While gastrointestinal (GI) complaints are common among children in general, the prevalence of these issues is reportedly1 more than 4-fold higher among children with autism spectrum disorders (ASD). The most frequently observed GI problems in ASD include diarrhea, constipation, and abdominal pain, according to a meta-analysis of 15 studies.2
Research has shown that GI symptoms are associated with a range of potentially interactive effects in ASD, such as sleep disturbance and exacerbation of psychiatric and behavioral symptoms.3 In a 2016 study of children with ASD, those with GI symptoms demonstrated higher rates of anxiety, somatic complaints, and behavioral problems compared with those without GI symptoms.4
Other results point to a link between GI issues and the severity of core ASD symptoms. For example, a study published in 2021 in Autism found that the severity of GI symptoms was associated with the frequency of repetitive behaviors in a sample of 176 children (80% male) aged 2 to 7 years with ASD.5
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In a qualitative study6 published in 2021, Holingue et al interviewed 12 parents with ASD and noted that GI “issues impacted the child’s well-being and the ability to participate in and fully engage in activities” as well as the family’s well-being, and “parents often experienced challenges with seeking accessible and quality health care for their child’s [GI] problems.”
Taken together, these findings reinforce the need for improved understanding and management of GI disorders in this population.While the same treatment strategies are indicated for children with ASD and other patient groups, those with ASD may require an interdisciplinary team to address their various complex and interrelated medical needs.1
Preliminary evidence suggests that resolution of GI symptoms through approaches such as probiotic supplementation and fecal microbiota transplant is associated with behavioral improvements in children with ASD.1 However, prospective studies are warranted to further elucidate these observations.
To gain further insights regarding the connection between GI disorders and ASD, we interviewed Deborah Goldman, MD, a pediatric gastroenterologist at Cleveland Clinic Children’s in Ohio, and Kara Gross Margolis, MD, associate director for clinical and translational research and director for brain gut research at the NYU Pain Research Center in New York and coauthor of a 2020 review and other papers relevant to the topic.1,7
What are the mechanisms underlying GI symptoms in ASD?
Dr Goldman: ASD is a neurodevelopmental disorder of unknown etiology, characterized by presentation in the first few years of life with impairment in social interaction and communication with specific criteria established to support the diagnosis. The incidence of ASD has been reportedly increasing over the past several decades.
GI symptoms are commonly described features associated with ASD, with various theories of causality which have yet to be scientifically established to date. Given the relatively common incidence of GI complaints, it is not clear at this time whether this relates to a unique process in gut function or development that contributes to the common reports of GI issues in ASD.
Dr Margolis: There are probably a number of things that are associated with GI problems in individuals with ASD. Diet has been suggested as a cause, particularly a lack of dietary diversity.
Also, the gut and brain develop in many similar ways and along similar pathways; it is thus likely that the differences in brain development that occur in people with ASD are mimicked to some degree in the intestine. In the brain, these abnormalities translate into ASD-associated phenotypes such as differences in social and communication skills, while in the gut these can manifest as pain or issues with motility, such as constipation or diarrhea.
Additionally, a lot of psychiatric medications, which are commonly prescribed to people with ASD, cause off-target effects in the gut that can lead to GI problems.
How do GI symptoms affect behavioral and psychiatric symptoms and other outcomes in ASD?
Dr Goldman: The GI disorders in ASD can include a spectrum of symptoms. There are common reports of eating problems, such as restricted eating pattern with food selectivity, food refusal, and poor oral intake. ASD children are at risk for pica, constipation, chronic diarrhea, chronic abdominal pain, and gastroesophageal reflux disease.1
Interestingly, children with ASD with seizures, sleep disorders, and psychiatric problems tend to report more GI dysfunction. It is suggested that these issues may relate to autonomic nervous system dysfunction.1
Maladaptive comorbidities such as irritability and social withdrawal also tend to be associated with more reports of GI complaints, such as gas, abdominal pain, constipation, and diarrhea that may possibly contribute to behavioral issues.1
Dr Margolis: There is an increasing amount of data that show a link between GI symptoms and challenging behaviors, including self-injury, aggression, and even a worsening of the core diagnostic symptoms of ASD itself. Psychiatric symptoms and GI symptoms often coincide in non-ASD populations, and psychiatric comorbidities are common in ASD, so it is highly likely that these correlate as well.
