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July 10, 2023

Asthma, Allergies and Nutrition - The Story

Here is a long form look at asthma and allergies as I am preparing a lecture on asthma and allergies for a conference in October. I will break it up into a few parts for your consumption.

  • Asthma is now well known to be an inflammatory disease based on the response to anti-inflammatory medications and pathophysiological evidence making it a prime candidate for anti-inflammatory nutritional interventions. 
  • The Standard American Diet is filled with pro-inflammatory highly refined and processed foods that are laden with excessive amounts of sugar and unhealthy fats thus promoting inflammatory pathways that exacerbate disease.
  • The genesis of the inflammation is now believed to start in part in the intestinal and pulmonary microbiomes with the loss of immune tolerance. The intestinal microbiome is highly responsive to whole food dietary alterations. 
  • Uric acid, a by product of fructose metabolism, is becoming a known driver of inflammasome activation and local tissue inflammation
  • We will discuss in depth the food choices that lower the inflammatory burden, the asthma phenotype and the food immune reactions that exacerbate disease. 

Historical medical training over the past half century has focused on asthma as an allergic disease that is predominantly only modifiable through allergic trigger avoidance and pharmaceutical medical therapy. Physicians were never trained to focus on diet or nutrition as a tool for disease remediation. Frankly, it was scoffed upon to worry about a patient's sticky bun habit as means to modify their symptoms. However, science has created a new working understanding of asthma as a modifiable disease with the discovery of the epigenome, microbiome, metabonome and nutrigenome. 

In order to understand how food will and does effect asthma, the understanding of the first principles root cause of asthma is critical. Asthma is an inflammatory disease that has its genesis very early in life when a person develops a disruption of immune tolerance. This disruption occurs for many reasons; however, the leading theory is the Biome Depletion Theory which has improved upon the earlier Hygiene Hypothesis that Strachan et. al. discussed in the 1990's.(Stiemsma et. al. 2017) This theory basically states that the loss of co evolving microbes, especially helminths/parasites, has put a strain on the ability of the immune system to develop natural tolerance to non-pathogenic protein epitopes from foods, plants, dust, animals, etc. 

The prototypical study that looked at this reality was published in 2016 and looked at house dust microbial cell wall endotoxin levels in the genocentric communities of the Amish and Hutterite enclaves in the United States. The measured dust endotoxin level was used as a marker of microbial coevolution from birth. The Amish community lived very intimately with their animals as the children spent much time from birth on exposed to animals in their immediate vicinity. Contrast this with the Hutterite community where the children lived peripherally on a mechanized centralized farm. They were rarely exposed to the farm animals. This differential exposure to the animals gave the Amish children a roughly 7 times higher microbial exposure then their Hutterite brethren throughout their lives. Statistically, the study showed that the Amish offspring had a 4X fold lower risk of developing asthma and allergic sensitization. They posited that the lack of microbial exposure was driving the disease in the Hutterite children.(Stein et. al. 2016)

The researchers furthered the evidence of causation and not just association by exposing asthma prone mice to the respective endotoxin laden house dust from both communities. What they found was remarkable. The dust exposure dictated whether a mouse developed the disease phenotype that we call asthma. The Amish dust exposed mice did not develop asthmatic disease paralleling the human data of disease risk.(Stein et. al. 2016) This is a relatively strong data set for causation as the endotoxin exposure leads to natural immune priming and tolerance. The 2 year (2020-22) Covid 19 isolation, masking and hyper sanitizing experiment is an unnatural experiment that we can follow and need to follow for the development of atopic diseases in children based on the lack of endotoxin/infectious exposure. We have seen a massive shift in illness onset from all cause infectious diseases since the fall of 2022 when life returned to pre pandemic activity in North Carolina. Kids are getting infections at frequent and significant morbid levels due to the 2 year immunity debt from these COVID isolation practices. The volume of disease of atopic volume appears higher, but this is purely anecdotal in origin. I am waiting for hard numbers to answer the question. In the next few months, I hope to have some raw data pulled from our EMR to see if a trend has occurred based on the diagnosis of wheeze, asthma or albuterol medicine use.

