Part 4: Autism and Health Issues Unpacked: Exploring the Intersection of Autism and Chronic Fatigue Syndrome

Written by Claire Eliza Sehinson, MS with Dr. Megan Anna Neff, PsyD. Originally posted on Neurodivergent Insights

This is a continuation from Part 3.

IBS (Irritable Bowel Syndrome) and Its Intersection with CFS/ME and Autism

IBS is frequently seen within the context of CFS/ME, with an estimated 30-90% overlap, and autism, where Autistic children are four times more likely to experience gut issues (McElhanon et al., 2014). IBS is often a diagnosis of exclusion, meaning, the diagnosis is used when a range of gut and digestive symptoms cannot be explained by objective medical tests.

The Gut-Brain Axis

The bi-directional relationship between the gut and the brain, primarily through the vagus nerve, offers a holistic view of how emotions can affect gut function and vice versa. This connection is crucial in understanding the interplay between mood, cognition, and gut health. A large Randomized Controlled Trial (RCT) demonstrated that gut-directed hypnotherapy positively influenced both physical and psychological symptoms in IBS patients and was even more effective than a low-FODMAP diet for psychological symptoms (Peters et al., 2016).

Interoception, Insular Dysfunction, and IBS

Both impaired interoception and insular dysfunction (a disruption in the brain region involved in emotional and sensory processing), prevalent in Autistic individuals, are also central to IBS. These factors can influence gut function in various ways (Bonaz et al., 2021), including:

Increased sensitivity to digestive pain.
Heightened reactions to ingested substances unrelated to the immune system (e.g., non-allergic food sensitivities).
Abnormal sensory processing of food characteristics.
Challenges in regulating appetite, satiety, toileting needs, or thirst.
Emotional or stress responses manifesting as hunger, fullness, stomach aches, or bloating.
Elevated markers of digestive and neuro-inflammation.

Gut Inflammation and IBD: Links to CFS/ME and Autism

Inflammatory bowel diseases (IBD), such as Crohn's Disease and Ulcerative Colitis, have a notable connection with Chronic Fatigue Syndrome (CFS/ME). Individuals with IBD are at an increased risk of developing CFS/ME (Tsai et al. 2019). Similarly, substantial research in Autistic children has linked their gut symptoms to underlying inflammatory bowel conditions (Lee, 2018).

The Gut-Brain Connection and Mood Disorders:

There is robust evidence that mood disorders, including depression, anxiety, and fatigue, are associated with inflammation and immune system activation (Lee, 2018). This link further underscores the critical gut-brain connection and opens promising avenues for support and investigative options for people experiencing fatigue and mood challenges, regardless of either a diagnosis of CFS/ME or autism.

Gut Dysbiosis & Parasites: Impacts on Immunity and Chronic Conditions

Our gut houses 70-80% of the immune system, making the balance of gut bacteria critical for immune function and metabolic health. Dysbiosis, an imbalance between beneficial and harmful gut bacteria, has been a focal point in understanding the link between diet, gut health, and various chronic conditions, including Long-COVID (UCLA article 2021).

Large-scale studies, such as ZOE, have shown that fiber-rich diets increase microbial diversity and the presence of key species that produce anti-inflammatory and immune-boosting chemicals. This can lead to a healthier gut environment, reduced gastrointestinal complaints, and improved physical and mental health outcomes. It also positively influences metabolic responses to food, like blood sugar regulation, helping to prevent conditions like type II diabetes (ZOE, 2023).

Research on the gut microbiome in CFS/ME patients, particularly regarding neurological and mood symptoms, has found reduced microbial diversity, higher amounts of pro-inflammatory species, and fewer anti-inflammatory bacteria (Giloteaux et al., 2016).

In the context of autism, reduced microbial diversity has long been associated with gastrointestinal issues. Innovative treatments, such as Fecal Microbial Transplant (FMT), have been explored. In a clinical trial, Autistic participants (with significant support needs) receiving FMT showed improvements in motor skills, GI symptoms, and a variety of behavioral aspects up to two years post-treatment (Kang et al., 2019). However, the exact link between the gut microbiome and autism is still debated. Notably, studies like Yap et al. (2021) suggest that restricted eating patterns and dietary preferences common in autism might contribute to reduced microbial diversity and GI symptoms.