What are some key recommendations for clinicians to screen for GI symptoms in this population?
Dr Goldman: Physicians and other health care providers need to be aware of the common association of GI complaints in ASD patients. At times, the diagnosis can be challenging in this population, who may be nonverbal and rely on nonverbal cues such tummy patting, pushing on tummy, and food refusal. Therefore, signs and symptoms that express their discomfort may include aggression, self-injury, irritability, abnormal vocalizations, or hyperactivity.1
The gold standard for diagnosing most of the common GI issues seen in ASD include the Rome criteria.1 In addition, the Autism Treatment Network has developed a GI symptom inventory that can help diagnose the common GI problems.7
Dr Margolis: GI problems are amongst the most common comorbidities in individuals with ASD. Given their high prevalence, as well as the strong links between challenging behaviors in ASD and GI symptoms, it is important to consider evaluation for GI issues in patients with ASD who present with challenging or worsening behaviors, especially those with a newer onset or increasing severity.
What are the most pressing remaining needs pertaining to this topic?
Dr Goldman: Future studies with research focusing on GI dysfunction and feeding concerns in ASD is a priority. Given the high prevalence of GI symptoms in ASD, addressing these issues starts with awareness amongst health care providers, followed by appropriate diagnosis and treatment strategies. Given the magnitude of the GI difficulties, there should be a low threshold for referral to a pediatric gastroenterologist.
Future directions include research into the relationship of behavioral factors with eating and toileting behaviors, and determining a possible physiologic cause, such as gut dysbiosis, gut sensory processing dysregulation, or food sensitivity.
Additional research is also warranted to elucidate the etiology, incidence, and treatment of GI problems in ASD, which are commonly interwoven with contributions from immune dysfunction, mucosal barrier issues, GI motility processes, and feeding and toileting concerns.
Dr Margolis: There are few, if any, really successful therapies for ASD. New treatments are thus a hugely pressing need. Given the links between diet, GI issues, and mood and behavior — not only in ASD but also increasingly in non-ASD populations — a better understanding of how diet affects the gut and behavior, and which components of the diet affect GI issues and behavior, are pressing questions that may lend insights into the development of novel therapeutic targets.
Other ways of targeting the gut and brain in ASD that have shown potential promise, including fecal microbiota transplant, need to be studied in a larger, multicenter, placebo-controlled setting. Finally, prospective, longitudinal intervention studies are key in assessing outcomes for all of these potential treatments.
References
- Madra M, Ringel R, Margolis KG. Gastrointestinal issues and autism spectrum disorder. Child Adolesc Psychiatr Clin N Am. 2020;29(3):501-513. doi:10.1016/j.chc.2020.02.005
- McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014;133(5):872-883. doi:10.1542/peds.2013-3995
- Leader G, Abberton C, Cunningham S, et al. Gastrointestinal symptoms in autism spectrum disorder: A systematic review. Nutrients. 2022;14(7):1471. doi:10.3390/nu14071471
- Fulceri F, Morelli M, Santocchi E, et al. Gastrointestinal symptoms and behavioral problems in preschoolers with autism spectrum disorder. Dig Liver Dis. 2016;48(3):248-254. doi:10.1016/j.dld.2015.11.026
- Chakraborty P, Carpenter KLH, Major S, et al. Gastrointestinal problems are associated with increased repetitive behaviors but not social communication difficulties in young children with autism spectrum disorders. Autism. 2021;25(2):405-415. doi:10.1177/1362361320959503
- Holingue C, Poku O, Pfeiffer D, Murray S, Fallin MD. Gastrointestinal concerns in children with autism spectrum disorder: A qualitative study of family experiences. Published online December 14, 2021. Autism. doi:10.1177/13623613211062667
- Margolis KG, Buie TM, Turner JB, et al. Development of a brief parent-report screen for common gastrointestinal disorders in autism spectrum disorder. J Autism Dev Disord. 2019;49(1):349-362. doi:10.1007/s10803-018-3767-7
This article originally appeared on Gastroenterology Advisor
