Many children and adolescents with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but the etiology is not well understood. Studies have shown conflicting evidence on whether there are nutritional deficiencies in the various diets of individuals with ASD. However, little is known about the relationship between dietary intake and GI symptomatology in ASD. The goal of the present study was to assess for potential relationships between GI symptoms and nutrient intake from diet in the same sample of individuals from the previous study, and to determine whether dietary differences might have contributed to our previously observed findings of a relationship between stress responses and GI functioning in ASD

Altstein, L. L.

Bauman, M. L.

Belenchia, A.

Beversdorf, D. Q.

Davis, D. J.

Ferguson, B. J.

Gillespie, C. H.

Hartnett, K.

Lee, E. B.

Macklin, E. A.

Margolis, K. G.

Marler, S.

Mazurek, M. O.

McDonnell, E.

McLaughlin, A.

Peterson, C. A.

Severns, D. S.

Veenstra-VanderWeele, J.

English

University of Missouri: MOspace

ResultsIntroduction• Many children and adolescents with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but the etiology is not well understood.• Studies have shown conflicting evidence on whether there are nutritional deficiencies in the various diets of individuals with ASD. However, little is known about the relationship between dietary intake and GI symptomatology in ASD.• Many patients with ASD try gluten-free and/or casein-free diets, and there is anecdotal evidence of improvement in ASD symptoms with dietary those dietary regimens.• A previous study conducted by this group has suggested an association between autonomic function and stress response with lower GI symptomatology. • The goal of the present study was to assess for potential relationships between GI symptoms and nutrient intake from diet in the same sample of individuals from the previous study, and to determine whether dietary differences might have contributed to our previously observed findings of a relationship between stress responses and GI functioning in ASD.ResultsGastrointestinal Symptoms• The most frequently occurring GI disorders in the sample were functional constipation (42.5%), irritable bowel syndrome (11.7%), lower abdominal pain associated with bowel symptoms (9.2%), and upper pain associated with bowel symptoms (7.5%).  See Table 1.Stress response• A significant positive relationship was found between cortisol response to stress and a greater lower GI tract score. See Table 2.• Presence of regressive ASD significantly modified the relationship between lower GI tract score and cortisol response to stress. See figure 1.• A significant positive correlation was identified between cortisol response to stress and FSIQ. See Figure 2.Dietary nutrient intake• Upper GI tract symptoms were significantly correlated with total dietary fiber intake and vitamin B6 intake; however, these relationships did not survive correction for multiple comparisons (Bonferroni Correction). See Table 4.• There were no significant associations between lower GI tract symptoms and dietary intake.DiscussionLower GI tract symptoms were positively associated with post-stress cortisol concentration.• This association was greater for children with a history of regressive ASD.Nutritional intake is not associated with GI symptomatology in this sample of individuals with ASD.• This supports the hypothesis that there may be other factors associated with the lower GI disorders in ASD, such as increased stress response.• Diet is also therefore not likely a driving factor for the previously observed relationship between stress responses and GI functioning in ASD.