that was a very well done study that was recently published. Essentially one of the things that we've known forever, and as a medical student, we learned very early in the game, the connection between ulcerative colitis, Crohn's disease, and uveitis. You may have touched upon before, but that is one of the most clear-cut associations that we have enough knowledge. In fact, ophthalmologists often sometimes will look … brilliant clinicians … when the person comes in and we see uveitis and then we do a little bit of the history and it turns out that they have Crohn’s and then we send them to the GI specialist and the GI guy thinks we're brilliant. We've discovered Crohn’s disease by looking in their eye and yet there are a few associations.

What's interesting is that there are multisystem disorders, autoimmune diseases that are associated with uveitis that are absolutely related to the gut and in other areas. That's an area that NIH is doing a very—there is a big push to look at the association. In particular, some of the work they're doing with T cell activation, both protective T cells and non-protective T cells, and how it influences uveitis, and they've been looking at some really interesting experimental autoimmune uveitis models, the EUA, so to speak, and they looked at how the regulatory T cells in the gut and other tissues really affect the uveitis and so forth.

Chris Kresser: I think there are probably a fair number of listeners who are not that familiar with disease. Uveitis being an inflammation of the middle layer of the eye, right?

Dr. Fishman: That's right.

Chris Kresser: With the connection between the gut and depression for example, the speculation is that in terms of the mechanism is that inflammatory cytokines are produced in the gut and they enter the bloodstream, perhaps because the barrier is permeable and they travel through the blood and they cross the blood–brain barrier and they suppress the activity of the frontal cortex, and that's one way gut pathology can lead to anxiety and depression.

In the case of the connection between the gut and eye disease, let's take ulcerative colitis and Crohn's, which are both autoimmune GI pathologies. Is the speculation that the systemic inflammation caused by the autoimmune disease is what's causing the inflammation in the eye, or is it that something related to a disruption of the microbiome leading to maybe the production of certain chemicals or inflammatory cytokines or something that's more specific to the microbial ecology of the gut is the contributing factor, or do we just not really know?

T cell activation in the eye

Dr. Fishman: One of the thoughts, and there was a paper that … and these are all interesting, really recent papers like 2015 to 2016, but there’s that commensal microbiota and bacteria in the gut that activate T cells. These T cells then circulate and then actually pass into and through the retina, in other parts of the eye, to then activate directly. It’s definitely via the immune system, but there are very specific immune cells that actually can penetrate into the eye. There's always been that thought that the eye is immunologically pristine, and that really is obviously not the case, but there are very selective T cells that can in fact get into the eye or pass into the eye, and so that's what we think that is going on, is that there's a dysregulation in the microbiome of the gut.

As you pointed out, you get T cell activation, and then it actually activates the local immune system in the eye. Actually, a really interesting situation that we see with respect to that, we actually can see diseases like sympathetic ophthalmia, which is a disease where if you injure one eye, activation of the T cells from one eye actually can go to the other eye, and you can actually lose the other eye, so you could actually have a question where are you …

Chris Kresser: Oh, wow.

Dr. Fishman: Yes, it's awful. That's why people have to get their eyes enucleated or taken out when they have a trauma. They have to do that within about 10 to 15 days or sooner because they can get this autoimmune activation that can actually blind them in the other eye. It’s just fascinating how that works, but that is sort of the same idea in the gut that you get with activation, and it causes inflammation. One of the things that we know, Chris, and this is my own personal experience in my practice, and I've seen this over and over and over again, is that my uveitis patients, they always come in with an active disease, almost always some kind of a gut-related situation that sets off their uveitis or inflammation. They'll come in and I’ll say, “What did you do last week?” “I was in Las Vegas and then we ate a lot of carbohydrates,” and these are patients who are very strict about being on a gluten-free diet, and they just say they cheated, so to speak, they had a bad weekend, fun weekend, but now they're paying the price and then they come back and they get uveitis. I can't tell you the number of times I've seen that. It's just clear cut. That's actually withm in particular, HLA-B27 uveitis. I don’t know if you have covered that, but that’s a big area.

