IBS is a complex, heterogenous disorder meaning that – not every case looks the same. As research progresses, we realize, IBS diagnoses will likely be divided into subtypes dependant on what could be the underlying driver in that individual. Interestingly in practice, I can already say – chances are, you probably won’t just fit into one subtype. Why? It appears that many of the subtypes will have overlapping features, and even influence one another.
Current IBS subtypes proposed include:
- Disorder of gut-brain interaction
- Immune / inflammation driven
- Functional (related to digestion/motility)
- The gut microbiome
Today we’re going to be talking about the current state of understanding on how the immune system may be involved in certain IBS cases.
Our gut’s immune system
Did you know, 70% of our immune system is found in our gut? Our immune system is responsible for not only reacting to invaders, but also recognizing dietary components as safe. When this normal balance is disrupted, our immune system experiences something called ‘loss of tolerance’. This loss of tolerance causes the immune system to react inappropriately to things that it shouldn’t, driving inflammation, altering secretions, peristalsis, and gut permeability, and increasing visceral hypersensitivity.
One way this may occur is through activating mast cells in the gut.
Mast cells are like our storage house for immune components. When your body recognizes something as an ‘invader’ – these mast cells degranulate, releasing compounds, like histamine.
Histamine is an important signalling molecule, driving an inflammatory reaction, altering gut permeability, and also acting like a neurotransmitter – in theory, ‘irritating’ your nerve endings to send signals of pain. It’s important to know – histamine is a normal and important part of our health. However, when we release too much, too often, it can lead to a cascade of negative events.
Histamine in IBS
Histamine is an interesting topic in IBS. It appears that in some IBS models, both human and animal, we can see an increase in total mast cells in the gut. However, this finding is inconsistent. Researchers have also found that those with IBS can ‘degranulate’ more mast cells than healthy controls, and that these mast cells are closer to the nerves in our gut, possibly contributing to an increase in ‘irritating’ the nerve endings.
Does our Gut Microbiome Influence Histamine Release?
In addition, our microbes also play a role in the production and degradation of this compound – possibly implicating the gut microbiome as a driver of too much histamine circulating in the gut.
Another proposed mechanism is that certain individuals with IBS may develop injury to the gut from by-products of microbial fermentation. When our gut microbes ferment foods, like FODMAPs, they produce short chain fatty acids – which are important compounds for our health. However, it has been hypothesized that the microbiome may lead to excessive fermentation and production of short chain fatty acids, excessively lowering the pH, and triggering the microbes to produce ‘LPS’ – an endotoxin that can be injurious to our gut lining. While an interesting hypothesis – this has yet to be explored in humans, and if found, is likely very microbiome-specific.
How does the immune system ‘lose tolerance’?
It’s often said, genetics loads the gun, environment pulls the trigger. Environmental triggers are a likely culprit of changes to our immune system. They can range from dietary changes, to gut microbiome changes, to things like infections. In fact, in animal models, this has been demonstrated with post-infectious IBS.
It is thought that conditions like post-infectious IBS are, in part, driven by a hypersensitization of the immune system in the gut. This hypersensitization has been thought to lead to the loss of tolerance to dietary components, triggering an immune cascade.
Researchers have begun to explore this in the IBS population. In fact, in one study, researchers looked at over 100 patients with IBS and measured their gut permeability in response to common dietary antigens. Remember – antigens aren’t necessarily a bad thing if our immune system handles them properly, they can become a problem if we’ve experienced ‘loss of tolerance’.
The researchers found that exposure to foods high in dietary antigens increased intestinal permeability and eosinophil degranulation. Approximately 60% of the patients reacted to the antigens in wheat, with the second most common reaction being to yeast (20%). The other reactions to milk, soy, and egg, were quite low (9%, 7%, 4%, respectively). While this study was small, it demonstrated that dietary antigens may play a role in IBS symptoms by way of the immune system – something not seen before!
How does immune mediated IBS get managed?
Because research is still in its infancy, there is a LONG way to go before we have specific, evidence-based ways to manage inappropriate immune system reactions.
