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The Hazards of Gluten Sensitivity – Can Grains Affect the Brain?

Gluten Sensitivity is a term that is being heard more and more. However, what exactly does it mean? And what are the implications of being sensitive to gluten?

Celiac disease is the most commonly recognized condition associated with gluten. It is an autoimmune condition whereby gluten provokes an abnormal immune response, resulting in the body attacking and damaging the lining of the small intestine. This leads to the common digestive symptoms experienced. In addition to this, nutritional deficiencies, poor growth, weight loss and some neurological signs may also be seen.

Gluten Sensitivity Different to Celiac Disease

Gluten Sensitivity may involve different mechanisms to those involved in celiac disease and may often present with more psychological or neurological symptoms. In fact, gluten sensitivity has been shown to be a common factor, in both children and adults, with conditions such as ADHD1, ASD1, seizures2, depression3, anxiety disorders4 and schizophrenia5. Gluten ataxia, an issue involving problems with co-ordination, speech and balance, is a neurological condition involving a reaction to gluten and is becoming more recognized6.

Gluten sensitivity, sometimes referred to as Non-Celiac Gluten Sensitivity (NCGS), has been shown to be 6 times more prevalent than celiac disease 7. Some may ask why the incidence of gluten sensitivity seems to be on the rise? This apparent rise in cases may be down to several factors including an increased awareness of the impact of gluten, grains containing higher gluten content or an increase in the consumption of gluten-containing grains or products. Whatever the reason for the rise in cases, the evidence is mounting on the impact of gluten on the brain.

How Does Gluten Cause a Problem?

Gluten-containing grains such as wheat, rye, barley and spelt contain toxic protein fractions in the form of gliadins, glutenins and other prolamins. These toxic protein fractions have been shown to have wide-ranging effects on the body and may disrupt normal gut balance8 and involve the immune system in susceptible people9. Although it is commonly the protein fractions that cause a reaction in sensitive individuals, it is possible to react to other components within gluten.

During digestion of gluten compounds such as gluteomorphins, also called gliadorphins, are released. These have an opioid-like effect on the brain and have been linked to conditions such as ASD10.

Immune Involvement

The immune reaction to gluten may be complex and may, or may not, involve specific antibodies.In celiac disease there may be several antibodies present including anti-endomysial antibodies (EMA), anti-tissue transglutaminase antibodies (tTG),) or IgE mediated antibodies. In gluten sensitivity, these antibodies may be absent and there is evidence to show an increase in anti-gliadin antibodies11. Antibodies to deamidated gliadin peptides can also be raised and testing for their presence may be particularly useful in young children12. It is thought that anti-gliadin antibodies could negatively affect a protein involved in neurotransmitter release, thereby directly interfering with neurotransmitters and potentially affecting psychological function13. Gliadin itself may activate the production of chemical messengers called cytokines, which are involved in the inflammatory response, setting the stage for an increased inflammatory response14. Links have been made to increased cytokine levels and the development of conditions like ADHD and ASD15.

Gut Lining

One interesting finding by researchers is that the gut lining of those with gluten sensitivity may be distinctly different to those with celiac disease. There does not always seem to be flattening of the villi on the gut lining and it is possible to have normal intestinal permeability16 and a healthy gut lining17 in cases of gluten sensitivity. Having said that, there is a high incidence of leaky gut in association with ASD and ADHD18.

Microbiome Disruption

The microbiome is known to contribute to overall gut health and play a role in immune system functioning. Their link to good health is undisputed and a direct link between the gut and brain has been established. The microbiota can send signals to the brain via several mechanisms including activation of the vagal nerve and through hormones19.  An imbalance in the microbiome has been linked to several psychological issues including depression and anxiety20.

Both gluten and gliadin have been shown to disrupt the microbiome in susceptible individuals21. There is evidence to show that the use of probiotics, to restore balance in cases of dysbiosis, in ADHD and ASD gives improvements in symptoms22.

Risk factors – Why are Some People More Susceptible?

