Elsevier

Anaerobe

Volume 18, Issue 2, April 2012, Pages 260-262
Anaerobe

Pathogenesis and toxins
Microbiology of regressive autism

https://doi.org/10.1016/j.anaerobe.2011.12.018Get rights and content

Abstract

This manuscript summarizes some of our earlier work on the microbiology of autism subjects’ stool specimens, as compared with stools from control subjects. Our most recent data indicating that Desulfovibrio may play an important role in regressive autism is also presented. In addition, we present information on antimicrobial susceptibility patterns of Desulfovibrio using the CLSI agar dilution susceptibility technique. In addition, we summarize data from our earlier studies showing the impact of various antimicrobial agents on the indigenous bowel flora. This shows that penicillins and cephalosporins, as well as clindamycin, have a major impact on the normal bowel flora and therefore might well predispose subjects to overgrowth of such organisms as Clostridium difficile, and of particular importance for autism, to Desulfovibrio.

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

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