.png){kind=small}
.png){kind=small}
BackTable / ENT / Article
Allergy Medicine & The Sinus Microbiome
Iman Iqbal • Updated Jul 31, 2025 • 32 hits
Allergy medicine is evolving rapidly as researchers uncover new connections between the sinus microbiome and immune health. The communities of microbes living in the sinuses and nasal passages play an important role in how the body responds to allergens and inflammation. While the gut microbiome has long been a focus of study, the impact of treatments like immunotherapy on the sinus microbiome is an exciting new frontier with many unanswered questions.
Understanding how various treatments such as antibiotics, steroids, and biologics affect these microbial ecosystems could lead to more effective and personalized allergy care. This article explores the complex interactions between the microbiome and immune system, with otolaryngologist, Dr. Jennifer Villwock highlighting how shifts in microbial diversity and immune signaling may influence treatment outcomes and long-term health.
This article features excerpts from the BackTable ENT Podcast. We’ve provided the highlight reel in this article, and you can listen to the full podcast below.
The BackTable ENT Brief
• The sinus microbiome is an emerging area of research with implications for allergies, chronic sinusitis, and immune function, showing interconnectedness with gut and other body site microbiomes.
• Dysbiosis, or microbial imbalance, contributes to inflammatory and allergic diseases and is linked to systemic conditions like MS, Parkinson’s, and autoimmune disorders.
• There’s no universal "healthy" sinus microbiome. Even potentially pathogenic bacteria like S. aureus can be present in asymptomatic individuals, complicating diagnosis.
• Immunotherapy (especially sublingual) modifies both immune pathways and microbial communities, lowering IL-4, IL-5, IL-13, and increasing IL-10, which supports tolerance.
• Biologics can effectively suppress specific cytokines but may oversimplify immune modulation and risk unintended microbiome shifts.
• Microbiome recovery is slow after interventions like surgery or immunotherapy, taking more than a year in some cases, highlighting the need for long-term management.
• Adjunctive treatments like topical probiotics or combining sublingual immunotherapy with procedures (ex: septoplasty) may support better microbiome outcomes and symptom control.
• Sublingual and subcutaneous immunotherapies are similarly effective immunotherapies with some differences in delivery method, cost, and adherence.
Table of Contents
(1) An Introduction to the Sinus Microbiome
(2) Bacteria Diversity & The Immune Response
(3) How Allergy Immunotherapy Affects Sinus Microbiome Health
(4) Sublingual vs Subcutaneous Immunotherapy
An Introduction to the Sinus Microbiome
The human microbiome exists throughout the body, on the skin, in the gut, sinuses, and even areas like the middle ear. It represents a complex ecosystem of bacteria, viruses, fungi, and other non-human cells that live in and on us. While the gut microbiome is the most widely recognized, likely due to its popularity in supplement marketing, growing research is shedding light on the significance of the sinus and nasal microbiomes, particularly in relation to conditions like chronic sinusitis and allergies. Treatments such as antibiotics, steroids, and immunotherapy can all impact these microbial communities, sometimes in ways that are still not fully understood. For instance, although sublingual immunotherapy is designed to act locally on mucosal surfaces, studies show that it can induce changes not only in the gut microbiome but also in the nasal microbiome, suggesting a systemic or interconnected effect across bodily microbiomes.
Microbiomes play a crucial role in maintaining health by regulating immune responses, beginning as early as fetal development. In a healthy state, the microbiome helps the body recognize what is safe and prevents inappropriate immune reactions. However, when the balance of microorganisms is disrupted, a state known as dysbiosis, it can contribute to a wide range of inflammatory and allergic conditions. Researchers analyze microbial diversity, proportions, and metabolites to understand these imbalances and their implications. Dysbiosis has been linked not only to allergic and atopic diseases but also to gastrointestinal issues and systemic inflammatory conditions like autoimmune diseases, multiple sclerosis, Parkinson’s, and Alzheimer’s.