Knowing that a failure of early microbial exposure is compounded by over clean home environments, cesarean section birth deliveries, antimicrobial drug use and a lack of breastfeeding, the science is now proving that the long-term effect is to develop an abnormal intestinal microbiome that allows the interface between the outside world, i.e. food and the immune system to be compromised. The actual process by which this happens immunologically is beyond the scope of this article.(Stiemsma et. al. 2017) 

Essentially, there is a cross talk between the microbes of our lungs and gut and our immune cells that is disrupted leading to abnormal recognition of food protein epitopes leading to antibody responses primarily in the IgE class as in food allergy and the IgG, IgG4, IgA classes for food sensitivity/intolerance. There is also a solid body of growing evidence that beyond the humoral immune system's response there is an innate immune/T cell response to intestinal and pulmonary microbial peptides driving low grade endotoxemia that is seen as inflammation.(Cani et. al. 2009) 

This latter point is likely a major player in the inflammatory process of humans as it is well known that highly processed foods laden with sugar, high fructose corn syrup and saturated fats drive the intestinal microbiome to a dysbiotic gram negative rod predominant enterotype.(Moreira et. al. 2012)(Stokholm et. al. 2018)(Stiemsma et. al. 2017)(Weng et. al. 2013) Fructose is a special category as it is broken down into the metabolite uric acid which is a known inflamasome activator and leads to localized pulmonary inflammation. We will discuss this further in a week or so.

What is now evolving rapidly is the scientific understanding that beyond the early life risk factors for immune disruption as stated earlier, there is clear evidence that the nutritional components of the human diet dramatically effect what microbes make up the intestinal microbiome.(David et. al. 2014) The diet and lifestyle induced microbial community in turn can increase the risk of low level bacterial endotoxemia and therefore systemic inflammation that we see as worsening of a disease like asthma. 

Following this pathological mechanistic path, the ability to use the nutritional component of human lifestyle medicine is now critical to ameliorating diseases of all inflammatory types including asthma. What are the mechanisms of food induced inflammation? What foods promote the growth of which microbes in the gut? These are the evolving research projects that will elucidate better answers over time. 

How is nutrition in the broader context understood as it relates to disease risk? Breakfast, lunch and dinner have long been the place-time events where humans congregate in fellowship. Food is revered in many cultures for its intrinsic healing properties and also for disease prevention. Modern America, for many reasons, has fallen away from this belief as corporate and government sponsored food distribution services have sought to maximize taste and caloric density over macro and micro nutritient makeup. We have fallen prey to this reality as our taste buds and psyche are evolutionarily geared to love the easily consumed varieties of the macronutrients, carbohydrate, fat and protein, which are the lifeblood of the human energetic model. Providing energy is paramount to survival. (Krebs 2009)(Breslin 2013) 

Moving past this caloric taste-based model of eating and toward a healing food consumption model is predicated on understanding which foods are driving disease. Looking at some recent research in inflammatory bowel disease by Suskind et. al., we see a first design and implementation study to prove the effect of diet on inflammation. His group used a specific carbohydrate diet that is devoid of trigger antigens like casein, gluten and other grain proteins.(Suskind et. al. 2018)

Removing these antigenic triggers to immune sensitization caused a down regulation on innate and adaptive immune attack on the gut lining thus reducing the symptoms and clinical markers of inflammatory bowel disease. 

This immune mechanism response to diet is believed to occur in many inflammatory based disease states like asthma and allergy that are seemingly disparate from autoimmune diseases like Crohn's. The medical allergy community has to date focused only on true IgE mediated food reactions as a means to potential asthma disease avoidance as it relates to food. Yet, Suskind et. al. with the Crohn's model has shown us that what is really happening is multimodal immune mediated responses and not just reduced to one antibody response, IgE. This process is also well visualized in the infants and children suffering from food non IgE mediated disease like milk casein protein intolerance that presents with symptoms of eczema, colitis, gastroesophageal reflux and colic behavior. What is happening immunologically in asthma and allergy?

We need to keep an open mind to the complexity of human immunological responses to food and avoid reductionist medicine that silos disease etiology to one cell type. If there is anything that I have learned over the last 2 decades, it is that reductionist beliefs are mostly wrong. 

The story continues next week,

Dr. M

Stiemsma AACI Article

Stein NEJM Article

Cani Current Opinions Pharmacology 

Moreira British J Nutrition

Stokholm Nature Communications Article

Weng J Develop Origins Health Disease Article

David Nature Article

Krebs American J Clinical Nutrition Article

Breslin Current Biology Article

Suskind J Clinical Gastroenterology Article