What causes autism? This question has sparked heated debate and intense research in an attempt to unravel the complexities of this condition. But what if the journey to unraveling autism's mysteries led us to an unexpected starting point – the gut?
Today we’re going to explore the intricate and complicated link between autism and a microscopic microbe that resides in our gut – a bacterial species known as Clostridium. Let’s start by defining exactly what autism is.
What Is Autism?
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by a range of challenges related to social interaction, communication, and repetitive behaviors. It is referred to as a “spectrum” because the symptoms and severity can vary widely among individuals. Some common features of ASD include:1
- Difficulties in social interactions
- Challenges in communication (both verbal and nonverbal)
- Repetitive behaviors or restricted interests
- And sensory sensitivities
While autism cannot be traced back to a single root cause, there’s one underlying factor that has an undeniable impact on the development and severity of this complex condition. The underlying factor I’m referring to is what’s known as the gut microbiome.
How Is the Microbiome Related to Autism?
The gut microbiome is the collective community of microbes that inhabit your digestive tract – creating a delicate and intricate ecosystem that’s intertwined with just about every function within your body. And a growing body of research suggests that an unbalanced gut microbiome may play a role in the development and severity of autism. Here's how it works:2,3,4
- Gene mutations and the gut-brain connection: Your gut and brain are tightly connected through the gut-brain axis. This means there is bi-directional communication from gut to brain and brain to gut through the vagus nerve and hormones and neurotransmitters. Certain gene mutations can mess with how your gut and brain communicate – throwing off your gut's balance and disrupting its normal function.
- Changes in gut bacteria in autism: Studies show that individuals with autism often have a distinct shift in their gut bacteria.
- Increase in harmful metabolites: The shift in gut bacteria leads to an overgrowth of “bad” bacteria that produce metabolites. These substances, including false neurotransmitters that may act like neurotoxins, contributing to some of the effects observed in autism.
- Increased gut permeability: People with autism may also have an increase in gut permeability. This means the lining of their gut is compromised, creating “gaps” that allow toxins and bacterial products to leak into the bloodstream. Ultimately, this can impact and impair brain function. Some of the most inflammatory substances are lipopolysaccharides also known as “LPS” which create endotoxemia or toxins leaking into the bloodstream.
These underlying disruptions in the gut create the perfect recipe for altered brain function, also called “neuro atypia” of autism. And recent research is finding that there may be one strain of gut bacteria in particular that can give us even more insight into the underlying imbalances that contribute to ASD – a strain of bacterial species known as Clostridium.
What Is Clostridium?
Clostridium is a genus of bacteria that includes a diverse group of anaerobic, spore-forming bacteria. Many Clostridium species are normal residents of the human gut microbiota, where they contribute to the complex ecosystem of microorganisms that inhabit your digestive tract – playing pivotal roles in fermentation processes and the breakdown of complex carbohydrates. Other pathogenic species of Clostridium can produce toxins and cause diseases, but they are typically kept in check by the beneficial bacteria in your gut.5
So, the presence of Clostridium species is perfectly normal and healthy. But your gut is designed to maintain a fragile and fickle balance. If this delicate harmony is thrown out of whack and strains of Clostridium bacteria begin to over-colonize and overpopulate the gut, it can have distinct impacts on your brain.
And these impacts might just be the key to understanding autism.
How Can Clostridium Impact the Brain In Autism Spectrum Disorder?
An overabundance of clostridium bacteria can impact the brain via two distinct pathways:6
- The inhibition of an enzyme known as dopamine beta-hydroxylase or DBH– resulting in elevated levels of dopamine
- Decreased activation of a pivotal protein known as the Sonic Hedgehog protein
Let’s break these down in the simplest terms possible.
Inhibition Of Dopamine Beta-Hydroxylase (DBH) Results In Elevated Dopamine And Dopamine Metabolites
An overabundance of Clostridium can lead to hazardously high levels of dopamine and dopamine metabolites via a process that goes something like this:6
- Dopamine is released: Dopamine is a neurotransmitter, a chemical messenger that transmits signals in the brain and other areas of the nervous system. It plays a crucial role in various physiological functions, including mood regulation, reward and pleasure, motor control, and the reinforcement of behaviors.
- Dopamine is converted into norepinephrine: Some of the dopamine released in the brain is converted into norepinephrine (noradrenaline) – another important neurotransmitter and hormone – with the help of an enzyme known as dopamine beta-hydroxylase or DBH.