HLA-B27 and genes that play an important role in immune function

Chris Kresser: I love to hear a little bit. I’m familiar with HLA-B27 and AS, ankylosing spondylitis, and the connection there. In fact, in our clinic, we will often test patients for HLA-B27 if they have joint pain, and if they test positive for Klebsiella bacteria on the stool test, I forget the name of a physician in London who discovered that connection, but then we’ll often put them on a low-starch diet and will treat the Klebsiella, and their joint pain will go away, or at least that will significantly improve. Tell me more about HLA-B27 and the eye.

Dr. Fishman: That’s our biggest immune screening. We screen for that in every single uveitis patient and screen for HLA-B27. In fact, 50 percent of every non-necrotising anterior uveitis, which is just a fancy word for basically idiopathic, meaning we don't know what the cause is, it's almost always related to an HLA-B27-positive uveitis, and so we see that all the time. Those patients are particularly sensitive to changes in their diet, and a lot of those patients, I will really push for strong control, at least in my practice. We always start off with a gluten-type restriction because that seems to be one of the big areas that sets off uveitis. HLA-B27 is such a prominent factor in most of our inflammation. You can also get sclerites with HLA-B27, you can get uveitis, you can get episcleritis, any of the autoimmune diseases around the eye seemed to be linked to that marker.

Chris Kresser: Just for the listeners, if your eyes are glazing over here, we're geeking out a little bit, but I want to back up. HLA-B27 is a gene, and it's one that plays a really important role in immune function. Its prevalence varies around the world in different ethnic groups and populations. I think it's about 8 percent in Caucasians, maybe this 2 to 9 percent in Chinese, 4 percent North Africans. As I was mentioning before, the association that I was most familiar with, I'm really fascinated to learn about the connection with uveitis is with ankylosing spondylitis. Back in the ’80s, there was a physician in London, whose name I'm unfortunately forgetting at the moment, and he was treating patients with AS, and by accident some of them he put on a low-carb diet for weight loss, and their AS improved dramatically. He did some more research and he found that there is a greater abundance of Klebsiella in stool samples of patients with AS, and then he found that Klebsiella bacteria that have preference for starch, and the patients that he put on a low-carb diet were of course eating a lot less starch. The low starch intake starved the Klebsiella and reduced the Klebsiella, which then reduced the autoimmune attack against the HLA-B27-expressed enzymes that were in the joints, and that's reduced the symptoms of AS, or ankylosing spondylitis, but there was later research that showed that sometimes can be connected to Crohn's disease. You just told me that Crohn's is connected to uveitis. Things like this, there’s a very interesting connection going on here, and that it may possibly a low-carb, low-starch diet, if it works for AS and HLA-B27, might be effective for uveitis.

Dr. Fishman: Absolutely. I basically, in a very non-scientific way, have my patients try these diets and often they don't want to go on to these heavy-duty immunosuppressants like methotrexate or Imuran. They want a natural … not natural, but they want a way to control the inflammation not to do these other sources. They will grab it, and a lot of the way I practice is I've learned so much from the multitude of patients who tell me, maybe the patients who have seen you as well, I learn from them what works, and I can then pass it on to other people. But in terms of the gut association with HLA-B27, it’s fascinating when you were mentioning Klebsiella, it turns out that Klebsiella as well as other bacteria … and in particular, there's a big connection with blepharitis and dry eye disease. In fact they did a study where they looked at patients—Bacillus was the other one—they looked at a setting where they looked at patients who had dry eye disease, and it turned out that Bacillus and Klebsiella were the huge association with blepharitis and dry eye disease. Just as an aside, another very interesting thing, because I'm very interested in dry eye disease and a lot of people with ocular rosacea, there is that story that the microbiome of your gut are being eaten, so bacteria that actually get eaten by the parasites, which hurt the Demodex on your eyelashes and your hair follicles, they eat the bacteria, then the parasites puke up the bacteria, and then the products and the exogenous components from the bacteria then irritates the eyelashes and the meibomian glands, which are glands in your eyelid, cause severe dry eyes. That's this interesting lifecycle between bacteria, Demodex.  The other thing that I've looked at, and I know that you guys have talked about SIBO, and there seems to be this association with SIBO, bacteria, blepharitis, Demodex and ocular rosacea and dry eye disease.

