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Objection to the role of gluten in brain dysfunction like autism, ADHD
Frequently cited objection to the role of gluten in neurobehavioral disorders is the fact that there is no positive evidence on conventional tests. However, absence of proof does not mean necessarily there is no proof; it just may be that we do not have tests sophisticated enough.
Is It Leaky Gut or Leaky Gut Syndrome?
Non-celiac gluten sensitivity is a gluten related disease with negative tests
One prime example is of the millions of patients who have been complaining of improved bowel function upon exclusion of gluten despite testing negative for celiac disease. We as gastroenterologists used to routinely think that they are just following a fad and that the perceived
effects were anecdotal and placebo.
In recent years we have found that there is a condition now termed as nonceliac gluten sensitivity (NCGS). Unlike celiac disease, there may be little or no immune reaction. Drs. Verdu and colleagues from the McMaster University, Hamilton, Ontario, Canada call it “No-man’s land between celiac disease and irritable bowel syndrome”. The latter creates a fertile crescent for more research in this field.
Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health
Obviously the public at large was far ahead of medical community in this regard. Even though routine laboratory, imaging and biopsy tests are negative in such patients, evidence from randomized controlled trials has convincingly shown that gluten exclusion indeed helps certain groups of patients with bowel symptoms like irritable bowel syndrome.
Of note: Exclusion of wheat and resolution of bowel symptoms may not always be related to gluten sensitivity, rather due to a fructans present in wheat causing IBS like symptoms based on FODMAPS concept.
Applying gluten relationship argument of NCGS to brain dysfunction
The same or similar arguments of routine tests being negative but patients getting benefit from gluten exclusion as in NCGS could be made for neuro-behavioral disorders like autism, ADHD, schizophrenia as well.
Is It Leaky Gut or Leaky Gut Syndrome?
Opiod hypothesis as mechanism of action of gluten in brain dysfunction
The gluten proteins undergo partial digestion in the intestines resulting in a variety of small complexes of aminoacids or peptides. Some of these peptides are not amenable to further breakdown and their presence results in an immune reaction classically manifesting as celiac disease and its myriad gastrointestinal and non-GI manifestations including skin disorders and cancer.
Some of these peptides are akin to opiod or morphine like neurochemicals (endorphins) found in brain. These externally dervived bioactive compounds also called as exorphins may get absorbed across the gut in certain individuals predisposed due to the genetic background and overlying environmental toxic influences and gain access to the body and ultimately to the brain. In brain, they interact with opiod receptors thus disrupting the finely tuned healthy neurochemical-electrical balance leading to neurological dysfunction.
Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health
Is there evidence that gluten related peptides have opiod-like activity
The data is mainly based on laboratory tests for opiod (morphine) like activity including:
- Actions of these gluten-related peptides can be blocked by opiod/narcotic blocker nalaoxone.
- These peptides displace opiod agonists from parts of brain in animals.
- They stimulate hormonal secretion in the pituitary gland in the brain.
- Because of these actions, these peptides have been termed exorphins in contrast to the normally occurring endogenous opiod-like molecules known as endorphins.
Gluten and autism
- Opiod excess hypothesis championed by experts like Drs. Shattock and Whiteley from the Research Unit, School of Sciences (Health), University of Sunderland, Sunderland, SR2 7EE, UK
- Clinical studies have documented benefit
- Opiod peptides have been documented in urine of patients with autism
- Increased antigliadin antibodies in some neurobehavioral disorders
Is It Leaky Gut or Leaky Gut Syndrome?
Potential mechanism of action in autism
- Deficiency of certain protein digestive enzymes (peptidases)
- Dietary overload of exorphin precursors as a result of increased absorption through the gut.
- Genetically determined kinship of opiod receptors to the gluten-related exorphins in particular areas of brain. This may permit dysfunction notwithstanding low levels of the exorphin in brain. Similar mechanism has been proposed for other disorders like schizophrenia.
- The variation in clinical symptoms depends on the differences in amount of exorphins and strength of attraction for different parts of brain areas with different functions.
How do some autistic subjects show some exceptional talent traits
Exorphins interaction with opiod receptors in brain may not just result in causing dysfuntion but the interaction in certain unique areas may enhance certain talents. For example, studies by Dr. Yoshikawa and colleagues from Kyoto University in Japan show that certain gluten peptides (gluten exorphin 5A and rubiscolin 6 ) selectively bind to delta opiod receptor and when given to mice improves learning performance. This may explain at least in part excellence in certain talents seen among some patients with autism.
Another mechanism: Leaky gut may be involved
One of the mechanisms invoked in gluten related disorders is leaky gut or increased intestinal permeability. The leaky gut allows for these relatively large peptide molecules access to the body and even the brain. Evidence to support leaky gut in non-celiac gluten sensitivity is sketchy at best using the current experimental techniques.
Is It Leaky Gut or Leaky Gut Syndrome?
Wall Street Journal Best Seller Dr. M's Seven-X Plan for Digestive Health