- DBH is inhibited: As Clostridium species break down and metabolize amino acids (the building blocks of protein), they produce two separate compounds known as HPHPA and 4-Cresol. Both of these by-products serve as DBH inhibitors – blocking this enzyme's ability to convert dopamine into norepinephrine.
- Dopamine levels rise: By inhibiting or blocking the enzymatic action of DBH, an increase in HPHPA and 4-Cresol subsequently leads to an increase in levels of dopamine and dopamine metabolites.
- And here’s the rub! Although dopamine is a feel-good chemical, in this case excessive dopamine levels become TOXIC
- Excessive dopamine levels can become toxic to brain cells – inciting damage by:
- Triggering oxidative damage
- Damaging neurons and neuronal mitochondria
- Provoking apoptosis (cellular death) of microglia
- Excessive dopamine levels can become toxic to brain cells – inciting damage by:
Many studies of the urine of children with autism have found elevated levels of HPHPA and 4-Cresol. This is frequently measured in a lab test called urinary organic acids. It’s these excessively elevated levels of dopamine and dopamine metabolites that create a biochemical storm that harms the brian – inciting structural and mitochondrial damage that can autistic symptoms.
Decreased Activation Of the Sonic Hedgehog Protein
In addition to skyrocketing dopamine levels in the brain, Clostridium can elicit even more problematic shifts by decreasing the activation of a critical developmental protein in the brain. The process goes something like this:6
- The Sonic Hedgehog Protein is secreted: Sonic Hedgehog is a crucial protein in brain development – acting as the architect that guides cells, establishes different brain regions, directs nerve cell paths, and contributes to the formation of both the brain and spinal cord. It orchestrates proper connectivity and organization – thus influencing the behavioral outcomes of organisms during embryonic development.
- Production of hydroxyphenylpyruvate acid: As Clostridium bacteria metabolize certain amino acids in your gut, they produce a by-product known as hydroxyphenylpyruvate acid or HPPA as a metabolic byproduct. An over-colonization of Clostridium bacteria can cause HPPA levels to rise high above normal.
- Depletion of Coenzyme A: Elevated levels of HPPA can then deplete a cellular cofactor known as Coenzyme A or CoASH. CoAsh plays a central role in various metabolic processes by facilitating the transfer of acyl groups – thus enabling the breakdown of fats and carbohydrates to be utilized in energy production by your cells.
- Depletion of fatty acids and cholesterol: This depletion of CoAsh can subsequently hinder your ability to properly metabolize fats – thus resulting in the depletion of cholesterol and activated fatty acids (aka fatty acids that your body can actually utilize). Both cholesterol and activated fatty acids are necessary for the proper activation of the Sonic Hedgehog Protein.
- Disruption in brain development: Depleted cholesterol and activated fatty acids equals decreased activation or signaling of the Sonic Hedgehog Protein during brain development. This can lead to various developmental abnormalities – altering the patterning and growth of the central nervous system and the formation of distinct brain regions. This impaired activation of Shh can ultimately result in structural and functional deficits in the developing brain – potentially leading to the underlying changes seen in autism.
Interestingly, researchers have found that specific fatty acid levels directly correlate with the severity of autistic symptoms as based on the Autism Diagnostic Observation Schedule or ADOS – the assessment tool used to diagnose and evaluate autism spectrum disorder. These findings underscore the fact that there is a clear interruption in the ability to activate and utilize fatty acids in the brains of those with autism.
So, where do these findings leave us? And is there anything we can do to address this overabundance of Clostridium?
How Can We Address Clostridium Overgrowth and Dysbiosis In Autism Spectrum Disorder?
Studies have found that modulating the microbiome of individuals with autism spectrum disorders can yield impressive results. Taking steps to create intentional and strategic shifts to the delicate ecosystem within the gut has been found to dramatically reduce the behavioral symptoms seen in autism and drastically improve the quality of life of those living with this diagnosis.