Nutrient-dense and anti-inflammatory diet for eye health

Chris Kresser: Fascinating. I mean, there's so many directions, but it all really comes back to, I mean, I think one of the things I like to emphasize, these discussions are fascinating and they're important, and these lines of research are really crucial to figuring out what's going on, and at the same time it comes back to the same basic steps that we need to take. Eat a nutrient-dense, anti-inflammatory diet, make sure you're taking care of your gut microbiome, avoid unnecessary antibiotics.Make sure to eat plenty of fermented foods and fermentable fibers. It can be easy to get overwhelmed by the complexity of all of these connections, but the good news is that usually it's just the same simple steps that we need to take in order to protect our health.

Dr. Fishman: Absolutely. One of the things that we found, and you'll just be amazed, ophthalmologists, we have been running the largest nutritional study in the history of mankind, and it was for macular degeneration. That statement is not a trivial one. I don't know if you’ve talked about this, and essentially the use of lutein as the advancement in your diet. There are a lot of interesting connections between the intestine and macular degeneration, and there's a big suggestion that the intestinal dysbiosis as seen in AMD patients … and when you're doing these supplementations, you're really supplementing the intestinal microbiome to reduce inflammation in the retina, which is actually the cause of macular degeneration, so it's just incredibly fascinating. Every time I leave my patient, I feel that there are two things I want you guys to leave this office with because I don't have the bandwidth, obviously, that your practice has in terms of … I have this focus on different things, but I tell them spinach pills, which is just spinach and omega-3 fatty acids. Omega-3 fatty acid is a very interesting controller of eyelid health and dry eye disease despite the fact that there was a recent paper that came out that disputed that, and I would really argue that that was not a very well-done … it was a study that was well done, but they had a lot of problems with it. My two big go-to things at least in my practice are spinach and fish.

Chris Kresser: That certainly fits into the context of the nutrient-dense, anti-inflammatory diet. It's really fascinating to me how the change, I think, that's happening in medicine, not just in functional integrative medicine but even in conventional medicine, that we started out allopathic medicine grew out of this Cartesian dualistic framework, where the body is basically just a bunch of disconnected parts that are kind of loosely connected, but not really influencing each other, and now we're really starting to understand that under traditional systems of medicine, they certainly didn't get everything right, but the one thing that they did get right was this idea of holism, that every part of the body is connected to and influences the body as a whole.

Now we're seeing this, I think, really play out. Look, it's Crohn's disease and ulcerative colitis increase your risk of eye inflammation. We now have the inflammatory cytokine model of depression that shows that inflammation in the gut can cause inflammation in the brain and symptoms that mimic depression. We've got connections between dysfunction in the HPA axis and stress and all kinds of skin conditions like eczema and psoriasis. I mean, the list goes on and on, and now we're adding to this the connection between the oral microbiome and the gut microbiome and inflammation in the eye, which even just, I think, 20 or 30 years ago would have been completely dismissed as a woo-woo kind of out-there stuff. It's just encouraging to me that we're really starting to move, no matter what kind of perspective on medicine, we're talking about into a more holistic view of the body.

Dr. Fishman: There was an interesting paper where one researcher looked at treating, it wasn't a corneal ulcer, but they were treating sort of a conjunctivitis using a probiotic eye drop.

Chris Kresser: I was going to ask you about that.

