When it comes to autism spectrum disorder (ASD), diagnosis is a complex process in which the necessary evaluations can take days or even weeks and depend heavily on the expertise of the clinician. This time-consuming and subjective process is driven by an absence of simple diagnostic testing; the physical, psychological, and behavioral symptoms experienced by patients with autism span a broad spectrum and thus far researchers have been unable to identify a single peripheral marker that can be used to achieve diagnostic clarity. However, in recent years, research related to autism and peripheral markers has expanded beyond the search for a single diagnostic test. Instead, researchers have begun using peripheral markers to explore autism-related comorbidities and specific symptom manifestations in patients with the disorder. Of particular interest is a recently-developed blood-based peripheral marker that can be used to identify autism-associated ileocolitis. In the future, clinicians and patients may be able to use information from a test for this peripheral marker to develop an effective, patient-specific strategy for the management of gastrointestinal symptoms in patients with autism.
The Association between Autism and Gastrointestinal Symptoms
The association between autism and gastrointestinal symptoms is well-documented: studies show that children with autism are significantly more likely to experience symptoms such as constipation, diarrhea, pain during defecation, abdominal pain, bloating, and food intolerance or sensitivity. In many cases, these symptoms arise from well-known inflammatory bowel diseases; according to one estimate, children with autism are between 1.3 and 2.4 times more likely to be diagnosed with co-occurring Crohn’s disease or ulcerative colitis than their normally-developing counterparts. However, it is important to recognize that a significant proportion of the patient population suffers from a unique inflammatory bowel disease variant that only occurs in patients who have autism: autism-associated ileocolitis.
Ileocolitis is a type of inflammatory bowel disease that affects the ileum (the back end of the small intestine) and the colon (the front end of the large intestine). Like other inflammatory bowel conditions, it can cause significant gastrointestinal symptoms, such as chronic diarrhea, abdominal cramping, weight loss/trouble gaining weight, and chronic fatigue. Although there is no cure, identifying this condition is important because it can help patients and clinicians develop an effective treatment strategy to manage and minimize ongoing symptoms.
A Peripheral Marker for Autism-Associated Ileocolitis
In 2016, a group of researchers from Wake Forest University in Winston-Salem, North Carolina, published a study characterizing a blood-based peripheral marker for autism-associated ileocolitis in Nature Scientific Reports. Prior to this study, the researchers had successfully used histological analysis—that is, a careful assessment of the patient’s gastrointestinal tissues—to distinguish between the gastrointestinal tissues of patients with autism-associated ileocolitis and tissues from patients with another inflammatory bowel disease, such as Crohn’s disease or ulcerative colitis, as well as from patients who displayed gastrointestinal symptoms that were not associated with inflammation. In their initial work, which was published in the journal PLoS One in 2013, the researchers were able to develop a molecular profile of autism-associated ileocolitis, down to the level of gene expression, which offered both researchers and clinicians exciting opportunities to explore possible treatment options that could be uniquely effective for patients with ileocolitis-associated autism.
At the same time, the researchers recognized that their original method for distinguishing autism-associated ileocolitis from other inflammatory bowel conditions was not feasible for widespread use in clinical settings. Their work had relied on diagnostic endoscopy to obtain gastrointestinal biopsy tissue from children with autism, but this is a difficult, expensive, and highly invasive procedure. Therefore, the researchers set out to develop a peripheral biomarker that could effectively distinguish between autism-associated ileocolitis and gastrointestinal conditions
In order to accomplish this goal, the researchers collected samples from 21 children who had been diagnosed with autism, experienced chronic gastrointestinal symptoms, and had histologic inflammation of the ileum and/or colon. For the control, they obtained samples from 24 children without ASD who experienced gastrointestinal symptoms but did not have histologic inflammation of the ileum or colon. Then, they used the method of principal component analysis (PCA) to compare the whole genome expression profiles of both groups of patients. Ultimately, they were able to find 59 gene transcripts that were expressed differently in the patients with autism-associated ileocolitis. Of these, 9 were expressed in the peripheral blood of patients with autism, making it possible to diagnose autism-associated ileocolitis with a simple blood test for these transcripts.
Exploring Effective Treatment Methods for Patients with Autism-Associated Ileocolitis
In terms of treatment, the implications of the distinction between autism-associated ileocolitis and other inflammatory bowel conditions are not fully clear. However, the determination that the GI symptoms of a patient with autism stem from ileocolitis can help clinicians and patients develop an effective treatment method. Armed with the knowledge that inflammation is the underlying culprit, clinicians may recommend treatments that specifically target inflammatory pathways. There are a variety of diets, such as the Autoimmune Protocol Diet, designed specifically to reduce inflammation in the gut. For patients who want to avoid restrictive diets, inflammation-fighting nutritional supplements offer an appealing alternative. For instance, curcumin is known to be an effective anti-inflammatory when taken in bioavailable forms. Butyric acid may also fight inflammation through several mechanisms: not only do studies suggest that it can directly modulate inflammation pathways in the GI tract, but it may also increase levels of glutathione (GSH), a powerful antioxidant that can prevent free radicals from causing damage that exacerbates gut inflammation.
Peripheral markers for autism-related conditions can be extremely valuable for patients and clinicians who are looking to identify an effective approach for management of a complex combination of symptoms. As new peripheral markers are identified, simple tests may make it much easier to develop effective treatment strategies in the future. For clinicians, parents, and patients who want to explore whether supplementation can help control autism-related ileocolitis, there are already a number of supplements on the market designed with the unique needs of individuals with ASD in mind.
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Walker SJ, Beavers DP, Fortunato J, Krigsman A. 2016. A putative blood-based biomarker for Autism Spectrum Disorder-associated ileocolitis. Nature Scientific Reports. https://www.nature.com/articles/srep35820