Genetics – The link between celiac disease and inherited DNA variations is well known and almost all celiacs have HLA-DQ2 and HLA-DQ8 haplotypes (A haplotype is a group of genes inherited together from a single parent). The incidence of these haplotypes in association with gluten sensitivity does exist but varies from 50%23-25 to 90%26

Microbiome transfer – Children are born with a sterile gut and are reliant upon maternal transfer of microbiota, through vaginal delivery and breast-feeding, to enable them to develop a healthy microbiome. Microbiota play a vital role in brain development and function and microbiome disruption at an early age may have long term consequences including increased susceptibility to gluten sensitivity.

Toxic load – The accumulation of toxins within the body has been linked to hypersensitivity and impaired tolerance of the immune system. One or more triggers, such as gluten, seem to provoke a reaction in those with a high toxic load27.  Inherited toxic load whilst in the womb may also be a factor in children who have developed gluten sensitivity.

 

Key points:

  • Gluten sensitivity is complex and can present with different signs to celiac disease
  • Gluten sensitivity has been shown to be a common factor in ADHD, ASD, depression, anxiety and ataxia
  • Protein fractions in gluten may disrupt normal gut balance and involve the immune system
  • Morphine like compounds released during digestion of gluten have opioid-like effects on the brain
  • Gut lining health and microbiota balance may play a key role in sensitivity to gluten
  • There is a genetic link to gluten sensitivity
  • The high toxic load may impact on immune tolerance to gluten

Gluten-free

Gluten poses risks for some children and adults and can have a large impact on brain functioning. It is clear that many people with gluten sensitivity get relief from many of their symptoms on a gluten-free diet. For some the benefits are within a few days or weeks, for others, it takes longer. It is also worth considering a probiotic supplement in order to restore any imbalances. If you are considering a gluten-free diet or a probiotic it is always best to work with a well-trained and experienced functional health practitioner.

Overview

Gluten can be a hazard and have a large impact on brain functioning. Avoiding gluten-containing foods can dramatically reduce both psychological and neurological symptoms.