[Dr. Ashley Agan]
That's cool. Very interesting. Great. Then today we're talking about the microbiome as it relates to allergy. I guess maybe we can just start with talking about just basics in setting the stage. When you're thinking about allergy as it relates to the microbiome, in pre-reading for this, I saw articles that talked about both how sublingual immunotherapy can affect the gut microbiome as well as looking at the nasal and sinus microbiome and so tell me more.
[Dr. Jennifer Villwock]
Yes. You're like, so what's up with all that?
[Dr. Gopi Shah]
Which bugs are we worried about?
[Dr. Ashley Agan]
Before you even do that, can you just explain in general what is a microbiome? Where do we have them? Just give us the basics first.
[Dr. Jennifer Villwock]
Yes. We have a microbiome everywhere. Anywhere that basically our body is interacting with the outside world and even internally, there's an active microbiome there. I think for most people, the most common one that we hear about so much, and I think part of that is due to marketing of different supplements and other things, is the gut microbiome. I think a lot of our patients, especially our sinusitis patients are very well aware of the importance of the gut microbiome because they're treated with antibiotics, sometimes very routinely, and they experience all of those GI type symptoms, which sometimes can be worse or become chronic and overshadow some of the original reasons that they came to see us.
There's a skin microbiome. We're going to talk a little bit about the sinus microbiome. I think we're really in a time in science, at least, where there's a lot of interest in figuring out, well, how do all of these things really relate? To your point, well, how is it that sublingual immunotherapy, the benefit of it is supposed to be, it stays on the mucosal surface, low risk for side effects, et cetera, but somehow it's changing the gut microbiome. What's happening? Also, I think that we're going to be learning a lot more in the coming years about, well, what are the side effects and how long are there changes to the microbiome with the different treatments that we offer, whether it's antibiotics versus immunotherapy versus steroids, et cetera.
I think for a lot of patients, especially, I always picture my recalcitrant patients who are like, "I've done everything I think I'm supposed to do" and they're not getting better. I'm really hopeful that as the evidence emerges, we'll have more explanations and hopefully understanding those mechanisms will lead to better treatments.
[Dr. Gopi Shah]
I always think about bacteria when I think about the microbiome, but technically it's also parasites and viruses and non-human cells. We have way more non-human cells living in us and on us than we do human cells.
[Dr. Jennifer Villwock]
Yes, absolutely. I think for most of the scientific disciplines, it's the study of the bacterial microbiome that has the most literature, but you're exactly right, there's bacteria as well as viruses, as well as fungi, bacteriophages. There's all sorts of things that are happening in that complex interplay that we can neither see and oftentimes we don't have the optimized ways to even test for all of those things.
[Dr. Ashley Agan]
Are these protective or do they ever not help us?
[Dr. Jennifer Villwock]
Yes, so for the most part, you can think about, I guess, two different states. One is the healthy state where we know that our microbiome, it is in fact protecting us. There's a lot that begins even at the fetal level in terms of recognizing what is self, what is safe, et cetera. There can be things that happen very early in development that are linked to the atopic disease and other diseases going forward because of the dysregulated immune system, not recognizing things as it's supposed to, et cetera. On the normal side of things, everything is running in sync.
All these invisible players that we can't see, it's all working. We're staying nice and healthy. Then you get to the dysbiosis side, meaning something just isn't right here. There's a variety of ways to assess or test for that. You can look at the overall number of different species. You can look at the overall proportions. We can compare those versus disease states and look at also things like metabolites of that whole bacterial microbiome. How is that causing differences in the products, et cetera that are excreted? Dysbiosis is associated with a lot of different things.
It certainly can be associated with different atopic or allergic diseases, which is where a lot of my interest is. There's also a lot of implications for things like irritable bowel disease. There's a whole emerging body of literature about how when your microbiome isn't optimized and you're in that dysbiosis state, there's more inflammatory products that are made. Then how does that play into other things that we know are related to inflammation like autoimmune diseases, multiple sclerosis, Parkinson's disease, Alzheimer's? There's all sorts of research in all of those other fields as well.
