Environmental Factors Associated with Autism Spectrum Disorder: A clinical study of microflora and micronutrient abnormalities

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Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterised by impaired socialisation. The current project examines the hypothesis that ASD represents a broad range of distinct disease processes typified by environmental insult(s) during a period crucial for the development of any of the systems responsible for social integration skills, sharing simply the fundamental disruption to social functioning with various, definable systemic pathologies related to the initial insult conferring the heterogeneity of the condition. ASD will therefore have both modifiable environmental factors relating to the aetio-pathogenesis of the condition and likely, remediable disease processes. Following an examination of the relevant literature this project presents the Variable Insult Model of Autism. As part of a wider research strategy, this project goes on to explore potential modifiable environmental factors in patients with ASD.Zinc deficiency was explored as a potential environmental modifiable factor involved in the pathophysiology of autism and co-morbid disease. 72 patients with ASD were compared with 234 non-ASD controls. Mean serum zinc levels in the ASD group vs. the control group were 10.01 umol/l (SD 1.52 umol/l) vs. 11.61 umol/l (SD 2.14 umol/l, with a statistically significant difference - p < 0.0001, CI 1.2 – 2.1). The findings withstood correction for age and sex, and zinc did not correlate with diet or supplement use in the ASD group. Total lymphocyte count increased as zinc increased in the ASD group with zinc levels of 10.5 umol/l or above, suggesting zinc status is poor in patients with autism and this is affecting immune function. Urinary metabolomics, quantitative PCR stool analysis and autonomic function were also explored in ASD, as biomarkers of systemic disease processes presenting potential modifiable factors. The urinary organic acids of 49 patients were analysed versus population norms. 90% of patients with ASD had at least one abnormality. A follow-up study of 122 patients revealed succinic acid and 2-hydroxyhippuric acid were significantly raised in the ASD group versus population means (p = < 0.0001 and <0.0001 respectively). Quantitative PCR analysis was conducted on 29 patients with autism versus 7 age-matched controls. Firmicutes to Bacteriodetes ratio was significantly elevated in the autism group versus the controls 69:41 (SD 8) vs. 54:46 (SD 8) (p < 0.003). A follow-up study of 143 patients and 12 controls showed consistent abnormalities in the composition of firmicutes and bacteriodetes (p = 0.005) and this withstood correction for age and sex (p = 0.009), suggesting an on-going abnormality in gut flora composition in the ASD-cohort. Autonomic profiles were available in 45 patients with ASD. There was marked variability in vagal tone, however in 11 patients with ASD who had both autonomic profile and qPCR stool analysis there was suggestion of a positive correlation between vagal tone and microflora composition (represented by firmicutes to bacteriodetes ratio) (p < 0.003).In summary, evidence suggests there are modifiable environmental factors associated with the aetiology, pathophysiology and disease evolution in ASD, and this is worthy of further consideration and investigation. From the preliminary results presented here, zinc status is poor in ASD and may be affecting immune function; gut flora abnormalities appear common and may be affecting neurological function in ASD.

Keyword(s)

autism; autonomic; environment; immune; microflora; vagal tone; zinc

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