The Potential Role of Probiotics in the Management of Childhood Autism Spectrum Disorders

Autism spectrum disorders (ASD) are defined by impairments in verbal and non-verbal communication, social interactions, and repetitive and stereotyped behaviours. In addition to these core deficits, previous reports indicate that the prevalence of gastrointestinal (GI) symptoms ranges widely in individuals with ASD, from 9 to 91% in different study population.[1]

The role of probiotics in the management and treatment of these alterations has been explored in a recent free access paper, published in Gastroenterology Research and Practice Oct 2011.[2]

The mucosal immune system in individuals with autistic spectrum disorder (ASD) appears to suffer a variety of aberrations, which in turn may contribute to aspects of the symptoms and functional disturbances experienced by Autistic individuals.

Reported functional disturbances include increased intestinal permeability,[3] deficient enzymatic activity of disaccharidases,[4] increased secretin-induced pancreatico-biliary secretion,3 and abnormal faecal Clostridia taxa.[5] Some children placed on exclusion diets or treated with the antibiotic vancomycin are reported to improve in cognitive and social function.[6],[7] Furthermore, a recent study found a strong correlation between GI symptoms and autism severity.[8]

Macroscopic and histological observations in ASD include findings of ileo-colonic lymphoid nodular hyperplasia, enterocolitis, gastritis, and esophagitis.[9],[10],[11],[12]Associated changes in intestinal inflammatory parameters include higher densities of lymphocyte populations, aberrant cytokine profiles, and deposition of immunoglobulin (IgG) and complement C1q on the basolateral enterocyte membrane.[13]

Despite the evidence linking the incidence of GI symptoms to ASD its use as a diagnostic tool – that is the defining of a GI symptom and the presence of and ASD diagnosis appears to have little correlation and is not recommended.[14],[15]

A paper published in the Journal of Leukocyte Biology in 2006 recognised that the immune aberrations seen in individuals with ASD represented a new area of investigation and treatment, with the gastrointestinal tract offering a point of intervention that could provide positive outcomes.[16]

Metagenomic analysis of intestinal bacteria has uncovered compositional dysbiosis manifesting as decreases in Bacteroidetes, increases in the ratio of Firmicutes to Bacteroidetes, and increases in Betaproteobacteria. This suggests that the application of strategies to alter these ratios towards those seen in non ASD subjects may confer an immunological and digestive improvement that could be reflected in behavioural outcomes.

Comment

The role of probiotics in the interventions employed by practitioners, clinicians and patients relies largely on clinical feedback and immunological translation, as opposed to large RCT trials on patients with ASD. To assist colleagues in the comprehension of the potential role and application, I and 4 esteemed scientists reviewed the literature and based on extensive clinical experience and research published a short review paper in Gastroenterology Research and Practice journal providing free access.

References


[1] Buie T, Campbell DB, Fuchs GJ 3rd, Furuta GT, Levy J, Vandewater J, Whitaker AH, Atkins D, Bauman ML, Beaudet AL, Carr EG, Gershon MD, Hyman SL, Jirapinyo P, Jyonouchi H, Kooros K, Kushak R, Levitt P, Levy SE, Lewis JD, Murray KF, Natowicz MR, Sabra A, Wershil BK, Weston SC, Zeltzer L, Winter H. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. 2010 Jan;125 Suppl 1:S1-18. View Abstract

[2] J. William Critchfield, Saskia van Hemert, Michael Ash, Linda Mulder, and Paul Ashwood, “The Potential Role of Probiotics in the Management of Childhood Autism Spectrum Disorders,” Gastroenterology Research and Practice, vol. 2011, Article ID 161358, 8 pages, 2011. doi:10.1155/2011/161358 View Full Paper

[3] D’Eufemia P, Celli M, Finocchiaro R, Pacifico L, Viozzi L, et al. Abnormal intestinal permeability in children with autism. Acta Paediatr. 1996;85:1076–1079 View Abstract

[4] Horvath K, Papadimitriou JC, Rabsztyn A, Drachenberg C, Tildon JT. Gastrointestinal abnormalities in children with autistic disorder. J Pediatr. 1999;135:559–563. View Abstract

[5] Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005;54:987–991. View Abstract

[6] Knivsberg AM, Reichelt KL, Hoien T, Nodland M. A randomised, controlled study of dietary intervention in autistic syndromes. Nutr Neurosci. 2002;5:251–261 View Abstract

[7] Sandler RH, Finegold SM, Bolte ER, Buchanan CP, Maxwell AP, et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol. 2000;15:429–435 View Abstract

[8] Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism–comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 2011;11:22. View Abstract

[9] White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood) 2003;228:639–649. View Abstract

[10] Wakefield AJ, Anthony A, Murch SH, Thomson M, Montgomery SM, et al. Enterocolitis in children with developmental disorders. Am J Gastroenterol. 2000;95:2285–2295. View Abstract

[11] Furlano RI, Anthony A, Day R, Brown A, McGarvey L, et al. Colonic CD8 and gamma delta T-cell infiltration with epithelial damage in children with autism. J Pediatr. 2001;138:366–372. View Abstract

[12] Torrente F, Ashwood P, Day R, Machado N, Furlano RI, et al. Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism. Mol Psychiatry. 2002;7:375–382, 334. View Abstract

[13] Torrente F, Ashwood P, Day R, Machado N, Furlano RI, et al. Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism. Mol Psychiatry. 2002;7:375–382, 334. View Abstract

[14] Maenner MJ, Arneson CL, Levy SE, Kirby RS, Nicholas JS, Durkin MS. Brief Report: Association Between Behavioral Features and Gastrointestinal Problems Among Children with Autism Spectrum Disorder. J Autism Dev Disord. 2011 Oct 20. View Abstract

[15] Whitehouse AJ, Maybery M, Wray JA, Hickey M. No association between early gastrointestinal problems and autistic-like traits in the general population.Dev Med Child Neurol. 2011 May;53(5):457-62. doi: 10.1111/j.1469-8749.2011.03915.x. Epub 2011 Mar 21 View Abstract

[16] Ashwood P, Wills S, Van de Water J. The immune response in autism: a new frontier for autism research. J Leukoc Biol. 2006;80:1–15. View Abstract

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