Pathogenesis and toxinsMicrobiology of regressive autism
Section snippets
First evidence that bacteria are involved in regressive autism
Our interest in autism began with the publication by Ellen Bolte of a hypothesis in which she proposed that intestinal low-grade infection with Clostridium tetani (later changed to clostridia) might play an important role in the disease [5]. She proposed to Dr. Richard Sandler that he treat her autistic child with oral vancomycin since this drug was very active against clostridia and was virtually unabsorbed from the gut on oral administration. Her son had a remarkable improvement on this
Second piece of evidence that bacteria play a role in autism
Our laboratory studied stool specimens on these children and others and initially hypothesized that clostridia were indeed involved [7]. We also had the opportunity to study gastric juice and duodenal luminal fluid in a few patients [7]. Two patients were of particular interest; one had relative hypochlorhydria and the other severe hypochlorhydria without any obvious disease or medication to account for it; both had significant overgrowth of a wide variety of bacteria, primarily anaerobes. As
Third piece of evidence indicating bacteria are involved in autism
In Table 3, we see the organisms that are potentially important as contributing to autism, based on data from the pyrosequencing study. Followup studies using cultural techniques and real-time PCR ruled out Bacteroides vulgatus since it was found in roughly identical frequency in both autism subjects and control subjects. On the other hand, these two techniques revealed that Desulfovibrio was found in about 50% of autistic subjects, in some siblings of autistic children, and not at all in
Activity of antimicrobial drugs vs. Desulfovibrio and vs. normal bowel flora
In Table 5, we note that aztreonam, an oral beta-lactam compound thought to not have activity against anaerobes is actually moderately active vs. Desulfovibrio species. This compound is virtually not absorbed when given orally so levels in the bowel are relatively high (about 1000 mcg/gm) and there is virtually no toxicity; it is not cross-reactive with penicillins and cephalosporins so subjects allergic to those compounds can typically tolerate aztreonam well [17]. However, Desulfovibrio
Hypothetical pathogenesis of autism
The hypothetical pathogenesis of autism is outlined in Fig. 1. We believe that it is likely that most children who develop autism have an immunologic defect related to either environmental toxins or genetic factors. Antimicrobials lead to in-growth or overgrowth of Desulfovibrio species, as outlined above, and diet undoubtedly plays a major role in this phenomenon as well. Desulfovibrio may lead to direct damage to the host or there may be an autoimmune response. Key factors in the virulence of
References (19)
Autism and Clostridium tetani
Med Hypotheses
(1998)- et al.
Pyrosequencing study of fecal microflora of autistic and control children
Anaerobe
(2010) State of the art; microbiology in health and disease. Intestinal bacterial flora in autism
Anaerobe
(2011)- et al.
Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism
Am J Clin Nutr
(2004) - et al.
Low-grade endotoxemia in patients with severe autism
Neurosci Lett
(2010) - et al.
Changes in human intestinal flora related to the administration of antimicrobial agents
The most air-tight study in psychiatry? Vitamin B6 in autism
Autism Res.Rev.Int
(2000)Autism has high costs to U.S. Society
(2006)Autism and developmental disabilities monitoring (ADDM) network
(2008)
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