September 30, 2019

Autism & the Gut: Are they linked & what is the link? Part 2: Autism, in The Gut-Brain Axis Series

by Nicola Schuler, CNTP, MNT and Dr. Miles Nichols

Last week’s blog on Autism & the Gut Part 1 covered some facts about ASD as well as some of the contributing factors as they relate to genes and the environment. This week, in Autism & the Gut Part 2, we continue discussing the environmental factors that contribute to ASD, as well as cover gut health and its impact on ASD. Then in Autism & the Gut Part 3, we will outline specific action steps that you can take with diet, supplements and lifestyle habits, to address ASD.

In addition to what we covered last week, such as pre-natal factors, maternal nutrient deficiencies and environmental chemicals, these are Environmental Factors that can contribute to ASD:

  • Endocrine disruptors: These are chemicals that disrupt the endocrine (hormone) system of the body. Exposure to these chemicals pre-natally and in very early life can affect brain development.
    • It is thought that the effect of excessive testosterone on specific brain regions might be a key mechanism to push the brain to an extreme male pattern of more systematizing and less empathizing, which is in line with ASD characteristics (Modabbernia A, 2017). Therefore, factors that alter hormonal balance (and particularly fetal testosterone) might contribute to risk of ASD.  For example, flame retardants are both associated with an increased level of free testosterone and an increased risk of ASD (Modabbernia A, 2017).
    • Recent studies have shown that chemicals associated with lower testosterone levels are also associated with lower risk of autistic behaviors (Modabbernia A, 2017).
    • Another link between endocrine disruptors and ASD is alteration in thyroid function. Several studies have shown evidence of prenatal maternal thyroid dysfunction and ASD in the offspring (Modabbernia A, 2017). Many endocrine-disrupting chemicals that disrupt thyroid hormone function have also been hypothesized to increase the risk of ASD (Modabbernia A, 2017).
    • Studies of phthalate (an endocrine disruptor) exposure showed a significant association between phthalate exposure and risk of ASD (Modabbernia A, 2017).
  • Metals: Heavy metals, such as lead, cadmium, mercury, etc. are established neuro-toxins with documented impacts on cognitive and developmental outcomes (Lyall K, 2017).
    • Studies found an association between heavy metal concentration (mostly mercury and lead) and severity of ASD (Modabbernia A, 2017).
    • Twelve studies described improvement in symptoms of ASD following chelation therapy (a technique used to remove heavy metals from the body) (Modabbernia A, 2017).
    • In a genetically sensitive individual, toxic metals cause significant oxidative stress. This leads to impaired methylation/processing of folate and alters the capacity for synchronizing neural networks as a result of an impaired dopamine function (Modabbernia A, 2017). This affects epigenetic mechanisms, leading to abnormal gene expression. Both mechanisms, impaired synchronization of neural networks and epigenetic alterations related to methylation, are closely linked to ASD (Modabbernia A, 2017).
  • Glyphosate: Glyphosate is the active ingredient in Roundup Ready, the most widely used herbicide in the world (Samsel A, 2015). Glyphosate is liberally used on core food crops, because it is perceived to be non-toxic to humans. The adoption of genetically engineered “Roundup-Ready” corn, soy, canola, cotton, alfalfa, and sugar beets has made it relatively easy to control weeds without killing the crop plant, but this means that glyphosate is present as a residue in foods.
    • As weeds among GM Roundup-Ready crops are developing ever-increasing resistance to Roundup, use of the herbicide is increasing. In fact, its usage has increased steadily since 1987, in step with the rise in ASD rates (Samsel A, 2015).
    • In one study, the authors wrote: “Despite its relatively benign reputation, Roundup was among the most toxic herbicides and insecticides tested.” (Samsel A, 2015)
    • One paper states that this may explain the recent increase in incidence of multiple neurological diseases (Samsel A, 2015).
    • Glyphosate indirectly affects Lactobacillus, leading to increased anxiety via the gut–brain access (Samsel A, 2015). Both low Lactobacillus levels in the gut and anxiety syndrome are known features of ASD, and Lactobacillus probiotic treatments have been shown to alleviate anxiety and ASD (Samsel A, 2015).
    • Glyphosate indirectly results in mitochondrial damage, a hallmark of many neurological diseases and a factor in ASD (Samsel A, 2015).
    • This is a controversial topic, but glyphosate is frequently named as an environmental factor driving the rise in ASD that we see today.
  • Inflammation & immune system function: ASD is associated with an altered immune status, increased oxidative stress, and inflammation in the brain.
    • Concentrations of pro-inflammatory immune system molecules are increased in patients with ASD compared to those in healthy people (Modabbernia A, 2017).
    • A maternal autoimmune disease can increase the risk of ASD through the effect of maternal inflammatory mediators and autoantibodies on fetal neurodevelopment (Modabbernia A, 2017).
    • Substances such as lead, mercury, pollutants, or perinatal complications can cause inflammation and oxidative damage in the brain, which can impair neural growth and development (Modabbernia A, 2017).
  • Neurotransmitter changes and interference with signaling pathways in the brain: Neurotransmitters (NTs) are chemicals in the brain responsible for signaling. We wrote in some detail about NTs in our article on anxiety.
    • Abnormalities in the NTs glutamate, serotonin and GABA have been linked to ASD (Modabbernia A, 2017).
    • Some of the issues discussed already, like lead, environmental pollutants and flame retardants, disrupt the activities of NTs; NMDA, glutamate and GABA respectively (Modabbernia A, 2017).
    • Some environmental risk factors interact with intracellular signaling pathways and can impair neurodevelopment. For example, exposure to PCB and PBDE (chemicals used in plastics, construction, flame retardants, etc.) seems to alter a signaling pathway, leading to abnormalities in dendritic growth and neuronal connectivity, a key feature of ASD (Modabbernia A, 2017).