Gut Hyper-Permeability (Leaky Gut) and intestinal barrier dysfunction

Our intestinal barrier is a complex barrier and our first line of defense against toxic substances we may ingest. It is made up of many types of functional cells held together by “tight junction proteins” - a bit like bricks in a wall held together by cement. The gut has to allow water and nutrients from our food into our bodies whilst keeping out the “bad guys” - pathogens such as bacteria, viruses and toxins. Immune cells like mast cells and lymphocytes are stationed close to this barrier to neutralize any potential threats.

What is Leaky Gut?

Gut hyper-permeability, or "leaky gut," occurs when the gut barrier becomes more permeable than usual, allowing particles that don't normally enter our bodies to pass through. This can be due to several factors, including autoimmune attacks on tight-junction proteins or inflammatory responses from infections. When substances like large food proteins or chemicals enter the bloodstream, the immune system recognizes them as foreign, and mount an attack as if it was a dangerous infection or an allergen resulting in inflammation and/or multiple food intolerances that can affect many systems in the body simultaneously.

Markers of leaky gut are linked with digestive issues, inflammatory bowel conditions, food allergies, and related disorders like eczema or asthma. However, it's still debated whether leaky gut is a cause or an effect of these conditions.

Leaky Gut and Chronic Fatigue Syndrome

In CFS, leaky gut has been correlated with illness severity, cognitive difficulties, muscle tension, and irritable bowel (Maes, 2007). A notable study by Maes and colleagues found that addressing weakened gut barriers and dysbiosis in CFS patients led to significant improvements or complete remission of symptoms.

Leaky Gut in Autism

Likewise leaky gut is also implicated in Autistic people. One study found 36.7% of Autistic children had higher intestinal permeability compared to less than 5% of allistic children. Autistic people also have higher rates of food intolerances, allergies and multiple chemical sensitivities all of which are complications that arise from intestinal barrier dysfunction.(Dargenio, et al., 2023)

The take home message is gut issues coexist with autism and CFS in complex ways. Research demonstrates bi-directional mechanisms between the gut and the brain. Whilst it is unlikely to cause either condition, much of the symptoms associated with distress, suffering, fatigue, pain and IBS could be alleviated and modified when examining these links.

SIBO & Gut Motility Issues

Small intestinal bacterial overgrowth, or SIBO, is a condition detected in up to 80% of people with IBS and is also associated with a wide range of chronic conditions, including CFS and autism.

Understanding SIBO

SIBO occurs when bacteria, typically found in the large intestine, overgrow in the small intestine – the primary site for digestion and nutrient absorption. This overgrowth leads to bacteria fermenting food, producing gases like hydrogen and methane, and other byproducts like histamine. The result can include upper digestive symptoms such as bloating, pain, cramping, diarrhea, or constipation, along with widespread inflammation and various body and brain symptoms.

Symptoms often appear within 90 minutes of eating, especially after consuming high FODMAP foods that bacteria readily ferment, like onions, cauliflower, chickpeas, lentils, and garlic.

Consequences of SIBO

The inflammation from SIBO can lead to malabsorption and nutritional deficiencies. For instance, iron deficiency anemia is common among those affected.

Complexities in SIBO Development and Treatment:

Understanding and treating SIBO is complex, and the condition is known for being difficult to manage and prone to recurrence. Our current understanding suggests that SIBO is a motility disorder. The autonomic nervous system controls peristalsis (contractions moving food through the digestive tract) and the migrating motor complex (MMC), which are critical for preventing bacterial buildup in the small intestine. These processes are regulated by the vagus nerve, and any impairment in vagal motor outflow can lead to disorders like SIBO and constipation.

Psychological stress, anxiety, and trauma, known to affect vagal tone, are also believed to play a role in SIBO, particularly in cases that are recurrent or resistant to treatment.

Mast Cell Activation & Histamine Intolerance

Histamine, a key chemical and neurotransmitter, plays diverse roles in our immune, digestive, cardiovascular, and nervous systems. Histamine intolerance (HIT) occurs when the body's capacity to break down histamine is compromised, leading to an accumulation. Due to the wide distribution of histamine receptors, HIT can cause a variety of symptoms throughout the body such as:

Skin Reactions: Including hives, itching, and rashes.
Digestive Issues: Such as diarrhea, nausea, vomiting, and abdominal cramps.
Respiratory Problems: Including nasal congestion, sneezing, asthma, and difficulty breathing.
Neurological Symptoms: Such as headaches, migraines, dizziness, and fatigue.
Cardiovascular Effects: Like irregular heartbeats, blood pressure changes, and flushing.
Mental Health Impacts: Including anxiety, difficulty sleeping, and irritability.
Allergic Reactions: Ranging from mild sensitivities to severe allergies. (Reference: Maintz & Novak, 2007).

