Gastrointestinal (GI) problems affect many children and adolescents with autism spectrum disorders (ASD). Access to rigorously studied treatments for medical conditions such as GI is a major unmet need for families. The Autism Speaks Autism Treatment Network (ATN) provides experts in the care and management of GI problems for these children and engages in clinical research. However, the underlying nature of GI dysfunction in ASD and its relationship to etiology and ASD symptoms are still poorly understood. This information is critical to developing better and more targeted treatments, so both clinical and basic research in this area is needed.
Given the importance this issue, Autism Speaks has recently announced a major Suzanne and Bob Wright Trailblazer Award for research into the biological mechanisms of GI disorders in ASD. (Read a press release about the award). The new study brings together innovative and cutting-edge pilot projects that form a new synergistic and coordinated effort. The connections between irregular bowel movements, gut barrier function, gut bacteria, immune function, and abnormal behavior have as yet not been investigated in ASD. This Trailblazer Study will examine these potential links.
We were privileged to have a chat with one of the key investigators on the study, Dr. Alessio Fasano, pediatric gastroenterologist at the University of Maryland School of Medicine (UMDSOM). He is professor of Pediatrics at UMDSOM and Director of the Center for Celiac Research and for the Mucosal Biology Research Center.
Autism Speaks: How many children with ASD are affected by GI disorders, and what are the most common problems they suffer from?
Dr. Fasano: The impact of GI problems in children with ASD is difficult to quantify since some of the symptoms, like stomachache or abdominal discomfort, cannot be communicated by nonverbal or minimally verbal children. For this reason, the percentage of ASD children suffering from GI symptoms reported in the literature varies from 9% to 90%. The most common GI symptoms include chronic constipation, stomachaches with or without diarrhea, and underwear soiling. Disturbed sleep patterns and nighttime waking also have been described as possibly secondary symptoms to gastroesophageal reflux (GERD).
Autism Speaks: Why is it important to study GI disorders specifically in children with ASD? Don’t we already know how to treat GI disorders in children?
Dr. Fasano: ASD is comprised of a mixed bag of different cases that share the behavioral description typical of ASD. In other words, ASD might be the “final destination,” but the route to get there can vary from individual to individual. Some children may reach their ASD destination through the “GI route,” meaning that it is possible that their GI disorders can lead to ASD in genetically susceptible individuals. By studying GI disorders specifically in children with ASD, we are not simply trying to develop methods for a better management of GI symptoms. Rather, we have a much more ambitious goal: We are trying to understand the underlying physiology of ASD; we are trying to “walk the same route” that these children took to arrive at their ASD “final destination.” By doing so, we hope to help them turn around and walk back from that ASD destination.
Autism Speaks: Please describe the study briefly in your own words.
Dr. Fasano: We believe that a few things are key ingredients of the ASD recipe: 1) Genetic predisposition (as suggested by twin studies); 2) Environmental triggers (nutrients, metals, additives, oxidants, to name just a few); and 3) An impaired gut barrier (leaky gut). Our studies will attempt to connect the dots among these three elements by 1) establishing whether the composition of intestinal bacteria in children with irregular bowel movements is different in ASD and non-ASD children and 2) whether this difference activates specific metabolic pathways leading to an immune response causing inflammation and, consequently, behavioral changes in genetically susceptible individuals. We will integrate our clinical studies in ASD children with a mouse model of autism, not only to validate our clinical findings but also to explore the possibility of specific interventions to modify the gut bacteria in order to alleviate the ASD-related behavior.
Autism Speaks: If our ultimate goal is to find appropriate treatments for GI disorders in children with ASD, why spend so much effort on studying the biology of the GI dysfunction?
Dr. Fasano: It is my humble opinion that a better understanding of the biology of GI dysfunctions that afflict many ASD children is the key to unbundling the complicated path that brought them to ASD. By answering some of these fundamental questions, we can follow the “bread crumbs” that they left behind during the journey toward their ASD final destination.
Autism Speaks: What are the top three things that we will be able to learn from the study?
Dr. Fasano: We will be able to answer the following three fundamental questions:
- Is there a specific composition of “bad bacteria” that can lead to a leaky gut and inflammation, and consequently, to ASD in genetically predisposed children?
- If this is the case, do these bad bacteria activate specific metabolic pathways so that we can search for metabolites that can be used as biomarkers (i.e., red flags) indicating that they embarked upon a journey that led to ASD?
- Can we manipulate the bacterial composition in the gut of children with GI disorders in order to correct the leaky gut and inflammation (by monitoring the disappearance of the metabolic biomarkers) and consequently, improve their behavior?
Autism Speaks: What are some signs that families and their doctors can look for if they think a child has a GI problem?
Dr. Fasano: Besides the obvious signs and symptoms (diarrhea, constipation, and underwear soiling), specific behaviors may point toward GI problems, including vocal behaviors (screaming, frequent clearing of throat, tics, swallowing, sighing, whining, moaning, etc.), motor behaviors (unusual posture, pressure on the belly, wincing, constant eating, gritting teeth, etc.), and/or changes in the overall state (sleep disturbances, non-compliance with requests that typically elicit proper response, increased irritability, etc.).
Autism Speaks: What can families do now if they think their child has a GI problem?
Dr. Fasano: If GI problems are suspected, families should be referred to a pediatric GI specialist familiar with ASD-related GI disorders. One thing to avoid is undertaking any conventional or unconventional remedy to solve their child’s GI issues without medical advice. Any intervention will complicate the interpretation of the underlying GI problems and, therefore, complicate the proper management needed to alleviate the child’s discomfort.