By Gita Gupta

In this post, I summarize a study from a group of well-known researchers which reveals new insights on gastrointestinal (GI) issues in autism. The study showed that the GI tract of children with autism has significant differences in mitochondrial function, compared to neurotypical children with similar GI issues.

As parents like us are well aware, the list of gastrointestinal issues in children with autism is a long one – it includes inflammation, gut dysbiosis, chronic diarrhea, constipation, gastroesophageal reflux disease (GERD), gut motility issues, deficiencies in enzymes important for digestion. Not so long ago, it was common to assume that GI issues like these were “behavioral” rather than rooted in physiology.  Newer research, like this study, looks at the underlying biology to find answers.

The study looked at mitochondrial function in the GI tract in children with autism and compared it to neurotypical children with non-specific GI issues, as well as neurotypical children with Crohn’s disease. Specifically, the study looked at biopsies from the cecum and rectum. The figure on the right shows where the cecum and rectum are in the large intestine (colon), just to help you to visualize – they are roughly towards the beginning and end of the large intestine.

KEY FINDINGS

1)      THE GI TRACT OF KIDS WITH AUTISM HAS DIFFERENCES IN MITOCHONDRIAL FUNCTION.

Compared to groups of neurotypical children with similar gastrointestinal symptoms, the study found that children with autism had big differences in mitochondrial function.

The main function of mitochondria is to produce energy to power things that go on in the cell. The “factories” that produce energy in the cell are made up of proteins called complexes and there are five of these –  Complex I, II, III, IV and V. This series of complexes is called the Electron Transport Chain (ETC).  The differences in mitochondrial function found in Autism Spectrum Disorder (ASD) kids wasn’t just isolated to any one complex in the ETC; they were found in several ETC complexes.  The study found that multiple ETC complexes were overactive. It’s as if the mitochondria were working harder to deal with stress.

2)      IT’S PROBABLY NOT GENETIC!

In genetic mitochondrial disease, you usually see a defect in one component of the “energy factory” or Electron Transport Chain. In this case, the differences were seen in multiple complexes. So, this probably isn’t genetic – it’s more likely to be an “adaptive response” to factors in the environment. Specifically, the study found that the activity of Complex I was higher in both the cecum and rectum in children with autism. This implies that the difference in Complex I activity may be an abnormality that is more specific to ASD.

3)      GUT BACTERIA PROBABLY PLAYED A ROLE.

The increase in mitochondrial activity was mainly seen in the part of the large intestine called the cecum. This is an area where you’d typically see the by-products of fermentation by gut bacteria. These fermentation by-products include propionic acid and butyrate. These products are called “short chain fatty acids” or SCFA, for short. These SCFAs usually have important functions in the body. However, in children with autism and gut dysbiosis, they are not always a good thing.

Remember the role of clostridia and propionic acid in ASD? Here’s an example you may already be familiar with. I’m sure you’ve heard that bacteria belonging to Clostridia species are abundant in many kids with autism – especially ASD kids who regressed or kids who had GI symptoms before ASD symptoms were seen. These bacteria produce the SCFA propionic acid, which has major effects on mitochondrial function. Propionic acid has been implicated in ASD behaviors in mouse models and also in abnormalities in metabolism in ASD children. (Some of you may already know these negative effects from experience with clostridia species in your own kids.)

Clostridia also make butyrate. Now, these same Clostridia species also make the SCFA butyrate as a major fermentation product.  Butyrate is usually a good thing – it has a lot of positive effects in the intestine. It influences the behavior of neurotransmitters in a positive way; in a mouse model of autism, butyrate was found to improve ASD type behavior. It helps with energy deficits in the colon, reduces inflammation, reinforces the gut barrier and helps with intestinal motility. Outside the colon, it has a number of beneficial effects on metabolism.

On the other hand, when a child has gut dysbiosis, butyrate may not always be a good thing. This study suggests that increased levels of butyrate produced as a result of gut dysbiosis can make the mitochondria overactive.  Animal models show that butyrate can also have the same effects as propionic acid on changes in metabolism and aberrant behavior. In fact, the findings of this study suggest that butyrate might have an even larger role than propionic acid in ASD symptoms. Let’s take a look at how that works.

Cells in the colon are directly dependent on butyrate for fuel. If there was an increase in butyrate for any reason, that would cause an increase in Complex I in colon cells, compared to Complex II. This fits what the researchers found in the colon tissue of ASD kids –   there was an increase in Complex I activity, without a corresponding increase in Complex II activity. This suggests that there is indeed an increase in butyrate in kids with ASD, compared to controls, and it’s making the mitochondria in the GI tract overactive.

Overactive mitochondria can cause behaviors and GI symptoms we see in ASD. When mitochondria become overactive, they become very sensitive to anything that creates oxidative stress. An example of things that create oxidative stress in the GI tract is toxins like synthetic food additives. Add toxins to overactive mitochondria, and you get … you guessed it, mitochondrial dysfunction in the GI tract.

Implications of mitochondrial dysfunction in the colon

• Mitochondrial dysfunction in the GI tract may account for GI symptoms like poor bowel motility and constipation.
• This might also explain why children with ASD who don’t have classic allergies are sensitive to food additives and other toxins, and why they might benefit from organic food or some elimination diets.
• Overactive mitochondria are linked to ASD symptoms like repetitive and stereotypical behaviors.

Putting it all together, I don’t think it’s a coincidence that you often see more of these behaviors in ASD kids when they have GI issues.

YOUR TAKE AWAYS

• There are abnormalities in mitochondrial activity in the lower GI tract of children with ASD which may account for GI symptoms like constipation. If your child has constipation, consider gut dysbiosis and mitochondrial dysfunction as causes.
• Also consider these as causes if your child’s behavior gets worse, because abnormalities in mitochondrial dysfunction may also contribute to repetitive and stereotypical behaviors.
• SCFAs like propionic acid and butyrate are usually positive but can turn into a negative in ASD kids with gut dysbiosis, depending on a number of factors e.g. relative production from various bacterial populations. If you see a deterioration in behaviors, take a look at changes in dietary intake. Especially keep this in mind if you’re supplementing pre-biotics like inulin-type fructans or arabinoxylan-oligosaccharides and see a deterioration in behaviors.
• TACA has reference articles on mitochondrial and gastrointestinal references for parents immediate use (1)

WHAT’S NEXT FOR RESEARCH?

As we learn more about the reasons for changes in SCFA production, and are better able to measure SCFAs in blood, urine and stool, we may be able to find ways to use SCFAs for healing the GI tract, while steering clear of harmful levels.

We greatly appreciate the authors and this research. Studies like this one will help families identify treatable issues for their child living with autism that can positively affect their lives.

For more information about blog author Gita Gupta – please see https://www.tacanow.org/about-taca/ambassadors/

References:

For additional information about mitochondrial function, testing and treatment please see:

https://www.tacanow.org/family-resources/autism-and-mitochondrial-function/

For additional information about gastrointestinal testing and treatment please see:

https://www.tacanow.org/family-resources/the-poop-page/

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