Dr. Fishman: There’s a disease called vernal keratoconjunctivitis, and that’s a pretty tough one to treat. Vernal means spring, and basically it’s allergic conjunctivitis. A lot of kids get it, and the way we typically treat that is with steroids and so forth, which you obviously don't want to do for children. There was a paper back in 2008 where they looked at using a probiotic eye drop, and they found it was equivalent to some of the other drops that they were using, which to me makes complete sense. I had a very interesting case recently of a patient who had actually an open globe. She actually had some sort of a tube that was put in for glaucoma, and it eroded through the conjunctiva. Bottom line, you see an open globe and she had opened up for essentially six months and nothing happened. She didn't get an infection, nothing. For whatever reason, she had a very well-controlled ocular biome.

One of the interesting questions that we're now looking at is how do the intestinal, oral, or skin biomes relate to the ocular microbiome? I think it's a pretty clear situation, and we know and I've had private conversations with some pretty famous microbiologists, anything that comes out of your intestine is going to be in your eyes, so basically just think of it that way. I mean, it doesn't sound great, and I joke with my patients, “You're basically getting poop in your eyes, and it happens all the time, every single day.” That’s what happens, not to be completely crap, but that is the connection.

Chris Kresser: Yes, yes. That's interesting. The probiotic eye drop reminds me of, I talked about this before, the nasal microbiome and the connection between the nasal microbiome and sinusitis. Dr. Susan Lynch at UCSF has done some really interesting work in this area. She did a fascinating study that was both animal and human, and they had an animal model of sinusitis, and they found that the main difference between animals with sinusitis and the controls was not—and this was true in humans too—was not the presence of certain pathogens. It wasn't that the people with sinusitis had much higher levels of fungus or certain species of pathogenic bacteria. The biggest difference between the two groups was microbial diversity.

Dr. Fishman: Right.

Chris Kresser: The people who were the controls, the people who didn't have sinusitis, had a much richer diversity of healthy protective bacteria, whereas the people who had sinusitis had a lower diversity, even when the presence of pathogenic species was basically the same. There was no difference between the two groups. The difference was that the healthy people had much higher levels of protective bacteria, and then she went a step further, and in the animals, they treated them with antibiotics until they were basically depleted of the microbiome in both the healthy controls and the animals with sinusitis. And in one group of animals, they didn't do anything. They just let the bacteria grow back as they would, and then the other group, they inoculated them with a protective species, Lactobacillus sakei, which they had observed in higher numbers in the healthy controls. And those animals that were inoculated with that nasal probiotic didn't develop sinusitis or anything the other animals that were not inoculated with that. That really actually speaks to probiotics in both maintaining and then restoring a healthy microbiome as being a more effective strategy than using antibiotics or antimicrobials to try to get rid of pathogens.

Dr. Fishman: Right. When you mention those two things, there were two interesting things that come to mind. The first one, just to let you know that there was a paper that came out in Nature in 2016 which said exactly the same thing. They were looking at Sjӧgren's disease—for your listeners, it’s one of the most severe forms of dry eye disease and other dry parts of your body. They found the exact same finding, that people with the severity of Sjӧgren's disease was inversely correlated with microbial diversity in your gut.

Chris Kresser: Wow.

Dr. Fishman: And with just as clear as day. It was just super clear that this was the case. We know, and I know from my own clinical experiences, that people who have, do have, a much higher control level, people who do a better job in terms of their diet, people who are more precise about the food that they eat and so forth, do much better with dry eyes. Dry eye disease, for the longest time, we've been treating dry eye disease with omega-3s or any type of fatty acid, but any sort of derived can lead to that. What I always mention is that, is it actually the omega-3 acting directly in your eye, or is it basically an activation, a biological cascade, that then causes the improved function in the eye? I clearly believe that it is a cascade effect because there is no way that just a simple little fish oil capsule could have that much of an improvement in people with dry eye disease.

Chris Kresser: Right, right.

[Crosstalk]

Chris Kresser: Go ahead, please.

Antibiotics prior to surgery

Dr. Fishman: Yes. I just have one other really interesting comment, which was one of the things that is interesting is that you talked about treating infections with basically displacing the bad bacteria with “good bacteria” and so forth, and that whole concept, which makes a lot of sense. One of the things that we've seen is that in eye disease, especially in ocular surgery, we routinely treat our patients basically from medicolegal reasons with antibiotics prior to surgery.