Gut health – As we have seen in our previous articles on the Gut Brain Axis (Anxiety, ADHD 1, ADHD 2, ASD 1), the gut microbiome is an important environmental factor that influences symptoms of various conditions, including ASD. Research has increasingly observed that children with ASD have distinctive gut microbiomes compared to neurotypical children (Kang DW, 2019). Thus through the microbiome-gut-brain axis, gut health influences ASD.

Gastrointestinal (GI) symptoms, such as abdominal pain, gas, diarrhea, constipation and flatulence, are common in people with ASD (Li Q H. Y., 2017). Constipation is found to be the most prevalent symptom (85%) in children with ASD (Li Q H. Y., 2017).

Other common symptoms are gut inflammation, intestinal permeability, low levels of digestive enzymes/ poor digestion, reflux esophagitis, impaired detoxification and dysbiosis (Horvath K, 1999). The prevalence of GI symptoms ranges from 23 to 70% in children with ASD (Li Q H. Y., 2017).

It has been found that improvements in GI and ASD symptoms are significantly correlated (Kang DW, 2019). In other words, attaining relief of GI symptoms may improve behavioral severity in children with ASD (Kang DW, 2019).

Dysbiosis, or an imbalance in gut flora with more bad bacteria than good in the gut, has been found in cases of ASD. Diversity, or the variety of gut bacteria found in people with ASD, is about 25% lower than in healthy people (Kang DW A. J., 2017). Their guts are missing hundreds of different species of bacteria, often ones that are important to fermentation and producing short chain fatty acids that influence health (Kang DW A. J., 2017).

For example, the guts of children with ASD exhibit lower levels of Bifidobacterium and Firmicutes and higher levels of Clostridium, Bacteroidetes, Desulfovibrio, Caloramator and Sarcina (Li Q H. Y., 2017). Children with autism who present GI symptoms have lower abundances of the species Prevotella, Coprococcus, and unclassified Veillonellaceae than that found in GI symptom-free neurotypical children (Li Q H. Y., 2017).

Clinical trials using fecal microbiota transplants (FMT) have shown promise with ASD. One trial using high-dose FMT for 1-2 days and then 7-8 weeks of highly purified oral solution dosing found significant GI and behavioral improvements (Kang DW A. J., 2019). A 2-year follow-up found that these positive changes continued to improve over time (Kang DW A. J., 2019). However, FMT is not FDA approved for ASD at this time, so it may be some time before this therapy is available in the US.