Histamine Intolerance (HIT)

Histamine Intolerance (HIT) occurs when the body struggles to break down histamine efficiently. This condition can arise from a deficiency in histamine-degrading enzymes:

Diamine Oxidase (DAO): This enzyme is found in the mucosal linings of the gut, lungs, and uterus.
Histamine N-Methyl-Transferase (HNMT): This enzyme works inside our cells.

These deficiencies might be genetic or stem from other issues like inflammatory bowel disease or leaky gut, which reduces DAO's available surface area. Additionally, menopause can significantly decrease DAO production in the uterus.

External Sources of Histamine:

Histamine can also be produced by some strains of gut bacteria and is present in a large number of foods in our diet - both of which can add to the bucket load.

Hormones and Histamine

Oestrogen and xenoestrogens (natural or synthetic chemicals that mimic estrogens in the body) are also found to lower DAO and trigger mast cells to release histamine. The natural ebb and flow of hormones during the menstrual cycle can add additional histamine challenges at different times.

*** Clinically we observe that some patient’s will notice their HIT symptoms get worse around certain points in their cycle or the period where they first experienced HIT may coincide with peri-menopause.

Mast Cell Activation

Histamine and various other chemicals are stored and released from mast cells. Mast cells are part of our first line immune response. They also act as sensors of stress and danger being strategically positioned or surfaces that interface the “outside world” such as our skin, gut lining, airways and the blood-brain-barrier so that any pathogens are dealt with before they have a chance to enter.

What is also intriguing is that mast cells release a hormone called Corticotropin Releasing Hormone which induces the production of cortisol from the adrenal gland. So mast cells induce stress but stress and fear in turn activate mast cells in a vicious cycle. This association was described by Theoharides and his group in Autistic children.

Mast Cell Triggers

Mast cells can be activated by various factors, including allergens, infections, certain drugs and medications, hormones, endorphins, toxic metals, IgE/G antibodies, histamine-rich foods, and physical stress (i.e. exertion from strenuous exercise or cold/heat stress or sudden temperature changes).

Mast cells develop a 'metabolic memory,' becoming more sensitized and reactive over time. Mast Cell Activation Syndrome (MCAS) occurs when mast cells become unstable and are easily triggered, often requiring minimal stimulation.

MCAS and HIT

Approximately 20% of people with histamine intolerance will also have MCAS, however they are not the same condition and working with MCAS is a more complex process. MCAS is one of thefeatures of immune dysfunctionand is believed to play a role in Long-COVID andME/CFS.

Methylation (Epigenetics and Genomic SNPS)

The Role of Methylation in Cellular Function

Methylation, a critical biochemical process in every cell, has profound implications in various health conditions. It has long been discussed in health research including autism, heart disease, cancer, hormone imbalances, fertility, and chronic illnesses.

Epigenetics and Methylation

One of the most pivotal roles of methylation is in epigenetics - the study of how gene expression is regulated by external and environmental factors without altering the DNA sequence. Methylation acts as a molecular switch that can turn genes on or off, a process crucial for normal development and cellular differentiation. This means that while our DNA provides the blueprint, methylation patterns determine how, when, and to what extent these instructions are used.

One of the landmark studies to demonstrate this was the Dutch Hunger Winter study. Pregnant people exposed to famine and stress during this period had descendants, even multiple generations later, with higher rates of metabolic conditions (cardiovascular disease, diabetes), neurodegenerative diseases, poorer cognitive function, increased breast cancer risk, overall cancer mortality, and symptoms of anxiety and depression.

Furthermore, Dr. Moshe Syzf's research in "social epigenetics" explores how early life adversity and trauma can be inherited intergenerationally through DNA methylation.

Methylation, SNPs, and Personalized Health

Methylation's role in health is further complicated by genetic variations known as single nucleotide polymorphisms (SNPs). Variations in genes involved in the methylation process can influence how effectively these mechanisms work, potentially predisposing individuals to various health conditions.

Autistic people and CFS patients (as well as host of other chronic health conditions) are found to have higher methylation deficits due to variations of some key methylation genes such as the MTHFR (methylenetetrahydrofolate reductase) 677T gene. These genes express “methylation enzymes” that perform these chemical reactions. So having variations in these genes means methylation processes in the body can run more slowly than usual.

