"The Role of the Gut Microbiome in Autism"
There are many examples in nature of
intestinal microbes altering host behavior.
One such example involves the brain parasite Toxoplasma.
When it infects a rodent through the gut,
it finds its way into the brain
and causes the animal to lose its innate fear
of the odor of bobcat urine.
Why does the parasite care about what mice are afraid of?
Because by not avoiding predators,
they’re more often caught and eaten;
so, the parasite can then go on
to infect other rodents.
If you’re a mouse brain parasite,
how are you going to spread?
Mice aren’t cannibals;
so, you have to make sure
the mouse you’re in is
eaten by something else.
So, the parasite evolved a way
to alter the mouse’s behavior.
Given the potential power of
microbes to affect behavior,
might the disruption of our gut microbiome,
our good gut bacteria,
be a potential factor in the causation of autism?
Where’d they get that idea from?
Well, kids with autism do tend
to have altered gut flora,
different than that of
children without autism,
for example, significantly less Prevotella
in autistic children, which, if you remember,
characterized the healthy gut enterotype
that you can foster the growth of
yourself with a more plant-based diet.
But, which came first?
Instead of the bad gut flora leading to autism,
isn’t it more likely that the autism
led to the bad gut flora?
Children with autism eat diets
with significantly fewer servings of fruits and vegetables,
often characterized by a lack of variety,
an inadequate amount of fiber-containing foods,
meaning whole plant foods in general,
and an increased amount of added sugars.
So, couldn’t that explain
the different gut flora right there?
There are some perinatal risk factors
for the development of autism,
including premature birth, low birth weight,
and delivery by caesarean section—
particularly the C-section.
What does that have to
do with the microbiome?
Well, there may be a protective value
offered by the maternal vaginal microbiome
that the infant misses out on
when they instead come out
through a surgical incision.
But, during a C-section,
the mothers are also sometimes
placed under general anesthesia,
and it’s possible that the anesthetics
could affect the baby's brain
before he or she is disconnected from the maternal blood supply.
To differentiate between the two scenarios,
we need a study that compared autism risk
between C-sections in which the mom
just got an epidural or spinal block,
versus C-sections under general anesthesia,
but there's never been such a study…
until now.
This study examined the incidence of autism
in infants delivered vaginally,
by C-section with just regional anesthesia,
and by C-section with general anesthesia.
And only those delivered by C-section
under general anesthesia had higher risk,
not those in C-sections where mom
just got like an epidural;
so, that would suggest the C-section connection
is more of an anesthesia
drug exposure thing
than involving the lack
of vaginal flora exposure.
This wasn't an interventional trial, though,
in which mothers were randomized into various groups,
just an observational study.
So, it’s possible the increased autism risk
has less to do with the anesthetic itself
than the pregnancy complications that may have led
to having to put the mother under.
Either way, I’m not seeing the microbiome connection.
They’ve tried probiotics for children with autism,
and so far, they don’t seem to have helped much.
Some families, in desperation, have tried fecal transplants
where they like beg the neighbor kid to donate.
It’s like what one fly said to the other—
is this stool taken?
Not FDA-approved, though;
so, families are forced to go on the brown market... (ahem).
It can all be traced back to this remarkable study
published in the Journal of Child Neurology.
Several parents of children
with regressive-onset autism—
meaning the kids started out acting
normally before the autism struck—
noted that it all seemed to start
after their child had taken antibiotics.
They had gotten chronic diarrhea
–autism isn’t the only thing that can run in your genes...(ahem)
suggesting the antibiotics had mucked
with their gut flora, and then came the loss
of language, play, and social skills.
Now, this could be a total coincidence,
but it led this group of pediatric gastroenterologists
to speculate that maybe there was
some sort of cause- and-effect link there.
Maybe by wiping out the good bugs,
some bad bugs took hold,
some neurotoxic bugs,
and that led to the autism.
If this were true, maybe they could
clean the slate once again,
another dose of antibiotics,
but this time to try to clear out
any bad bugs lurking down there.
Might that reduce autism
symptoms in these individuals?
That would be groundbreaking.
They put the kids on a powerful
antibiotic called vancomycin,
and 80% of the kids got better.
But, within a few weeks after the treatment,
most of them slipped back
towards their baseline,
suggesting that perhaps the bad bugs
got pushed down but not out.
This study was performed
nearly 20 years ago
and only had an “n” of 11,
meaning it only looked at 11 kids.
(The letter n is research-speak for
the number of subjects in a study).
Surely, by now, there’s been
lots of larger studies done.
But, in reality, there’s only been
a single follow-up study published,
and it had an n of 1.
A case report of a child with autism
improving on antibiotics and a father’s quest
to understand what it all may mean,
written by the father himself,
describing a dramatic improvement in the child’s autism
after taking amoxicillin.
When he talked to other parents of autistic children,
he was surprised to discover that many of them routinely
gave their children antibiotics expressly for that purpose,
though he also heard from other parents
that felt that their children’s autism
got worse after antibiotics,
or that antibiotics were blamed
for the emergence of the disorder in the first place.
But, that all speaks to the
potential role of the gut flora,
just reinforcing the notion.
Other parents were talking about it,
but then when he scoured the medical literature to learn more,
all he was able to turn up was that 11-child study.
How is it possible that there hadn’t been follow-up studies?
Here it was, right before his eyes,
personally witnessing evidence in his own child
what this study had shown, this seemingly intractable condition
rapidly and dramatically ameliorated
in response to an antibiotic— at least in some children,
but surprisingly there were no attempts
to repeat that study.
Now, I think most parents would probably
just count their blessings,
that at least it worked on their child and leave it at that,
but not this parent.
He started his own Autism Research Foundation,
with the mission of encouraging, sponsoring, and communicating
breakthrough autism research.