[Dr. Ashley Agan]
The microbiome in the gut is different than in the sinuses or are they similar? Then do we have a microbiome in the middle ear? I just think of mucosal linings that are all connected.
[Dr. Jennifer Villwock]
Yes. There's a microbiome everywhere. To your question, there have been some studies looking at, for example, sublingual immunotherapy that has been administered and it has changed the microbiome in the gut, which I think you alluded to in the beginning. Follow-up studies have showed, oh, actually the proportion of bacteria in the nose mirrored the change that happened in the gut, which again seems like, well, how is this happening? I don't think anybody has the answer to that, but it does show how all of these microbiomes and all of these hidden pieces are really connected in terms of human health.
Listen to the Full Podcast
Stay Up To Date
Follow:
Subscribe:
Sign Up:
Bacteria Diversity & The Immune Response
While diversity of bacterial species is generally considered beneficial, there is no universally defined "optimal" composition. As Dr. Villwock describes, studies of patients with chronic rhinosinusitis show variable findings, some demonstrating decreased microbial diversity compared to healthy controls, while others show minimal or no differences. A key complexity arises from the fact that individuals can harbor bacteria typically labeled as pathogenic, like Staphylococcus aureus, yet remain completely asymptomatic. This makes it difficult to categorize people cleanly as either "healthy" or "diseased" based on microbiome profiles alone. Given the wide variability in bacterial makeup influenced by geography, demographics, and symptom states, establishing a universal “recipe” for a healthy sinus microbiome is likely unrealistic.
Instead of focusing solely on bacterial composition, researchers and clinicians are increasingly examining the immune response associated with microbiome changes. For instance, shifts in bacterial populations can influence downstream cytokine production. In allergy treatment, interventions like immunotherapy not only retrain the immune system but also result in decreased levels of pro-inflammatory cytokines (such as IL-4, IL-5, and IL-13) and increased levels of anti-inflammatory markers like IL-10. Similar patterns are observed when the microbiome shifts toward a more diverse and presumably healthier state. Thus, even in the absence of a clearly defined microbiome composition, improvements in inflammation markers can serve as indicators of treatment success. The key takeaway is that greater microbial diversity is generally favorable, but strict bacterial ratios are not necessary or universally applicable.
[Dr. Ashley Agan]
When you're studying microbiome changes, tell me, is there an optimum diversity constellation of bacteria or we're just looking at, oh, they seem to have more of this before when they had worse symptoms and then we did this treatment and now they have less of this one bacteria after we did. Is there a standard? Like we know that you should have this, if you had a recipe, we want this much staph and this much strep and blah, blah, blah. I think that's the hard part when I'm listening to other podcasts with people talking about it.
It seems like that we don't quite know what are we striving towards? It's just, we're just noticing, oh, some people who have more of this seem to have this problem. We're noticing some patterns, but I feel like that makes it hard to study it, maybe.
[Dr. Jennifer Villwock]
Yes, it does. I think it gets really complicated in the sinuses as well, because we know that there are some folks that are colonized with bacteria that we typically perceive to be pathologic, but they're not causing them any symptoms. Then how do you separate out, well, are those really healthy control people or are they in their separate little category? Then to your point, to do a study, like how many of these little categories are we going to have? Because we know that there's so much variability and there's been a number of recent, like in the past 5 to 10 years, different systematic and narrative reviews that try to summarize we're generating all of this information. What does it really mean?
For most studies, when you're looking at populations of people that have chronic sinusitis, you see a decrease to no change when comparing to control subjects and things like the diversity and the richness. You sometimes see differences between your disease state and your control group, but not always. Yes, it gets very challenging to know, to your point, well, what is truly the best mix? I think that what we'll see is that's highly location, demographic, disease state, symptom state dependent in a way that we're not going to have a great recipe for everybody.
