Incidence of Gastrointestinal Distress and Effects of Diet in 1- to 6-Month-Old Infants At High Risk for Autism Spectrum Disorders

Background: Gastrointestinal (GI) distress (constipation, diarrhea, vomiting, etc.) is reported to be co-morbid in children with Autism Spectrum Disorders (ASD) although its etiology is not well understood.  Preliminary evidence suggests that GI distress in ASD may be associated with “Leaky-Gut”, i.e. increased permeability of the intestinal mucosal barrier due to either delayed or abnormal development.  During normal digestion, the mucosal barrier is responsible for keeping the powerful digestive enzymes out of the intestinal wall.  If these degrading enzymes enter the wall of the intestine, they cause major damage to the intestinal wall, resulting in GI distress. Factors in breast-milk, such as somatostatin, have been hypothesized to protect the intestine by inhibiting the release of digestive enzymes while intestinal barrier is still developing.  In sum, we hypothesize that GI distress in association with ASD may result from an interaction between 1) increased permeability of the intestinal mucosal barrier and 2) diet.

Objectives: In the current study, we examined whether infants at “High-Risk” for ASD because they have an older sibling diagnosed with the disorder, show an elevated predisposition for GI distress (possibly due to Leaky-Gut), and whether this predisposition is affected by choice of diet.

Methods: Our sample included 38 “High-Risk” infants (from families with an older sibling with ASD) and 83 “Low-Risk” control infants (from families with an older sibling, but no ASD history).   Parents filled out extensive questionnaires about their infant’s GI history and diet, between the ages of 1- and 6-months.  They were asked to report on the absence/presence of GI problems that were serious enough to seek medical advice, and at what age this occurred.    They were also asked to report the infant’s diet history between 1- and 6-months, selecting one of three categories: breast-milk only (BMO), no breast-milk (NBM) and sometimes breast-milk (SBM). 

Results:  Across diet categories, the incidence of GI problems in High-Risk infants (47%) was 1.5-fold higher than in Low-Risk infants (33%).   These effects varied with diet category.  Whereas High- and Low-Risk infants exhibited about the same incidence of GI distress when fed a BMO diet (High-Risk = 25%, Low-Risk = 24%), when fed a NBM diet, GI problems in High-Risk infants (61.5%) were 2.9-fold higher (p = 0.034, chi-squared) than in Low-Risk infants (21.4%).  These effects were not driven by age, i.e., they were not due to infants tending to be younger in the BMO, than in the NBM, category.

Conclusions: The impact of a non-breast milk diet on GI distress is greater in High-Risk, than Low-Risk infants, with High-Risk infants showing atypically elevated GI distress when not on a BMO diet.  Such findings are consistent with the possibility that GI distress in association with ASD may result from an interaction between Leaky-Gut and diet early in development.  We are tracking biological markers of Leaky-Gut in these infants, which will help elucidate the nature of their GI distress and hopefully lead to effective early intervention.  Supported by NS071580.