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Title:Nutrition and the GI microbiota in children with autism spectrum disorder and impact on symptom severity
Author(s):Harold, Kirsten Berding
Director of Research:Donovan, Sharon M
Doctoral Committee Chair(s):Dilger, Ryan N
Doctoral Committee Member(s):Miller, Michael J; Holscher, Hannah D; Cohen, Amy P
Department / Program:Nutritional Sciences
Discipline:Nutritional Sciences
Degree Granting Institution:University of Illinois at Urbana-Champaign
Abstract:The gastrointestinal (GI) microbiota is increasingly recognized for its ability to influence brain function and behavior. In children with Autism Spectrum Disorder (ASD), a microbial dysbiosis has been described and some bacterial taxa were found to predict certain symptoms of ASD. Additionally, picky eating behavior and food aversions are common in children with ASD, resulting in limited diet variety and decreased nutrient intake (e.g., fiber). Diet is one of the major determinants of the GI microbiota; however, previous studies have not systematically investigated the role of diet in shaping the GI microbiota in children with ASD. Likewise, overall microbial stability is recognized as more beneficial due to its ability to protect against pathogen invasion and maintain overall function. In children with ASD little is known about the stability of the microbiota. Therefore, the goal this dissertation research was to assess the impact of diet on the GI microbiota in children with ASD and microbial stability over a 6-month period with the following aims :1) to investigate differences in microbiota composition and volatile fatty acid (VFA) concentration between children with ASD and unaffected controls and investigate the relationship to ASD symptoms; 2) to determine the effect of long-term dietary patterns and short-term nutrient intake on the fecal microbial composition and VFA concentration in children with ASD and uncover relationships between diet, fecal microbiota, VFAs and ASD symptoms; and 3) to analyze the microbiota composition and VFA concentrations in children with ASD and unaffected controls over a 6-month period and identify dietary factors that correlate with a more stable microbial profile. Children with ASD (ASD; n=26) and age- and sex-matched unaffected controls (CONT; n=32) were recruited in the Midwest area. Fecal samples, a 3-day food diary, a food frequency questionnaire, and an online questionnaire collecting information on demographics, GI health, nutrition supplement use were collected at baseline, 6-weeks post-baseline and 6-months post baseline. ASD symptoms were assessed using the Pervasive Developmental Disorder Behavior Inventory – Screening Version (PDDBI-SV). Bacterial DNA was analyzed using 16S rRNA sequencing and quantitative Polymerase Chain Reaction. VFA concentrations were analyzed by gas chromatography. Dietary patterns were derived from the Youth and Adolescence Food Frequency Questionnaire (YAQ) using Principal Component Analysis and exploratory Factor Analysis. Nutrient intake was assessed by the Nutrition Data System for Research. All data were analyzed using SAS 9.4. Differences in microbiota composition between ASD and CONT were observed. Overall, β-diversity assessed by permutational multivariate analysis (PERMANOVA) differed (p=0.02) based on unweighted but not weighted d UniFrac. α-diversity measured as observed Operational Taxonomic Units (OTUs) tended to be higher (p=0.08) in ASD. Microbial abundances on the phyla, family, order and genera level were observed. Namely, ASD had higher levels of Firmicutes, Clostridiales, Clostridiaceae, Peptostreptococcaceae, Coriobacteriaceae, Clostridium, SMB53, Blautia, and Roseburia, but lower levels of Bacteroidetes, Streptophyta, Rikenellaceae, Butyricimonas, Butyrivibrio, Faecalibacterium, Dialister, and Bilophila compared to CONT. Furthermore, higher concentrations of acetate, propionate and butyrate were detected in ASD. Lastly, Peptostreptococcaceae and Faecalibacterium predicted social deficit (SOCDEF) scores in children with ASD as measured by the PDDBI-SV. Investigating dietary intake revealed that children with ASD consumed lower amounts of insoluble fiber, pectin, vitamin C and dairy, but consumed more snacks and sweets than unaffected children. To analyze the impact of nutrition on the GI microbiota, four analyses were utilized. First, correlation analyses revealed that nutrient and food group intake were associated with the abundance of bacterial taxa. Second, children with ASD characterized as picky eaters or having a repetitive eating pattern harbored a unique microbial composition. Third, two dietary patterns (DP) were empirically derived for children with ASD using the YAQ. DP-1, characterized by intakes of vegetables, starchy vegetables, legumes, nuts and seeds, fruit, grains, juice and dairy, was associated with lower abundance of Enterobacteriaceae, Lactococcus, Roseburia, Leuconostoc, and Ruminococcus. DP-2, characterized by intakes of fried foods, Kid’s meals, condiments, protein foods, snacks and starchy foods, was associated with higher abundance of Barnesiellaceae, Alistipes, and lower abundance of Streptophyta as well as higher concentrations of propionate, butyrate, isobutyrate, valerate, and isovalerate. Diet-induced microbial comppsition was related to some GI symptoms, but was not related to SOCDEF scores. Lastly, moderation analysis did not reveal a significant interaction between microbial taxa and dietary components in prediction SOCDEF scores. To investigate the temporal microbial stability, two additional samples collected over a 6-month period were analyzed for microbiota composition and VFA concentration. We found that overall the microbiota composition and metabolites concentration varied in children with ASD and variability in community membership negatively correlated with median SOCDEF scores. Furthermore, different bacteria taxa contributed to a stable microbiota profile in each group. Clostridiales, Ruminococcaceae, Lactococcus, Turicibacter, Dorea, and Phascolarctobacterium contributed to a more stable microbiota community in children with ASD whereas Barnesiellaceae, Adlercreutia, Faecalibacterium, Sutterella and Bilophila contributed more in to a stable microbiota in CONT children. Lastly, GI microbiota variability was related to habitual dietary patterns. Overall, the results presented herein contribute to the growing literature on a microbial dysbiosis and the impact of specific microbial taxa on symptoms in children with ASD. Importantly, this research offers new insight into the effect of diet on the microbiota composition, microbial metabolism and the temporal variability in children with ASD. Future studies are warranted to analyze whether dietary intake could potentially be a modifiable moderator of the microbiota-symptoms connections in ASD.
Issue Date:2018-07-11
Rights Information:Copyright 2018 Kirsten Berding Harold
Date Available in IDEALS:2018-09-27
Date Deposited:2018-08

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