Friday, May 21, 2010
Franklin Hall B Level 4 (Philadelphia Marriott Downtown)
1:00 PM
Background:
Microbial translocation (MT) results from permeation of bacteria or microbial byproducts from the lumen of mucosal barriers such as the gastrointestinal (GI), respiratory or urinary tract into the bloodstream. MT is thought to result from enteropathies and inflammatory disorders of the GI tract that increase permeability of the mucosa or a “leaky gut”. In turn, MT is postulated to produce systemic immune activation which results in dysfunction of the central nervous system (CNS). Autistic individuals have been reported to have increased rates of GI abnormalities, including increased mucosal permeability, leading some to postulate that at least some individuals with autism may develop the neurodevelopmental symptoms as a secondary manifestation of MT resulting from a “leaky gut”.
Objectives:
To assess the role of MT in patterns of immune activation and evaluate MT serum markers among children with autism (AUT) and typically developing controls (TYP) and to examine the relationship of MT to developmental regression by comparing those with a history of regression (AUT-R) to those without a regression history (AUT-NR).
Methods:
Evidence for MT was examined in the sera from 57 children with autism, [23 AUT-R (mean age 4.38 yrs) and 34 AUT- NR (mean age 4.29 yrs)], and 33 TYP child (mean age 3.5 yrs)] All were participants in a longitudinal study of clinical and immunological factors associated with autism. Autism was diagnosed using the ADI-R and ADOS as well as clinical judgment. Regression history was also assessed using the Regression Validation Interview. Regression was defined as language loss and/or loss of social engagement. Markers for MT included lipopolysacharide (LPS - a component of Gram negative bacteria cell walls), LPS-binding protein (LBP) and anti-endotoxin core immunoglobulins IgG and IgM. Circulating levels of MT markers were determined in sera: LPS were determined by the limulus amebocyte lysate assay and LBP and anti-endotoxin core IgG and IgM antibodies were quantified with ELISA assays. Wilcoxon’s signed-rank test was used for statistical analysis of significance.
Results:
No significant differences in circulating levels of LPS were observed between the AUT and TYP groups (p=0.161); or between the AUT-R and AUT-NR groups (p=0.974). LBP levels did not differ significantly between the AUT and TYP groups (p=0.056 with trend towards TYP>AUT) or AUT-R vs. AUT-NR group (p=0.24).Similarly, the anti-endotoxin core IgG and IgM antibodies levels showed no significant differences between the AUT and TYP groups (p=0.913 and 0.418 respectively)
Conclusions:
Circulating levels of MT markers did not differ significantly between children with autism and age-matched typical controls, nor did a history of regression correspond to evidence of circulating MT markers. These observations suggest that MT is not a common physiopathological response in children with autism and fail to provide support the hypothesis of “leaky gut” associated with autistic symptomatology.
Microbial translocation (MT) results from permeation of bacteria or microbial byproducts from the lumen of mucosal barriers such as the gastrointestinal (GI), respiratory or urinary tract into the bloodstream. MT is thought to result from enteropathies and inflammatory disorders of the GI tract that increase permeability of the mucosa or a “leaky gut”. In turn, MT is postulated to produce systemic immune activation which results in dysfunction of the central nervous system (CNS). Autistic individuals have been reported to have increased rates of GI abnormalities, including increased mucosal permeability, leading some to postulate that at least some individuals with autism may develop the neurodevelopmental symptoms as a secondary manifestation of MT resulting from a “leaky gut”.
Objectives:
To assess the role of MT in patterns of immune activation and evaluate MT serum markers among children with autism (AUT) and typically developing controls (TYP) and to examine the relationship of MT to developmental regression by comparing those with a history of regression (AUT-R) to those without a regression history (AUT-NR).
Methods:
Evidence for MT was examined in the sera from 57 children with autism, [23 AUT-R (mean age 4.38 yrs) and 34 AUT- NR (mean age 4.29 yrs)], and 33 TYP child (mean age 3.5 yrs)] All were participants in a longitudinal study of clinical and immunological factors associated with autism. Autism was diagnosed using the ADI-R and ADOS as well as clinical judgment. Regression history was also assessed using the Regression Validation Interview. Regression was defined as language loss and/or loss of social engagement. Markers for MT included lipopolysacharide (LPS - a component of Gram negative bacteria cell walls), LPS-binding protein (LBP) and anti-endotoxin core immunoglobulins IgG and IgM. Circulating levels of MT markers were determined in sera: LPS were determined by the limulus amebocyte lysate assay and LBP and anti-endotoxin core IgG and IgM antibodies were quantified with ELISA assays. Wilcoxon’s signed-rank test was used for statistical analysis of significance.
Results:
No significant differences in circulating levels of LPS were observed between the AUT and TYP groups (p=0.161); or between the AUT-R and AUT-NR groups (p=0.974). LBP levels did not differ significantly between the AUT and TYP groups (p=0.056 with trend towards TYP>AUT) or AUT-R vs. AUT-NR group (p=0.24).Similarly, the anti-endotoxin core IgG and IgM antibodies levels showed no significant differences between the AUT and TYP groups (p=0.913 and 0.418 respectively)
Conclusions:
Circulating levels of MT markers did not differ significantly between children with autism and age-matched typical controls, nor did a history of regression correspond to evidence of circulating MT markers. These observations suggest that MT is not a common physiopathological response in children with autism and fail to provide support the hypothesis of “leaky gut” associated with autistic symptomatology.