New worlds to explore
Articles - Autism Articles
by Bernard Dixon
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http://infection.thelancet.com
Vol 6 February 2006 73
It is a century since microbiologists experienced such a sense of
adventure. Then, the early microbe hunters were incriminating one
organism after another as specific causes of human, animal, and plant
diseases. Others were isolating non-pathogens as agents of change in
the natural environment. Now, as molecular methods augment and
supplant classical techniques, revolution is afoot once more.
Throughout all sectors of microbiology, pure and applied, new worlds
are being explored and old problems addressed with greater precision.
Last month I wrote about the use of PCR to characterise the microbial
flora of aeroplanes. This month comes news of researchers harnessing
fluorescence in-situ hybridisation to clarify the possible involvement
of the gut flora in autistic disorders in children.
The notion behind this work has been around for several years,
triggered in part by clinicians who have discovered that many autistic
children have received several courses of antimicrobial therapy. There
has also been one re****t that vancomycin, given orally, can lead to
significant short-term improvements in patients receiving this
antibiotic (J Child Neurol 2000; 15: 429). Could antibiotic treatment
have modified the children=92s intestinal microflora in such a way as to
provoke the developmental problems that characterise autism?
Efforts to go beyond this anecdotal evidence have proved frustrating.
Indeed, the complexity of autism has bedevilled investigations into a
much wider range of possible causes. Autism is not a single condition
but a spectrum of abnormalities affecting a child=92s social,
communicative, and imaginative development. Known as autistic spectrum
disorders (ASDs), they are four times commoner in boys than girls.
There is limited evidence that gluten-free and possibly other
exclusion diets can help=97in two ways. First, some re****ts suggest that
the behaviour of youngsters consuming diets of this sort improves in
consequence. Second, removal of nutrients such as gluten or casein can
lead to a lessening of the gastrointestinal symptoms (abdominal pain,
bloating, and diarrhoea or constipation) that affect many autistic
children.
It is possible that these two effects are closely linked. However,
further understanding has awaited detailed comparisons of the
composition of the gut flora of people with ASD as compared with
healthy controls. A few authors have written about the likely role of
clostridia, for example, which can generate powerful neurotoxins. But
there have been no persuasive studies to substantiate the influence of
this or any other group of organisms.
Anne McCartney, Helena Parracho, and colleagues at the University of
Reading have now made an im****tant advance in our understanding. They
investigated 48 boys and ten girls (aged between 3 and 16), all of
whom had been diagnosed with ASDs, and compared their intestinal flora
with that of control individuals. Instead of culture methods, the
researchers used fluorescence in-situ hybridisation with
oligonucleotide probes targeting predominant components of the
intestinal flora.
The results, published in the Journal of Medical Microbiology (2005;
54: 987), show a significantly higher incidence of Clostridium
histolyti*** in the faecal flora of ASD patients than in healthy
children. There were no significant differences between the two groups
in total bacterial loads, nor in the incidence of bifidobacteria or
other potentially relevant organisms.
=93The numerically predominant bacterial population in samples from ASD
patients was C histolyti***
(Clostridium clusters 1 and 11)=94, the authors write. They have never
previously observed this type of phenomenon when investigating the
intestinal microbiology of human subjects suffering from conditions
such as ulcerative colitis, bowel cancer, or irritable bowel syndrome.
=93These results sup****t the hypothesis of an association between
clostridia and the development of certain autistic characteristics.=94
Whether the association is to any degree causal remains an open
question. However, the Reading findings are impressive, not least
because molecular approaches have enormous advantages over traditional
culture techniques. Even so-called selective methods are imperfect in
recovering relevant organisms, as well as being subject to problems
arising through the trans****t and storage of specimens.
The revolution gathers pace.
http://www.ei-resource.org/articles/autism-articles/new-worlds-to-explore/
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