Does Inflammation Play A Role In Autism?

Updated: Sep 19, 2018


April is Autism Awareness Month. In honor of the children and families that are dealing with this issue, we will continue with a series of articles addressing key areas of concern and body systems that could be involved. At a medical meeting in 2013, Dr. Michael Stone stated “once you know one child with autism, you know one child with autism.” [1] This statement is true and very important to understand. Despite having the same diagnosis, no two children will present exactly the same. Also, it is crucial to avoid labels. These children, like all children, are unique and wonderful with their own specific strengths, weaknesses, talents, personalities, etc.


What is Inflammation?

Photo by Samantha Hurley from Burst

In the last article, we covered several key concepts including allostatic load/overload, gastrointestinal dysfunction and nutrient deficiencies and how they intertwine. Let’s continue our discussion now with inflammation. When you hear the word inflammation, what do you think of? Redness. Swelling. Pain. These are all correct and we see these issues with an acute injury like an ankle sprain. These symptoms are a result of the body responding to that injury, i.e. an ankle sprain in this example. We actually want some redness, some swelling and even some pain. The redness and swelling are a part of the healing process and help with repair, turnover and adaptation of the injured tissue. [2] The pain experienced helps us to avoid placing more stress on the injured ankle which allows it to heal.


That is a brief explanation of acute inflammation, but did you know there is also chronic inflammation? Chronic inflammation does not present with the same symptoms. Actually, it often goes unnoticed because the inflammation is low grade and persistent. So it gradually leads to different issues including degeneration of various tissues in the body. [2] There is also evidence that this low grade inflammation is related to cardiometabolic disease and other chronic diseases. [3]


What Does This Have To Do With Autism Spectrum Disorder?

According to Dr. David Perlmutter, a neurologist, in a podcast with Generation Rescue, “Autism is fundamentally an inflammatory disorder and that inflammation is derived from the gut. [4] In the last article, we discussed how many children with Autism Spectrum Disorder (ASD) have also been shown to have increased intestinal permeability, aka leaky gut. [5] This allows for increased circulating lipopolysaccharides, aka endotoxins, which results in an immune response and inflammation. [6] These children also tend to have

Figure 6 from Dr. Fasano’s paper

other gut dysfunction. This can include altered gut microbiota and activation of the mucosal immune response. [7] The gut symptoms experienced by children with ASD is similar to the symptoms reported by people experiencing Irritable Bowel Syndrome (IBS). [7] Several Studies have shown the presence of intestinal inflammation in IBS, specifically low grade mucosal inflammation. [8]


Is The Inflammation Only In The Gut?

This shows a possible pathway for chronic low grade inflammation in anyone who suffers from gastrointestinal dysfunction whether they are young or old or have ASD or not. But is this inflammation isolated to the gut? No, it is not!

image at https://pixabay.com/photo-1845962/

There is a link between the gut and the brain and the gut microbiota and the brain. [9] So, inflammation in the gut can lead to inflammation in the brain/Central Nervous System (CNS). This type of inflammation is known as neuroinflammation. There is current research that is looking into the role of specific neural cells and neuroinflammation in regards to ASD. [10] These specific neural cells are called microglia which are one of the types of neuroglial cells in the CNS. Microglia play a role in the immune system for the CNS. This activity is beneficial for the development of connections, i.e. synapses, between neurons in a developing brain. If these processes and these cells are not functioning properly, it can affect neural development and result in a variety of neurodevelopmental disorders. [11]

Figure 1 from Immune System’s Role in the Biology of Autism [12]

There is speculation now that inflammation and altered immune function can lead to disruptions in the blood brain barrier. These disruptions appear to be mediated by lipopolysaccharides, aka endotoxins. [13] Initially, it was believed that very little could pass through the blood brain barrier and this mechanism was in place as a way to protect the brain. However, it is now known that the peripheral immune response signals are sent to the CNS which shows that there is communication between these two systems. [14] The brain also has many mast cells which are a part of our immune system. These mast cells can be activated by Corticotropin-Releasing Hormone (CRH), which is released in response to stress. CRH can lead to mast cell dependent disruption of the blood brain barrier [15] and increased inflammation. (CRH and stress have been covered here, here and here.)


Now What?

Can anything be done to help decrease this inflammation in the gut and the CNS? Yes! Probiotics can help to decrease inflammation in the gut. Saccharomyces boulardii has been shown to inhibit the production of pro-inflammatory cytokines (small proteins involved in cell signaling) and can help maintain balance of the gut microbiota. [16] Another study found that supplementation with a different strain of probiotic helped to improve many behavioral symptoms associated with ASD. [17] This study was performed in mice but it still shows that probiotics may have wide ranging benefits that extend beyond the gut.

Photo by Sarah Pflug from Burst

Remember from the previous article that we do not want to always use an anti-inflammatory like acetaminophen. Prolonged use of these types of medications can lead to increased intestinal permeability and inflammation of the gut. [18] So taking acetaminophen to deal with chronic low grade inflammation could possibly worsen the issues you are trying to treat.