I think that's also, sometimes when things get complicated in my mind, I'm like, let's just not focus on the complicated part. Let's find another little tidbit that we can focus on and that's a little bit easier. That's why I'm a person that tends to go down rabbit holes if you guys have not already learned that about me. One of the things that I think is really cool is that yes, there's all this microbiome, different bacteria, proportions of different stuff in the sinuses. We also know downstream there's things that are going to happen or be produced that are either going to be pro-inflammatory or not pro-inflammatory.
I think about that a lot in the context of the allergy patients that I treat because we know that as we do things like immunotherapy and we're actually retraining the immune system, we're expecting decreases in certain cytokines and cell populations, et cetera, that are going to correlate with decreases in symptoms. The decreases are the things that all the new biologic medicines are focusing on. Like we're shunted towards the allergy side of things. We know we're going to have more things like IL-5 and IL-4 and IL-13. There's biologics for all of those things now.
The other thing that we know is going to happen as we make allergies in the atopic pathway better is we're going to have increases of anti-inflammatory cytokines. Those are things like IL-10. Going back to the microbiome, we know that sometimes when there are these shifts in the microbiome, it also leads to increases in anti-inflammatory cytokines like IL-10. Now, rather than getting lost in all of the weeds of like, oh, well, what's the proportion and how do we manipulate it, et cetera, sometimes in very specific contexts like allergy, you can think about, well, if I'm treating people, regardless of what their microbiome is, it should shift towards a less inflammatory state and I should be seeing some of these anti-inflammatory cytokines as a result.
How Allergy Immunotherapy Affects Sinus Microbiome Health
Biologics target specific immune pathways, such as IL-4, IL-5, or IL-13, to reduce inflammation, but they may shift the immune response too far in one direction, potentially affecting microbial balance. Immunotherapy, in contrast, encourages immune tolerance through gradual exposure to allergens and is considered a more physiologic and balanced approach. It mimics the natural process of immune development, as seen in early childhood exposures, and is less likely to disrupt the microbiome.
Predicting individual response to immunotherapy remains challenging, especially in patients previously treated with antibiotics, steroids, or sinus surgery, which may alter their baseline immune and microbial state. IL-10 is being explored as a potential early marker to identify responders. However, the timeline for microbiome stabilization after interventions and the definition of a “healthy” microbiome are still unclear. Not all patients with positive allergy tests experience clinical symptoms, highlighting the need for careful treatment selection.
[Dr. Ashley Agan]
You just talked to us a little bit about the biologics and how that might shift certain anti-inflammatory cytokines in the microbiome. Are we ever doing too much one way, whether it's immunotherapy, biologics, that we just said diversity and the different types of cells in the microbiome is protective. When we do treatments, are we ever doing too much to cause it to shift towards just IL-10, which may or may not be the only thing we want in the microbiome and in our sinuses?
[Dr. Jennifer Villwock]
Yes, that's a great question. I actually I'm not aware of any literature showing or any studies that have been done actually on a lot of these newer biologic medications and how they might impact the microbiome. That's a great question, because we know we're fundamentally altering the different immunologic pathways. I feel I guess, if we're talking about, well, how do we feel about immune system manipulation when it's in the context of pharmacologic things versus immunotherapy? I would say that my hesitations in terms of any sort of long-term side effects are much less on the immunotherapy side of things just because it's been documented to be so safe for so long.
We know that we're manipulating, yes, the differentiation of different cells. We want higher populations of their T regulatory cells, et cetera. It's in a much more, at least in my opinion, physiologic context, than just saying we're going to introduce something that's going to block these particular cytokines and artificially shunt things one way or the other. My hypothesis would be that there's less of a risk for pushing people towards that dysbiosis using things like immunotherapy.
[Dr. Ashley Agan]
Yes, I think of that, too, because in my mind, when I think about, for example, like sublingual immunotherapy, I think about little kids who are always putting things in their mouth and sampling their environment. That's them, like when you think about hygiene hypothesis and if you grew up in a less hygienic environment, then you did your own sublingual immunotherapy by sampling the environment, being exposed to stuff. Maybe if you didn't have that exposure, you now we're doing that in a different way later in life, being like, here, let's have a little dust, have a little grass.