Possible Interventions for Excess Clostridia
- Metronidazole
- Tinidazole
- Vancomycin
- Fidoxomicin
- Fecal microbiota transplant (FMT)
- Black Cumin Seed
If you or a loved one is grappling with the effects of autism and looking to address any gut imbalances, I cannot overemphasize the importance of partnering with an experienced Integrative and Functional Medicine Doctor. They can help you create a comprehensive plan to help address a plethora of factors that may help improve symptoms. If you do work with a Functional Medicine Practitioner, they may suggest a protocol that encompasses some or all of the following treatment options:
- Antimicrobial medications: A round of antimicrobials may be helpful to get bacterial overgrowth under control and get their populations back in check. This may include the medication Vancomycin daily for 7-10 days then pulsed every 3 days. Vancomycin is also sometimes used in conjunction with another antimicrobial – either Metronidazole or the new drug Dificid – given as a course and then pulsed every 3 days for 30 days.
- Black cumin seed oil: Black cumin seed oil is a potent antimicrobial, antioxidant, and anti-inflammatory agent – making it an excellent tool for addressing an imbalance in the gut microbiome.
- Supplementation with coenzyme A or its precursors: Adding in external coenzyme A or the precursors that allow your body to synthesize more of this enzyme, can help re-establish the pathway that allows the body to properly break down, activate, and utilize fatty acids. Pantothenic acid – also known as vitamin B5 – is the primary precursor needed to support coenzyme A production.
- Following a gut-friendly diet: Prioritizing fresh whole foods and minimizing refined oils and sugars, artificial sweeteners, and processed foods (which are irritating and inflammatory to the gut) is key to creating a balanced gut. It can also be helpful to add in supplements like Gut Shield or Collagen to bolster the integrity of the gut lining.
- Incorporating probiotics: Addressing Clostridium overgrowth is only a piece of the puzzle when it comes to restoring equilibrium to the delicate ecosystem within your gut. It can be helpful to add in daily probiotics to help repopulate the gut with beneficial strains of bacteria. Click here to learn more about the link between the microbiome and autism.
- Addressing toxins and mold exposure: Exposure to toxins – especially the mycotoxins found in mold – can have a major impact on both gut health and autism symptoms. Click here to read more about the link between autism and mold.
These steps can have a monumental impact when it comes to establishing a diverse and thriving microbiome that can help quell the biochemical storm contributing to the underlying changes seen in autism.
One Step Closer To Understanding Autism Spectrum Disorder
While we may not be able to cure or entirely prevent autism spectrum disorders, healing and optimizing the gut microbiome may just be the secret to better understanding and addressing this complex condition. Knowing this gives us insight into how we can best support and enhance the lives of those with autism and their families.
So if you have autism spectrum disorder or are a caregiver to someone with autism, please know that you are not simply at the mercy of a diagnosis. You have an immense amount of power through the day-to-day choices you make.
I’m passionate about empowering you – my patients and readers – with the knowledge and resources you need to channel that power into healing and creating the healthiest, happiest, very best version of you as possible. So, to help you access the exact tools and information you need, I’ve created a Resource Roadmap – and it’s yours for free.
It’ll help you zero in on the information that’s most useful for you and help you stay in the driver's seat when it comes to your health. Click here to download your Resource Roadmap today!
Resources:
- What is Autism Spectrum Disorder? | CDC
- Research confirms gut-brain connection in autism | ScienceDaily
- Association Between Gut Microbiota and Autism Spectrum Disorder: A Systematic Review and Meta-Analysis – PMC (nih.gov)
- Frontiers | Autism Spectrum Disorder Associated With Gut Microbiota at Immune, Metabolomic, and Neuroactive Level (frontiersin.org)
- Clostridium – an overview | ScienceDirect Topics
- IMCJ May 2023 (imjournal.com)
* These statements have not been evaluated by the Food and Drug Administration. The product mentioned in this article are not intended to diagnose, treat, cure, or prevent any disease. The information in this article is not intended to replace any recommendations or relationship with your physician. Please review references sited at end of article for scientific support of any claims made.
1 Comment
“Many studies of the urine of children with autism have found elevated levels of HPHPA and 4-Cresol. This is frequently measured in a lab test called urinary organic acids. It’s these excessively elevated levels of dopamine and dopamine metabolites that create a biochemical storm that harms the BRIAN – inciting structural and mitochondrial damage that can autistic symptoms.””
We certainly don’t want to harm Brian… 🙂
Yes. I *do* carefully read medical articles. This one has an intriguing premise, and there should be some animal studies to check the hypothesis. I believe that I have been struggling with high-functioning Asperger’s or Autism most of my life. Most of the time, it is not too bad. :-/
Thank you very much for your diligent research and benefiting many souls.
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