Our methylation capacity depends on key nutrients such as folate, B12, B6 and betaine, all of which can be obtained from our diet. However the MTHFR 677T snp (associated with chronic health issues) means these nutrients cannot be “activated” to the form needed in our cells.

Importantly methylation is a key area of excitement for practitioners due to available nutrigenomic testing and dietary, lifestyle and supplement protocols that can be applied. However we caution with over-supplementation or self-prescribing as methylation requires balance and many people’s experience of using active or high strength supplementation is a worsening of their symptoms as over-methylation can have negative consequences too. So it is always advisable to work with a functional medicine or nutritional therapy practitioner for personalized guidance.

Understanding Hypermobility

Having joint hypermobility(often referred to as being “double-jointed”) means that your joints have a larger than normal range of movement due to the laxity of the ligaments and structures of the joint capsule. This increased movement, can lead to instability. People can be hypermobile in just one joint or multiple joints around the body (and there are over 350 in the human body!)

Hypermobility is often a genetic predisposition but it can also occur following trauma or injury (i.e. a dislocated shoulder) or secondary to a connective tissue disorder or autoimmune condition such as Lupus.

Ehlers Danlos Syndrome

EDS encompasses a group of inherited connective tissue disorders, with 13 known subtypes. Most are marked by varying degrees of joint hypermobility, with hypermobile EDS (hEDS) being the most common. This involves an inherited issue with collagen production, the most abundant protein in the body. Collagen is vital for providing strength and support in the musculoskeletal system and adds 'stiffness' to structural tissues.

This stiffness gives integrity to structures such as our gut (in order for us to have normal motility and bowel transition) and our arteries (in order for us to keep our blood pressure up and pump blood to our brain). Our eyes, skin, heart valves and uterine lining are all composed of collagen too. So when we have a collagen disorder, we can experience a wide array of symptoms.

Hypermobility in CFS and Fibromyalgia

Studies indicate that up to 81% of individuals with CFS and Fibromyalgia meet criteria for hypermobility syndromes (Eccles et al., 2021). Additionally, people with EDS are significantly more likely to be Autistic (7 times) and to have ADHD (6 times) compared to the general population (Csecs., et al 2022).

Brain Imaging Studies

Compelling brain imaging studies found that people with hypermobility often have larger fear processing centers in the brain. This finding aligns with the prevalent mental health conditions observed in both Autistic and CFS populations, highlighting a potential neurological basis for these overlapping experiences.

Dysautonomia and POTS (Postural Orthostatic Tachycardia Syndrome)

Understanding Dysautonomia

Dysautonomia is the inability of your autonomic nervous system to regulate itself, which includes involuntary functions such as blood pressure, heart rate, body temperature, blood sugar levels or breathing patterns. With dysautonomia the communication between your autonomic nervous system and the rest of your body is out of sync which results in great difficulties in adapting to or regulating yourself for example if the room temperature changes, adjusting from sitting to standing positions or energy levels if you haven’t eaten anything for a few hours. The effects can range from mild to severe.

Dysautonomia can be hereditary (rare) or develop secondary to other health issues, including neurodegenerative diseases (like Parkinson's), central nervous system infections (such as CMV, Lyme, and COVID), traumatic brain injury, autoimmune disorders (like M.S., Lupus), vitamin B1 or B12 deficiencies, Ehlers Danlos Syndrome, mitochondrial diseases, and many more.

POTS: A Common Form of Dysautonomia

POTS (postural orthostatic tachycardia syndrome), one of the most prevalent types of dysautonomia, is often identified by a rapid increase in heart rate upon standing, accompanied by symptoms like dizziness, a "head rush," or fatigue.

Mechanism Behind POTS

In POTS, the autonomic nervous system struggles to adapt quickly enough when moving from sitting or lying down to a standing position. Normally, blood vessels need to contract swiftly to send blood and oxygen to the brain. However, in POTS, this response is delayed, making the heart work harder to pump blood upwards, resulting in tachycardia (rapid heart rate) or symptoms like faintness, dizziness, or fatigue due to reduced oxygen flow.

POTS in CFS, Chronic Illness, and Autism

POTS is commonly observed in individuals with CFS, chronic illnesses, and Autistic people. Management often includes increasing salt and fluid intake to boost blood volume. Functional medicine practitioners also seek to identify and address underlying causes, which can range from supporting hypermobility issues to resolving infections affecting cranial nerves, to improve autonomic nervous system function.

continued in part 5

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Autism, Chronic healthKiley HanishAugust 3, 2024