Yes, it feels more like you're just tapping into the body's natural way of going down that pathway of tolerance. Is there a certain state that you want your microbiome to be in to be more or less responsive to immunotherapy? If you have a patient that, for example, history of allergies, history of chronic syntheses, maybe they've been on lots of antibiotics at this point because they've been treated for lots of six weeks of whatever antibiotic, twice a year. We've done oral steroids, we've done, rinses with steroids and allergy medications. We've done all that.
Now we are thinking, immunotherapy. Does a patient like that who's had lots of different types of medications, potentially surgery, how that might affect the microbiome versus somebody that really is naïve to a lot of that, starting immunotherapy, do you think of them differently and sort of how that microbiome might play a role in how responsive they are?
[Dr. Jennifer Villwock]
That's a great question. I think the honest answer is that we don't have great predictive mechanisms right now to know who's going to be a good responder and who isn't. There are some folks who have done research investigating, we're going to start someone on immunotherapy. We know that IL-10 in particular is something that we can analyze from the saliva as well as the serum. We should be seeing a pretty quick uptick of that particular cytokine. Maybe, if you're able to assess that early on in the immunotherapy course, taking a step back, recognizing that most of the time we're going to recommend that people be on immunotherapy, whether it's subcutaneous or sublingual for a treatment course of three to five years.
It's automatically a long buy-in. I talk to patients about that all the time, and one of the things I counsel them on is, well, we're trying to retrain your immune system. It's just like training a small human, or a small pet. You can't just train them consistently for like three to six months and then be like, "Oh, they're going to behave for the rest of their life." We know that you have to continue to train these little creatures for years if you want that consistent behavior that you're looking for and the immune system is the same. To your fundamental question, well, wouldn't it be nice if we had an early way to say this person's probably going to be a great responder after six months to a year, versus just saying, well, I guess we'll see how you're doing as things go on and potentially and tweak your recipes or reassess.
IL-10 is a potential candidate for that. As you mentioned, there's a lot and our patients are complex. The patients that we see in clinic are not the ones that are presented to us in the textbooks or on the in-service exam, right? Where it's a very, here's the patient, it should be a relatively clear answer. Those are not the folks that are coming to us in clinic. There's so much that's going on there. there's been studies, Dr. Hauser et al. did some 8 to 10 years ago looking at the microbiome in the sinuses after surgery. Yes, and it does take several weeks to months to normalize.
Then the question is, well, did it normalize back to a pathologicy state or did it normalize all the way back to normal? How would we know that? I think there's still a lot of information to be found. I do think that immunotherapy in terms of allergy immunotherapy for appropriately selected patients is certainly an option, and certainly represents an avenue for potential improvement. The reason that I say inappropriately selected patients is that there's a difference between allergy sensitization that we can detect on testing and actual clinical allergy.
Really, your best allergy test is your HNP. It's talking with the person that's in front of you. Then we seek to quantify and correlate those symptoms with the things that are prevalent in our area that we know are most likely to be contributing to those allergy seasons. Then we have to do our double check and say, well, do the symptoms correlate with what's prevalent in our area? Are the symptoms happening at the time that we know that those antigens are most prevalent? If the symptoms are always in spring, but they're only sensitive to ragweed, you might say, oh, that doesn't quite make sense because weeds are a fall antigen. All their symptoms are in spring.
Even if the test says that they have sensitization, you're not going to treat them for an allergy that they don't have any symptoms during that time. There have been studies that have shown like, yes, allergy immunotherapy can help in addition to the traditional surgical options that we offer people. There was a recent study investigating the utility of adding sublingual immunotherapy to patients with nasal congestion, and they were all appropriately selected who were undergoing septoplasty and turbinate reduction.