• Further studies are needed to explore non-diet associations with GI disorders in ASD.MethodsParticipants• 75 individuals with ASD were recruited through the Autism Speaks – Autism Treatment Network (ATN) and through clinic at the University of Missouri Thompson Center for Autism & Neurodevelopmental Disorders. See Table 1 for descriptive statistics. Assessment of Gastrointestinal Symptoms• Gastrointestinal symptoms were assessed using the Questionnaire on Pediatric Gastrointestinal Symptomatology-Rome III (QPGS-RIII). A scoring rubric was used to create continuous variables for upper and lower GI tract symptoms.Assessment of stress response• Cortisol response to tactile stimulation was utilized as a measure of stress response in these individuals. See Table 2.Assessment of Dietary intake• Dietary intake of each individual was assessed using a Food Frequency Questionnaire, adopted from a study on Omega-3 intake in cardiac patients by Ritter-Gooder PK et al., in which respondents estimate his/her food intake over the past month.• Responses were analyzed for nutritional intake using the online, publicly available USDA Food Composition Database that provides nutrient information for a given food.• Nutrient information for each food marked on a subject’s Food Frequency Questionnaire was obtained, and total nutrient intake for each subject was summed to give monthly nutrient intake. See Table 3.AcknowledgementsThis project was supported by University of Missouri School of Medicine Summer Research fellowship, as well as by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under cooperative agreement UA3 MC11054 – Autism Intervention Research Network on Physical Health. This information or content and conclusions are those of the author and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS or the U.S. Government. This work was conducted through the Autism Treatment Network serving as the Autism Intervention Research Network on Physical Health.Working collaboratively across North America, to address the physical health of children and adolescents with autism.Associations between nutrient intake and gastrointestinal symptoms in autism spectrum disorderD.S. Severns1, B.J. Ferguson2,6, S. Marler3, L.L. Altstein4, E.B. Lee5, M.O. Mazurek6,8, A. McLaughlin7, K. Hartnett17, E.A. Macklin4,9, E. McDonnell4, D.J. Davis15, A. Belenchia16, C.H. Gillespie15, C.A. Peterson16, M.L. Bauman10, K.G. Margolis11, J. Veenstra-VanderWeele12,13, & D.Q. Beversdorf2,6,141School of Medicine, University of Missouri; 2Interdisciplinary Neuroscience Program, University of Missouri; 3Department of Child and Adolescent Psychiatry, Vanderbilt University Medical Center; 4Massachusetts General Hospital Biostatistics Center; 5Departments of Pediatrics, Psychology, and Psychiatry, Vanderbilt University; 6The Thompson Center for Autism and Neurodevelopmental Disorders, University of Missouri; 7University of Missouri School of Medicine; 8Department of Health Psychology, University of Missouri; 9Harvard Medical School; 10Boston University School of Medicine; 11Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Columbia University; 12Department of Psychiatry and Sackler Institute for Developmental Psychobiology, Columbia University; 13New York State Psychiatric Institute; 14New York Presbyterian Hospital Center for Autism and the Developing Brain; 15William and Nancy Thompson Chair in Radiology, Departments of Radiology, Neurology, and Psychological Sciences, University of Missouri; 16Department of Veterinary PathobiologyBiomarker CovariateCorrelation (95% CI) p-value nCortisol Response(ln [post stress – pre stress])Upper GI Score -0.00 (-0.24, 0.23) 0.9755 75Lower GI Score 0.27 (0.04, 0.47) 0.0207 75FSIQ 0.27 (0.02, 0.49) 0.0365 64ABC Inappropriate Speech -0.27 (-0.47, -0.04) 0.0231 74ABC Hyperactivity -0.28 (-0.48, -0.05) 0.0186 74Figure 1. Illustration of the effect modification of history of regressive autism on the relationship between cortisol stress response and lower gastrointestinal tract scores Table 2. Partial Pearson correlations between Cortisol response and QPGS Rome III GI scores, FSIQ, and selected ABC and Vineland variables, controlling for age, gender, and cortisol pre-stress values (cortisol response only).  