The Tip of the Iceberg

We have only scratched the surface regarding inflammation and its role in ASD or any other chronic condition. Inflammation is a complex and involved process that when working optimally helps us to restore and heal our body. However, when it is not working optimally, it can lead to a wide array of issues. It is also closely tied to many different body systems like our gastrointestinal tract, CNS and immune system. This is why we must address each individual as an individual and address the entire body. After all, our bodies do not work as distinct separate systems but functions together to accomplish much more that it could if it was simply the sum of each individual part.

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Disclaimer:

This article is for educational use only. Nothing contained in this article should be considered, or used as a substitute for, medical advice, diagnosis or treatment. This article does not constitute the practice of any medical, nursing or other professional health care advice, diagnosis or treatment. Always seek the advice of a physician or other qualified health care provider with any questions regarding personal health or medical conditions. Never disregard, avoid or delay in obtaining medical advice from your doctor or other qualified health care provider because of something you have read in this article. If you have or suspect that you have a medical problem or condition, you should contact a qualified health care professional immediately. If you are in the United States and are experiencing a medical emergency, you should dial 911 or call for emergency medical help on the nearest telephone.


References/Citations:

  1. Dr. Jeffrey S. Bland. (2014). The Disease Delusion: Conquering the Causes of Chronic Illness for a Healthier, Longer and Happier Life. New York: HarperCollins Publishers.

  2. Claudio Franceschi, Judith Campisi; Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases, The Journals of Gerontology: Series A, Volume 69, Issue Suppl_1, 1 June 2014, Pages S4–S9, https://doi.org/10.1093/gerona/glu057

  3. Minihane AM, Vinoy S, Russell WR, et al. Low-grade inflammation, diet composition and health: current research evidence and its translation. The British Journal of Nutrition. 2015;114(7):999–1012. doi:10.1017/S0007114515002093.

  4. http://www.blogtalkradio.com/generationrescue/2015/07/30/chatautism-with-david-perlmutter-md-autism-the-gutbrain-connection

  5. de Magistris, L., Familiari, V., Pascotto, A., Sapone, A., Frolli, A., Iardino, P., Carteni, M., De Rosa, M., Francavilla, R., Riegler, G., Militerni, R., and Bravaccio, C. Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr. 2010 Oct;51(4):418–24. doi: 10.1097/MPG.0b013e3181dcc4a5.

  6. Fasano, A. Zonulin and Its Regulation of Intestinal Barrier Function: The Door to Inflammation, Autoimmunity and Cancer. Physiological Reviews 2011 91:1, 151–175. https://www.physiology.org/doi/full/10.1152/physrev.00003.2008

  7. Crithcfield, J. W.,van Hemert, S., Ash, M., Mulder, L., and Ashwood, P. The Potential Role of Probiotics in the Management of Childhood Autism Spectrum Disorders. Gastroenterology Research and Practice Volume 2011 (2011), Article ID 161358, 8 pages http://dx.doi.org/10.1155/2011/161358

  8. Barbara G, De Giorgio R, Stanghellini V, et al. A role for inflammation in irritable bowel syndrome?. Gut 2002;51:i41-i44.

  9. Li Q, Han Y, Dy ABC, and Hagerman RJ. The Gut Microbiota and Autism Spectrum Disorders. Frontiers in Cellular Neuroscience. 2017;11:120. doi:10.3389/fncel.2017.00120.

  10. Pardo, C. A., Vargas, D. L., and Zimmerman, A. W. Immunity, neuroglia and neuroinflammation in autism. Int Rev Psychiatry. 2005 Dec;17(6):485–95. https://www.ncbi.nlm.nih.gov/pubmed/16401547/

  11. Takano T, Role of Microglia in Autism: Recent Advances. Dev Neurosci 2015;37:195–202. https://www.karger.com/Article/FullText/398791#

  12. Goines P, Van de Water J. The Immune System’s Role in the Biology of Autism. Current opinion in neurology. 2010;23(2):111–117. doi:10.1097/WCO.0b013e3283373514.

  13. Banks, W. A. and Erickson, M. A. The blood-brain barrier and immune function and dysfunction. Neurobiol Dis. 2010 Jan;37(1):26–32. doi: 10.1016/j.nbd.2009.07.031. Epub 2009 Aug 5. https://www.ncbi.nlm.nih.gov/pubmed/19664708?dopt=Abstract

  14. Quan N. Immune-To-Brain Signaling: How Important are the Blood–Brain Barrier-independent Pathways? Molecular neurobiology. 2008;37(2–3):142–152. doi:10.1007/s12035–008–8026-z.

  15. Theoharides, T. C and Zhang. B. Journal of Neuroinflammation 2011, 8:168 https://doi.org/10.1186/1742-2094-8-168

  16. Pothoulakis C. Review article: Anti-inflammatory mechanisms of action of Saccharomyces boulardii. Alimentary pharmacology & therapeutics. 2009;30(8):826–833. doi:10.1111/j.1365–2036.2009.04102.x.

  17. Hsiao, Elaine Y. et al. Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders. Cell , Volume 155 , Issue 7 , 1451–1463. http://www.cell.com/cell/fulltext/S0092-8674(13)01473-6

  18. Sigthorsson G, Tibble J, Hayllar J, et al. Intestinal permeability and inflammation in patients on NSAIDs. Gut 1998;43:506–511.

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