They compared, well, what happens to the folks where we just optimize the architecture, we do our septoplasty turbinate reduction, and what happens to them where we do that, but we also do sublingual immunotherapy. The folks that were treated with sublingual immunotherapy had better outcomes in terms of reduction in nasal obstruction, et cetera, long-term. There's a lot to continue to think about.
Sublingual vs Subcutaneous Immunotherapy
While immunotherapy leads to changes in the nasal microbiome, the microbiome does not always return fully to a healthy baseline even after one year, likely due to the slow pace of immunologic changes. Studies suggest that a longer duration may be needed for full normalization. Supportive interventions like topical probiotics may help shift the microbiome toward a healthier balance during this process. Adding sublingual immunotherapy to surgeries like septoplasty and turbinate reduction has shown potential in improving long-term outcomes, including reduced nasal obstruction. This combination approach may offer better symptom control in select patients.
Sublingual and subcutaneous immunotherapy appear equally effective in modifying immune responses and improving symptoms. The primary difference lies in the route of administration and patient adherence. Subcutaneous therapy, typically covered by insurance, requires regular in-office visits. Sublingual options include FDA-approved tablets taken at home or off-label aqueous drops, which may not be covered and require out-of-pocket payment. Treatment choice depends on individual lifestyle, preferences, and insurance coverage, as adherence over the multi-year course is essential.
[Dr. Jennifer Villwock]
I would hope so, because what we see in the context of immunotherapy for people is that, yes, we do see that there are changes in the nasal microbiome in response to immunotherapy as we've talked about more IL-10 and other of these anti-inflammatory cytokine, but some of the interesting results have also been that, well, yes, there's this shift. There's a clear difference between before and after treatment, but things don't necessarily normalize all the way back to your healthy control patients. Potentially either we tested too early.
A lot of these studies have only have tests have reassessed after about a year, but we know that the whole gamut of the immunologic changes takes several years to develop. I do think that it would be interesting to be able to say, "Hey, we know that your microbiome is slowly shifting towards the normal side, but it's not all the way there yet." To your point, maybe that's where different interventions can be done in terms of topical probiotics or other potential support mechanisms to say, let's keep trying to push that microbiome towards what seems to be a more healthy diversity and proportion of these different bacteria.
[Dr. Ashley Agan]
You had mentioned that immunotherapy, it affects the microbiome in a positive way. Is that for sublingual and subcutaneous equally? Is there a difference? Does one do it better than the other?
[Dr. Jennifer Villwock]
I don't think one does it better than the other. Most of the studies, again, show that we're in equipoise between sublingual and subcutaneous in terms of all of the different ways that they're immunologically mediating allergy, as well as the symptoms that patients have. For the most part, the main distinction between the two is route and if they're going to be able to adhere to the treatment. I always tell folks, "The immunotherapy that's best for you is the one that you can do." If you're the person that's going to be able to come into the office every week and that's your preference, subcutaneous is what's typically going to be covered by insurance.
If that's the route that you need to go and you can commit to that, great, you should do that. If you want to go the sublingual route, there's two different options. There's the FDA-approved sublingual tablets, and those are done at home per the protocol. Those may or may not be covered by insurance because they're FDA-approved. It's one of those like, well, I don't want to co-pay and blah, blah, versus our sublingual aqueous immunotherapy, which we have to counsel folks that, technically this is off label. It's not FDA-approved. It's been used for decades, but it will not be covered by your insurance. Then here would be your out-of-pocket cost. I present folks with all of those options because it's whatever works best in the context of their life in terms of what they can commit to for that three to five years.
Podcast Contributors
Cite This Podcast
BackTable, LLC (Producer). (2025, February 25). Ep. 212 – Allergy Immunotherapy & The Microbiome [Audio podcast]. Retrieved from https://www.backtable.com
Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.
Podcasts
Articles
Factors That Shape Your Microbiome & Sinus Health: Diet, Environment & Probiotics
Allergic Fungal Rhinosinusitis Treatment: Clearing Out the “Peanut Butter”
Evaluating Allergic Fungal Rhinosinusitis (ARFS): Symptoms & Diagnostic Criteria