Significant correlations are in bold (p<0.05). % (n)Mean (SD) Range NMales 89.3%  (67) 75Age at Consent (Years)12.56  (3.7) 5-18 75Table 1. Demographics for sex and age.Figure 2. Impact of effect modifiers on the ANS-gastrointestinal symptomatology relationships. (A) effect of presence or absence of anxiety on relationship between lower GI tract scores and pNN50 baseline. (B) Effect of presence or absence of history of regression/loss of skills on the relationship between lower GI tract scores and pNN50 baselineTable 3. Mean nutrient intake valuesMean SD NRome III GI Upper Score 4.64 5.51323 75Rome III GI Lower Score 20.28 13.48128 75Water (g) 16572.9673 11460.771 75Energy (kcal) 20488.0367 10495.7657 75Protein (g) 1173.5551 577.60532 75Total Lipid Fat (g) 839.2664 471.00048 75Carbohydrate (By Difference; g) 2155.6363 1280.66155 75Dietary Fiber (Total; g) 236.2797 170.27214 75Sugars (Total; g) 903.4632 766.04648 75Calcium (mg) 18807.42 16132.6032 75Iron (mg) 124.2673 83.14305 75Magnesium (mg) 4071.2 2601.42227 75Phosphorous (mg) 21675.0833 13352.8603 75Potassium (mg) 43572.57 26575.607 75Sodium (mg) 26558.4067 16553.7216 75Zinc (mg) 158.421 86.6629 75Vitamin C (Total Ascorbic Acid; mg) 1460.161 1742.43404 75Thiamin (mg) 17.1451 9.35754 75Riboflavin (mg) 28.6636 20.36107 75Niacin (mg) 267.6509 135.11402 75Vitamin B6 (mg) 36.2633 29.69813 75Folate (DFE; µg) 4106.6433 3945.33584 75Vitamin B12 (µg) 79.5947 52.5026 75Vitamin A (RAE; µg) 8888.3467 7170.05499 75Vitamin A (IU) 69048.1067 73514.2181 75Vitamin E (Alpha Tocopherol; mg) 110.1635 79.68801 75Vitamin D2 + D3 (µg) 84.8217 79.3749 75Vitamin D (IU) 3410.783 3262.99249 75Vitamin K (Phylloquinone; µg) 1109.334 1096.80656 75Total Saturated Fatty Acids (g) 283.1597 168.1027 75Total Monounsaturated Fatty Acids (g) 308.1146 191.03401 75Total Polyunsaturated Fatty Acids (g) 176.6071 106.67456 75Total Trans Fatty Acids (g) 8.317 11.99395 75Cholesterol (mg) 3314.1667 1822.61335 75Rome III Upper GI ScoreRome III Lower GI ScoreRome III Upper GI Score 1 .531**Rome III Lower GI Score .531** 1Water (g) 0.013 0.103Energy (kcal) -0.004 0.102Protein (g) -0.081 0.063Total Lipid Fat (g) -0.111 0.011Carbohydrate (By Difference; g) 0.129 0.178Dietary Fiber (Total; g) .235* 0.168Sugars (Total; g) 0.224 0.132Calcium (mg) -0.055 0.085Iron (mg) 0.088 0.088Magnesium (mg) -0.017 0.085Phosphorous (mg) -0.067 0.085Potassium (mg) 0.01 0.117Sodium (mg) -0.028 0.071Zinc (mg) -0.002 0.106Vitamin C (Total Ascorbic Acid; mg) 0.17 0.098Thiamin (mg) 0.016 0.152Riboflavin (mg) -0.083 0.078Niacin (mg) -0.089 0.024Vitamin B6 (mg) 0.338** 0.184Folate (DFE; µg) 0.033 0.083Vitamin B12 (µg) -0.07 0.034Vitamin A (RAE; µg) -0.076 0.05Vitamin A (IU) 0 0.056Vitamin E (Alpha Tocopherol; mg) -0.032 0.005Vitamin D2 + D3 (µg) -0.202 -0.043Vitamin D (IU) -0.203 -0.044Vitamin K (Phylloquinone; µg) 0.107 0.106Total Saturated Fatty Acids (g) -0.073 0.029Total Monounsaturated Fatty Acids (g) -0.119 0.009Total Polyunsaturated Fatty Acids (g) -0.162 -0.031Total Trans Fatty Acids (g) -0.096 0.106Cholesterol (mg) -0.061 0.01Table 4. Correlation matrix between nutrient intake values and QPGS Rome III GI scores

Associations between nutrient intake and gastrointestinal symptoms in autism spectrum disorder

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Associations between nutrient intake and gastrointestinal symptoms in autism spectrum disorder

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