However, there are a few things we’re already able to explore with patients in practice!
Dietary Changes – The Low FODMAP Diet
Diet is a clear driver of immune response in IBS. The question is – which diet? In our practice, we often start with a ‘low FODMAP diet’. It is one of the most evidence-based way to help manage IBS, and while we don’t really know yet how FODMAPs may drive immune response in humans, if we’re able to manage your symptoms with an approach that works – that is the best place to start.
Dietary Changes – Reducing Dietary Sources of Histamine
If histamine degradation and release is a contributor, it would make sense that lowering foods naturally high in histamine, or that trigger histamine release could be a viable option.
In practice, there are times where I suspect a patient may be intolerant to histamines, and we may trial a short course of a lower histamine diet. A low histamine diet should NOT be combined with other dietary restrictions unless absolutely necessary. I see a lot of crazy things out there layering FODMAPs with low histamine, with additional restrictions on top of that! This is often NOT an appropriate approach, leading to food fears, unnecessary restriction, and many times, not a very significant improvement in symptoms!
A low histamine diet is not a no-histamine diet. The goal is to reduce, not eliminate. In addition, most resources online are contradictory and inaccurate. Working with a dietitian specialized in unusual allergies and intolerances is key to doing this safely. We have a great low histamine menu plan and handout for those looking for accurate information on the low histamine diet. You can read more about Nutrition for Histamine Intolerance here.
Dietary Changes – Reducing Dietary Antigens
Dietary antigens may play a role in some patients IBS. In fact, many IBS patients report that certain foods that we wouldn’t expect bother them. In practice, I often question things like non-celiac wheat sensitivity (NCWS) if a patient finds, despite trying through proper reintroduction strategies, that wheat bothers them. In my Let’s Gut Real interview with Dr. Ali Rezaie we talk about NCWS, and you can read more about it here on our blog.
Many times, medications we would use to manage IBS have the potential (still needs to be researched though!) to have overlapping benefits in immune mediated IBS. Examples of these include:
while the antibiotic, rifaximin is approved for the use of IBS-D and SIBO, we don’t fully understand the mechanisms in which it helps. One potential reason is, with total reduction of microbes in the small bowel, it may reduce the hypothesized impact of microbes that release histamine, and components like LPS which can impact our gut barrier function and immune system. This is hypothetical, but plausible and more research is needed.
Antihistamines and Mast Cell Stabilizers
Specifically, when a histamine intolerance is suspected, certain medications like antihistamines and mast cell stabilizers may be explored with your physician. These medications help by preventing the release of histamine, thereby reducing symptoms.
Stress & Immune Mediated IBS
Stress is often forgotten about in the role it plays in our immune system. Stress is a major contributor to immune system function, and mast cell degranulation. More stress? More dysfunction. Stress is often the cornerstone of managing conditions like histamine intolerance and IBS. In IBS specifically, we know stress and the gut-brain connection play a significant role. Working with your doctor on coming up with a psychology plan is important – whether that’s involving a psychologist, considering gut-directed hypnotherapy, mindfulness-based stress reduction, or potentially adding medications like neuromodulators.
The key takeaway here is that stress management is the cornerstone to managing your GI condition, whether the immune system is involved or not.
Should I be worried about how my immune system is impacting my IBS?
I wanted to present this data in as simple of a way as possible. And in doing that – some of the nuance is lost.
What is IMPORTANT to note is, at this point – we understand and can agree upon the likelihood that a subset of those with IBS do have inappropriate activation of their immune system. But chances are, not all.
Secondly, many of the interventions offered in IBS by way of dietary therapy, psychological intervention, and medication actually help to tackle some of these issues already!
While we don’t have readily available tests available yet to tease out how your immune system is involved and which environmental components (because chances are, it’s not just food!) trigger it, many of the dietary interventions that exist to help explore how these food components make you feel.
Bottom Line: Working with your health care team is your BEST BET for managing this by way of diet, medication, and stress management strategies.