There has been a lot of concern that abnormal GI function contributes to both behavioral and gastrointestinal symptoms in children with autism.  To categorize some of these problems, the term ‘leaky gut’ has been used.

An upcoming study (RI Kushak et al. JPGN DOI: 10.1097/MPG.0000000000001174) (thanks to Ben Gold for forwarding this reference) examines this issue. Using a case-control design, pediatric patients with autism spectrum disorder (ASD) (n=61) were compared with 50 children with normal development.

Workup:

• Endoscopy (EGD and colonoscopy) with histologic analysis
• Disaccharidase analysis
• Intestinal permeability studies with lactulose and rhamnose
• Fecal biomarkers: calprotectin and lactoferrin

According to the authors, all of the study subjects underwent endoscopy and “all had clinical indications for diagnostic endoscopy.”  Most common indications were parental reports of abdominal pain and diarrhea.

Key findings:

• Disaccharidase activity levels were not significantly different between the groups. In agreement with prior studies, there was frequent lactase deficiency, with 66% of ASD children in this study with deficient enzyme activity (<15 μmol/min/g).  However, lactase activity in the children with ASD was not lower than the non-ASD children.
• There were no significant differences in measures of intestinal permeability.  Normative values for lactulose and rhamnose ratio are not definitively established.  However, when using similar cutoff ratios, there were similar results in both groups.

Calprotectin:

• Intestinal inflammatory markers (calprotectin/lactoferrin) were not significantly different, after the authors excluded the five “neurotypical” children who were diagnosed with inflammatory bowel disease.
• For calprotectin, the authors considered a level <50 mcg/g to be normal.  In the ASD group, 31of 49 (63%) had abnormal calprotectin compared with 19 of 31 (61%) in the non-ASD group.
• For calprotectin levels >150 mcg/g, 9 of 49 (18%) reached this level in the ASD group and 8 of 31 (26%) in the non-ASD group.

Histology:

• Similar levels of GI tract inflammation were noted in both groups –generally mild.
• In the ASD group, 32 (52%) had inflammation somewhere in their GI tract, “but it was generally mild and non-diagnostic.”  In the ASD group, five had features consistent with GERD, two had eosinophilic esophagitis (EoE).  There were 12 (19%) who had colonic inflammation and 3 (5%) with ileal inflammation.  None had celiac disease or H pylori.
• In the non-ASD group, four had EoE, four (8%) had ileal inflammation, and nine (18%) had colonic inflammation.  The authors noted Crohn’s disease in three and a total of five children with IBD.

My take:

1. This study suggests that symptomatic children with autism have similar (and probably not worse) GI problems as neurotypical children.  The idea that children with autism have a more leaky gut than children without autism is quite dubious based on these results.
2. The biggest problem for GI physicians is not addressed in this study and involves children with and without autism: appropriate selection for evaluation.  While the authors chose children with “clinical indications,” these, in fact, are often subjective and with permissive interpretation could be used to justify endoscopy in 40% of children.
3. Another huge problem is interpretation of abnormal results.  While the authors report large numbers with intestinal inflammation in both groups, most of this was considered to be insignificant clinically.  How should trivial inflammation be reported in studies?  This problem is not unique to this study and makes it difficult to assess the value of endoscopy more broadly.

Related blog posts:

• Gluten-free, Casein-free -No Improvement in Autism …
• Taking Folic Acid for Autism Prevention | gutsandgrowth
• Another Big Study: No Link between MMR vaccine and Autism …
• “Too many vaccines and autism” is debunked | gutsandgrowth
• Autism Earlier -Gazing for Clues | gutsandgrowth

Law Quad, Univ Michigan