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Mast Cells, Gut Function, and Autism: The Digestive Puzzle

At our clinic, it is common for individuals with autism to also present with concurrent gut issues. While this article is not focusing on the diagnosis of autism spectrum disorder (ASD), it's worth mentioning that it is also common for individuals to go through their entire childhood and adolescence without receiving a diagnosis of autism - especially if they have more mild symptoms or have high intelligence - despite them having symptoms and struggles consistent with autism. Parents and family may even be in denial that their child or loved one does indeed have autism and that their life trajectory might look differently.

An integrative approach to helping someone with autism includes involving family, discussing expectations openly together with compassion, and coming up with a holistic plan that involves helping the individual thrive and working together to improve their health. People with autism can often struggle with mood dysregulation, anxiety, rigid thinking, OCD, anger, sleep issues, and gut issues. Today, I am going to focus specifically on a common connection I see among patients: A connection between autism, gut function, and mast cells.

Mast Cells & the Gut

Mast cells are not just limited to areas commonly associated with allergies, like the skin. They are widely distributed throughout the body, including the gut lining. When activated, these mast cells release mediators, such as histamine, which can have various effects on gut function:

  • Altered Gut Motility: Histamine can influence the rate at which food and waste move through the intestines, potentially causing diarrhea or constipation.

  • Increased Gut Permeability: Mast cell mediators might contribute to a 'leaky gut', where the intestinal barrier becomes compromised. This can lead to harmful substances entering the bloodstream, which might trigger immune responses.

  • Inflammation: Chronic activation of gut mast cells can result in localized inflammation. This can disrupt the gut's normal function and could be implicated in conditions like Irritable Bowel Syndrome (IBS).

Autism, Mast Cells, and the Gut: The Triad

It's widely acknowledged that many individuals with autism experience gastrointestinal (GI) issues. This isn't merely coincidental. Here's how mast cells fit into the puzzle:

  • Gut Symptoms and Behavior: The GI discomfort due to mast cell activity can manifest as behavioral changes in those with autism. A child or adult might not have the ability to express the physical discomfort they're feeling verbally, so it comes out as increased irritability, aggression, or other behavioral changes.

  • Inflammation & the Brain: The inflammation in the gut can lead to increased levels of circulating inflammatory molecules that can impact the brain, potentially exacerbating autism symptoms.

  • Altered Microbiome: There's increasing evidence linking an imbalanced gut microbiome to autism. If mast cell activation affects gut function, it could also be influencing the balance of beneficial vs. harmful bacteria in the intestines.

Immune Dysfunction & Mast Cells

Autism has been linked to immune system dysregulation. Mast cells, being part of the immune system, play into this narrative:

  • Autoimmune Connections: Some theories suggest that autism might have an autoimmune component, where the body's immune system mistakenly attacks its tissues. Mast cell activation could contribute to this by releasing substances that exacerbate immune responses.

  • Cytokine Release: Apart from histamine, mast cells release cytokines — proteins vital for cell signaling. Chronic cytokine release can disrupt regular immune function, further adding to the complexities of autism.

Mast Cell Activation Through the Mental Health Lens

From a mental health viewpoint, potential symptoms pointing toward mast cell involvement in autism encompass:

  • Heightened Stress Sensitivity: Disproportionate responses to stress, leading to over-agitation or withdrawal.

  • Mood Swings: Rapid and intense mood changes without obvious triggers.

  • Sensory Overwhelm: Elevated sensitivity to stimuli, causing emotional distress.

  • Cognitive Difficulties: Challenges with concentration, memory, or processing beyond standard autism symptoms.

  • Allergic Symptoms: Increased occurrences or intensified reactions to allergens.

Diagnosing Mast Cell Activation in Autism

Though the diagnosis of mast cell activation is primarily clinical, based on symptom presentation and history, certain tests can aid in the process:

  • Blood Tests: To check for raised tryptase levels, indicative of mast cell activity.

  • Allergy Tests: Identifying potential allergens that might be triggering the mast cells.

  • Histamine Levels: Elevated levels can indicate increased mast cell activity.

Additionally, at Driftless Integrative Psychiatry, patients are often provided with a screener designed to capture symptoms indicative of mast cell activation, helping in the assessment and subsequent clinical diagnosis.

Mast Cell & Gut Dysfunction Treatment in Autism

While understanding the connection between mast cells, gut dysfunction, and autism is pivotal, translating this knowledge into therapeutic interventions is equally crucial. Through the functional medicine lens, a holistic, patient-centered approach aims to address the root causes rather than just symptomatic relief.