Re-establishing a healthy gut microbiome benefits the gut-brain axis that has become dysfunctional in ASD (Kang DW A. J., 2017). Also, simply removing the pain and distraction of a dysbiotic gut can help children concentrate better and benefit from speech, behavioral and other therapies they may be undergoing (Kang DW A. J., 2017).

In addition to dysbiosis, leaky gut is involved in ASD. A higher percentage of abnormal intestinal permeability, or commonly called leaky gut, was observed in 36.7% of patients with ASD compared with 4.8% of control children (Li Q H. Y., 2017).

In fact, the integrity of both the gut barrier and the BBB were impaired in ASD individuals (Li Q H. Y., 2017). Increased intestinal permeability results in the entry of the toxins and bacterial products into the bloodstream.

These circulating inflammatory molecules are then able to cross the blood-brain barrier, creating inflammation and immune responses in the brain (Li Q H. Y., 2017). For example, lipopolysaccharide (LPS), components of the cell wall of gram-negative bacteria, is increased in the serum of ASD compared with healthy individuals and is associated with impaired social behavior (Li Q H. Y., 2017).

Food sensitivities are often a problem, which ties back to a dysfunctional gut. Over 40% of children with ASD have food sensitivity issues, most commonly to wheat and milk products (Horvath K P. J., 2002).

The breakdown of gluten by pancreatic and intestinal enzymes produces ‘exorphins’ or undigested proteins.  When leaky gut is present, these undigested proteins can then enter into circulation and the central nervous system where they have a morphine-like effect (Reichelt K, 2003).

An increase in proteins, including opiates, has been linked to disruption in social awareness and behavior (Reichelt K, 2003). This sequence of events can occur with casein, from dairy products, as well (Reichelt K, 2003). Finally, gluten and casein increase zonulin, which is a protein that increases gut permeability i.e. leaky gut.

There is also a relationship between gut fungi or yeast and ASD. Yeast in the gut, particularly candida albicans, can result in less carbohydrates and minerals absorption and a higher release of toxins (Li Q H. Y., 2017).

A lower yeast rate of 19.6% was identified in non-autistic healthy volunteers (Li Q H. Y., 2017). It was found that in children with ASD, candida was two times more abundant than in normal individuals and that 81.4% of the yeast strains were candida, especially candida albicans (Li Q H. Y., 2017).

Candida can release ammonia and toxins that can induce autistic behaviors (Li Q H. Y., 2017). The changes in the bacterial microbiota in ASD individuals result in the growth of candida, which worsens the dysbiosis and can induce abnormal behaviors (Li Q H. Y., 2017).

SCFAs also play a critical role in patients with ASD. We talked about SCFAs here. SCFAs are products of the gut bacterial fermentation of carbohydrates and provide benefits to the human body.

Different SCFAs can be imbalanced in the gut of ASD patients. For example, proprionic acid, PPA, is a short-chain fatty acid that is mainly produced by Clostridia, Bacteroidetes, and Desulfovibrio bacteria, which are more frequently found with ASD, and can cross the BBB and induce ASD-like behaviors (Li Q H. Y., 2017). Higher PPA can lead to impaired social behavior, likely by altering some neurotransmitters, such as dopamine and serotonin (Li Q H. Y., 2017).

Finally, the impact of glyphosate on the gut is complex and multi-faceted. We cannot go into the tremendous amount of detail here but Stephanie Seneff has done so in this paper (Samsel A, 2015). There are multiple ways in which glyphosate can contribute to and worsen ASD. We advise avoidance and will explain how you can do that later in this article series on ASD.

Treatments used to date for ASD include behavioral therapy, speech and social therapy, diet / nutrition and medical treatments. However no medical treatment has been approved to treat core symptoms of ASD, such as social communication difficulties and repetitive behaviors (Kang DW, 2019). Considering the link between the gut and brain, the first approach should be to address gut health.

— To Be Continued —

Due to the complexity of ASD, we can’t cover everything that we want to say in one blog post. So please tune in again next week for ASD: Part 3, when we will outline specific action steps related to diet, supplements and lifestyle that you can take to address ASD.

If you want to address ASD sooner, then please get in touch with us today, by booking a free 15 minute discovery call here. We can answer your questions and help you book an initial consult with one of the functional medicine doctors in our clinic.

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