Chris Kresser: Right.

Dr. Fishman: It turns out that the studies are coming out that there's no data whatsoever to support those claims.

Chris Kresser: Yes.

Dr. Fishman: Those are billions of dollars a year in an antibiotics that were sold by pharmaceutical companies to basically do nothing and maybe, who knows, but maybe actually not even improve outcomes, but maybe make outcomes worse by selecting for bacteria that if it does get into eye, it actually would be a much worse situation.

Chris Kresser: Right.

Dr. Fishman: That's really interesting data that we have.

Chris Kresser: That happens, of course, not just in the world of the eye, ocular issues, but of course in the dental surgery, where patients will often come and say, “Oh, I'm about to get this dental surgery. My dentist is just prescribing antibiotics prophylactically.” Of course I've had the thought, “Well, okay, does this become a self-fulfilling prophecy?” Because we know that disruption of the oral microbiome with antibiotics can actually predispose you to an oral infection, and so by prophylactically prescribing an antibiotic is not really prophylaxis, or is that actually more likely to develop an infection? And as you said, not only have you reduced your body's ability to fight the infection, if it does happen, by reducing the number of beneficial protective bacteria, you've also potentially contributed to creating a more resistant strain of pathogenic bacteria by killing the ones that were least … the types of pathogenic bacteria that were least robust and just leaving the ones that were more robust.

Dr. Fishman: Well, there is some evidence that suggests that may actually be the case. I mean, with eye surgery, we use povidone iodine before surgery. That is the gold standard and at least cuts down sort of universally all … it doesn't select, do you know what I mean? You're not selecting for bacteria. You're basically wiping it out. Antibiotics, on the other hand, are probably selecting for it. That’s a good example where that period self-selecting bad bacteria really might be coming true. It’s very interesting where we’re going, especially with the eye, because there are still many “idiopathic” diseases and infections that really relate to the biome, not only of the eye, but also the gut being the cause of it.

Chris Kresser: Who knows? Maybe someday you'll go to the dentist and you'll get a dental probiotic instead of antibiotic for an infection. Maybe you’ll go to your ENT for an ear infection, and instead of putting antibiotic ear drops, they’ll put in probiotic ear drops. You’ll go the ophthalmologist and instead of getting antimicrobial treatment, you'll get probiotic eye drops. Seems that's not far-fetched at this point.

Dr. Fishman: Not at all. In fact, you might argue we’re already doing that through indirectly by using our gut as a way to … [crosstalk]

Chris Kresser: Right. To modulate.

Dr. Fishman: Correct.

Chris Kresser: Well, this has been really fascinating, Dr. Fishman. I've enjoyed talking with you, and I think the listeners are really going to get a lot out of this, and it's hopeful. I feel hopeful to know that there are folks like you who are exploring these new frontiers and really kind of pushing the boundaries and questioning some of the most basic assumptions that we've made and finding a new path forward that could lead to better, safer treatments. Where can folks learn more about your work or if people are in the Bay Area? It sounds like you definitely are still seeing some patients. Tell us where people can learn more.

Dr. Fishman: Sure. Well, they can always find me on my website, which is www.fishmanvision.com, and they can get involved in my practice in multiple ways. I definitely see patients. Half the time I'm seeing patients, half the time I'm doing research.

[Crosstalk]

Chris Kresser: It looks like they can do some video consultation as well. Is that right?

Dr. Fishman: Yes. For people in California, I can do video consultations if they can't make it to the office. Especially for dry eye disease, it’s very helpful.

Chris Kresser: Right, right. Great. Well, keep us posted on your research. We’d love to hear it, stay in touch, and have you back on the show at some point and just keep track of your work. These are really exciting developments.

Dr. Fishman: I really appreciate the opportunity, and I wanted to thank you because we've shared some patients, and their lives have actually changed because of the work that you're doing with them, so thank you.

Chris Kresser: Fantastic. It’s my pleasure. Take care.

Dr. Fishman: Okay, thank you.

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