References

  1. Niederhofer H, Pittschieler K. (2006) A preliminary investigation of ADHD symptoms in persons with celiac disease. Journal of Attention Disorders. 10:200–204.
  2. Peltola M, Kaukinen K, Dastidar P, Haimila K, Partanen J, Haapala AM, et al. (2009) Hippocampal sclerosis in refractory temporal lobe epilepsy is associated with gluten sensitivity. Journal of Neurology, Neu-rosurgery and Psychiatry. 80:626–630.
  3. Ruuskanen A, Kaukinen K, Collin P, Huhtala H, Valve R, Maki M, et al. (2010) Positive serum antigliadin antibodies without celiac disease in the elderly population: Does it matter? Scandinavian Journal of Gastroenterology. 45:1197–1202.
  4. Jackson, J. R., Eaton, W. W., Cascella, N. G., Fasano, A., & Kelly, D. L. (2012). Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity. Psychiatric Quarterly, 83(1), 91-102.
  5. Dickerson F, Stallings C, Origoni A, Vaughan C, Khushalani S, Leister F, et al. (2010) Markers of gluten sensitivity and celiac disease in recent-onset psychosis and multi-episode schizophrenia. Biological Psychiatry. 68:100–104.
  6. Hadjivassiliou M, Boscolo S, Davies-Jones GA, Grunewald RA, Not T, Sanders DS, et al.(2002) The humoral response in the pathogenesis of gluten ataxia. Neurology.  58:1221–1226.
  7. Hadjivassiliou M, Grunewald RA, Davies-Jones GA. (2002) Gluten sensitivity as a neurological illness. Journal of Neurology, Neurosurgery and Psychiatry. 72:560–563.
  8. Hollon J., et al. (2015) Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non- Celiac Gluten Sensitivity. Nutrients 7.3 1565-76.
  9. Palova-Jelinkova L, Rozkova D, Pecharova B, Bartova J, Sediva A, Tlaskalova-Hogenova H, et al. (2005) Gliadin fragments induce phenotypic and functional maturation of human dendritic cells. Journal of Immunology. 175:7038–7045
  10. Cooper, E. L. (2003). Neuroimmunology of autism: a multifaceted hypothesis. International journal of immunopathology and pharmacology, 16(3), 289-292.
  11. Hadjivassiliou M, Williamson CA, Woodroofe (2004) N. The immunology of gluten sensitivity: Beyond the gut. Trends in Immunology. 25:578–582.
  12. Amarri, S., Alvisi, P., De Giorgio, R., Gelli, M. C., Cicola, R., Tovoli, F., … & Volta, U. (2013). Antibodies to deamidated gliadin peptides: an accurate predictor of coeliac disease in infancy. Journal of clinical immunology, 33(5), 1027-1030.
  13. Jackson, J. R., Eaton, W. W., Cascella, N. G., Fasano, A., & Kelly, D. L. (2012). Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity. Psychiatric Quarterly, 83(1), 91-102.
  14. Palova-Jelinkova L, Rozkova D, Pecharova B, Bartova J, Sediva A, Tlaskalova-Hogenova H, et al. (2005) Gliadin fragments induce phenotypic and functional maturation of human dendritic cells. Journal of Immunology. 175:7038–7045
  15. Zubareva, O. E., & Klimenko, V. M. (2013). Increases in Proinflammatory Cytokine Levels at Early Ages as a Risk Factor for the Development of Nervous and Mental Pathology. Neuroscience and Behavioral Physiology, 43(4), 535-541.
  16. Sapone A, Lammers KM, Mazzarella G, Mikhailenko I, Carteni M, Casolaro V, et al. (2010) Differential mucosal IL-17 expression in two gliadin-induced disorders: Gluten sensitivity and the autoimmune enteropathy celiac disease. International Archives of Allergy and Immunology. 152:75–80.
  17. Marsh, M. N. (1992). Gluten, major histocompatibility complex, and the small intestine: a molecular and immunobiologic approach to the spectrum of gluten sensitivity (‘celiac sprue’). Gastroenterology, 102(1), 330-354
  18. de Magistris, L., Familiari, V., Pascotto, A., Sapone, A., Frolli, A., Iardino, P., … & Militerni, R. (2010). Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. Journal of pediatric gastroenterology and nutrition, 51(4), 418-424.
  19. Forsythe, P., & Kunze, W. A. (2013). Voices from within: gut microbes and the CNS. Cellular and molecular life sciences, 70(1), 55-69.
  20. Foster, J. A., & Neufeld, K. A. M. (2013). Gut–brain axis: how the microbiome influences anxiety and depression. Trends in neurosciences, 36(5), 305-312.
  21. Hollon J., et al. (2015) Effect of Gliadin on Permeability of Intestinal Biopsy Explants from Celiac Disease Patients and Patients with Non- Celiac Gluten Sensitivity. Nutrients 7.3: 1565-76. 
  22. Critchfield JW, van Hemert S, Ash M, Mulder L, Ashwood P. (2011) The potential role of probiotics in The management of childhood autism spectrum disorders. Gastroenterology research and practice. 161358.
  23. Bizzaro, N., Tozzoli, R., Villalta, D., Fabris, M., & Tonutti, E. (2012). Cutting-edge issues in celiac disease and in gluten intolerance. Clinical reviews in allergy & immunology, 42(3), 279-287.
  24. Monsuur AJ, Wijmenga C (2006) Understanding the molecular basis of celiac disease: what genetic studies reveal. Ann Med  38:578-591.
  25. Mazzarella G, Maglio M, Paparo F, Nardone G, Stefanile R, Greco L, van de Wal Y, Kooy Y, Koning F, Auricchio S, Troncone R: (2003) An immunodominant DQ8 restricted gliadinpeptide activates small intestinal immune response in in vitro cultured mucosa from HLA-DQ8 positive but not HLA-DQ8 negative coeliac patients. Gut  52:57-62.
  26. Hadjivassiliou M, Grunewald RA, Chattopadhyay AK, Davies-Jones GA, Gibson A, Jarratt JA, et al. (1998) Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia. Lancet. 352:1582–1585.
  27. S. J. Genuis, (2010) Sensitivity-related illness: the escalating pandemic of allergy, food intolerance and chemical sensitivity.  Science of the Total Environment, vol. 408, no. 24, pp. 6047–6061

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