Mast Cell Treatment in Autism

  1. Dietary Interventions: Certain foods are known to trigger mast cell activation. A low-histamine diet might be beneficial, reducing the intake of histamine-rich foods and drinks. Functional medicine emphasizes individualized nutrition, taking into account unique sensitivities and nutritional needs.

  2. Natural Compounds: As suggested by some research, substances like the flavonoid luteolin may inhibit mast cell activation. Quercetin, another natural compound, has also shown potential in stabilizing mast cells.

  3. Medications: Drugs like antihistamines can help counteract the effects of excessive histamine release. Cromolyn sodium is another medication that stabilizes mast cells, preventing them from releasing their inflammatory mediators. Low dose naltrexone is also a known mast cell stabilizer.

  4. Stress Management: Chronic stress can trigger mast cell activation. Integrative approaches, such as mindfulness meditation, deep breathing exercises, and yoga, can be useful in managing stress.

Addressing Gut Dysfunction in Autism

  1. Probiotics & Prebiotics: Restoring a balanced gut microbiome is crucial. Probiotic supplements introduce beneficial bacteria, while prebiotics, like dietary fiber, serve as their food source, promoting a healthy gut environment.

  2. Digestive Enzymes: Some individuals with autism may benefit from enzyme supplementation to aid in the breakdown of specific food components, potentially reducing gut discomfort and improving nutrient absorption.

  3. Elimination Diets: Functional medicine often employs elimination diets to identify and remove potential food triggers, which could be exacerbating gut symptoms and influencing behavior.

  4. Bone Broth & Collagen: These are believed to help seal the gut lining, potentially addressing the "leaky gut" syndrome. They provide essential nutrients and amino acids that support gut health.

  5. Anti-inflammatory Supplements: Omega-3 fatty acids, turmeric, and ginger are examples of supplements that can help reduce inflammation in the gut.

The Functional Medicine Perspective

From the functional medicine viewpoint, every individual is unique. What works for one might not work for another. It emphasizes the importance of:

  • Personalized Treatment Plans: Individual genetics, environment, and history guide treatment decisions.

  • Root-Cause Approach: Instead of just treating symptoms, functional medicine seeks to identify and address the underlying causes.

  • Integrative Care: Incorporating traditional medical approaches with alternative and complementary therapies, such as nutritional therapy, acupuncture, or herbal medicine.


Addressing mast cell activation and gut dysfunction in those with autism requires an all-encompassing approach. Current research, combined with a functional medicine perspective, offers promising strategies. As our understanding deepens, treatment modalities will likely become even more refined, further enhancing the quality of life for those on the spectrum.

Further Reading Resources

Theoharides, T. C., Asadi, S., & Patel, A. B. (2013). Focal brain inflammation and autism. Journal of Neuroinflammation, 10(1), 46.

  • Overview: This article dives into the evidence suggesting brain inflammation plays a role in the pathogenesis of autism and the involvement of mast cells in this process.

Margolis, K. G., Buie, T. M., & Turner, J. B. (2016). Gastrointestinal Symptoms and Autism Spectrum Disorder: A Literature Review. Autism Research, 9(5), 493-507.

  • Overview: A comprehensive review detailing the correlation between gastrointestinal issues and autism, highlighting the need for further research in this domain.

Frieri, M. (2013). Mast cell activation syndrome. Clinical Therapeutics, 35(5), 584-589.

  • Overview: This article provides insights into mast cell activation syndrome, its symptoms, and potential treatment approaches.

Naviaux, R. K. (2018). Metabolic features of the cell danger response. Mitochondrion, 41, 147-156.

  • Overview: Explores the cell danger response and its potential connection to diseases like autism, and how metabolism plays a role in this.

Björkstén, B., Sepp, E., Julge, K., Voor, T., & Mikelsaar, M. (2001). Allergy development and the intestinal microflora during the first year of life. Journal of Allergy and Clinical Immunology, 108(4), 516-520.

  • Overview: Discusses how the intestinal microflora in early life might influence the development of allergies, a concept potentially applicable to mast cell activation and autism.

Institute for Functional Medicine. Functional Medicine Approach.

  • Overview: A comprehensive resource detailing the principles and approaches of functional medicine.

Ballaban-Gil, K., & Rapin, I. (2002). Autism and the gastrointestinal tract. American Journal of Psychiatry, 159(9), 1481-1484.

  • Overview: Investigates the ties between autism and the GI tract, providing a foundational understanding of this connection.

This blog post is designed as a general guide. This is not a substitute for personalized medical advice, nor is a patient-physician relationship established in this blog post.


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