More on Autism and the Microbiome…and a Clinical Study Using Probiotics

My Monday afternoon was devoted to reading two articles about the microbiome and autism.  The first was a chapter from a book on biological markers found in psychiatric and neurodegenerative disease.[i]  I’ve chosen what I thought were the top 10 points from this article to share with you:

1. It is 2019, and the authors still felt it necessary to state the following:  “Gastrointestinal problems that are seen associated with most of the autism cases suggest that it is not just a psychiatric disorder as many claim but has a physiological base, and alleviating the gastrointestinal problems could help in alleviating the symptoms by bringing out the much needed overall improvement in the affected victims.”  Ya think?  (I mean, isn’t this yet a given?!  All I could think about, as I read this, was the 7 year long battle I had, starting over 2 decades ago, to get a gastroenterologist to even see my son, let alone treat him.  The first 9 years of his life, his inflammatory bowel disease went undiagnosed and untreated.  Can you imagine that happening to anyone without an autism diagnosis?)

(I am going to step away from writing this to go beat my head against the wall for a bit.)

2. Autism “…stands out due to its prevalence and bewildering increase in epidemic levels throughout the world…”  Known physical illnesses also seen frequently in the autism population include, “…autoimmune reactions, food reactions, diagnostic connection of upper GI disease, abnormal stools, autistic enterocolitis [a distinct form of inflammatory bowel disease], leaky gut syndrome, excessive inflammation…”

3. The gut bacteria have a direct effect on the development of the sympathetic nervous system and thus, the host’s response to stress. Considering that anxiety and obsessive-compulsive disorder (which is a subset of anxiety disorders) is one of the most common symptoms found in the autism population, I thought this was worth noting.  Experiments on germ-free mice have shown that the animals have decreased anxiety…but a heightened stress response.  So while it may take more to get them stressed, when they are, they have an excessive response, and also have memory dysfunction. Further experiments have shown that the gut microbiota are very much responsible for setting the stress response point and modulate the serotonin system.
4. Remember too that the gut-brain axis works both ways. Two hours of social stress has been shown to cause alterations to the gut bacteria of mice, significantly reducing the proportions of a variety of species.  When animals have been subjected to postnatal stress (being separated from their mothers), there is a distinct reduction in Lactobacilli and disruption of the intestinal microbiota.  The animals were also “…more susceptible to opportunistic infection…”  (Just last week I wrote about a very recent study on stress and its affect on the microbiome.)
5. “Intestinal permeability is another grave issue faced by children with autism, suggesting a leaky gut which can lead to neurological disability as these children are forced to absorb neurotoxic molecules across a gut membrane damaged by inflammation. An abnormal level of intestinal permeability has also been documented in independently carried out studies.  A leaky gut allows molecules to enter the bloodstream, otherwise kept at bay.  Immune activation, tissue damage, and effects on the brain, including damage to brain tissue, are a few corollary problems that could emerge over time.”   (Read more about leaky gut here.)
6. Regarding the dysbiosis that has been established over and over to be present in people with autism: “The toxins that are produced by the harmful bacteria are not properly metabolized. They can build up in the brain by way of the bloodstream, resulting in confusion, delirium and even coma.  The GI inflammation and abnormal immune functions observed in children with autism may increase the abnormal levels of harmful bowel organisms, and metabolites produced by the harmful bacteria can create havoc intensifying GI inflammation, gut permeability, and abnormal immune functions.”
7. People with autism have fewer Bacteroidetes which play an important role in the digestion of polysaccharides (food (starches) and prebiotic fibers, that feed a healthy microbiome). In fact, at least one study has shown lower than normal levels of anti-inflammatory short-chain fatty acids in the population, which are produced by the digestion of polysaccharides.  I have written about impaired carbohydrate digestion and autism before.
8. As I have written about before, multiple studies have shown higher than normal levels of Clostridia. One of the metabolites produced by Clostridia species is HPHPA, which is “…thought to be responsible for depletion of catecholamines [certain neurotransmitters including dopamine, for example], and thus, it is believed to be a chief contributor in the exacerbation of typical autistic symptoms like stereotypical behavior, hyperactivity…”
9. The bacterial microbiome has been shown to alter the expression of genes responsible for “…limiting the heavy metal body burden,” and children with autism have been shown to have markedly higher levels of heavy metals than the neurotypical population.
10. Low levels of zinc have long been observed in the autism population. Optimal zinc levels have been shown to lead to an increase in bacterial diversity and increased levels of short chain fatty acids, while zinc deficient hosts have been shown to have GI microbiota in “pathological states.”

Not wanting to start my week on what really was a complete downer to read, I also read a fairly recent clinical study of probiotics in children with autism.[ii]  While this was an open-label study (i.e. the parents of the children knew they were giving their children probiotics), it was 3 months long…and it’s always good to see a study that is somewhat longer in duration.  It included 30 children with autism and 30 age-matched controls.  The children were given a probiotic (100 billion organisms) daily that was a mixture of Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacteria longum.  The results were quite dramatic actually:

1. At the start of the study, the children with autism had significantly lower levels of Bifidobacteria than the controls, but after the study, they found a significant increase in both Bifidobacteria and Lactobacillus.
2. The autism rating scale they used showed significant decrease in the severity of autism including in speech/language issues, sociability, sensory/cognitive awareness, etc.
3. There was significant improvement in GI symptoms.
4. There were no serious side effects and while 5 children had some mild symptoms (bloating, etc.), these were mild and transient, and no one dropped out of the study.
5. All their findings were consistent with previous clinical studies, including a 12 week long double blind, placebo-controlled probiotic study that was conducted in 2010 on 62 children with autism.
6. One final point, that I found interesting. “Sixty percent of autistic children in our study were overweight.  After probiotics supplementation for 3 months, these patients showed a statistically significant decrease in the body weight…”  This has, apparently, been shown before in previous probiotic studies.

I find myself yet again quoting the Harvard neurologist, Dr. Martha Herbert, who said – at a lecture I attended close to 20 years ago, “When faced with prolonged scientific uncertainty, use your best judgement.”

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[i] Pulikkan, J, Mazumder, A, Grace, T. Role of the Gut Microbiome in Autism Spectrum Disorders in Reviews on Biomarker Studies in Psychiatric and Neurogegenerative Disoers, Advances in Experimental Medicine and Biolgy, P.C. Guest (ed.). 2019;1118:253-269.  doi: 10.1007/978-3-030-05542-4_13.

[ii] Shaaban, SY, et. al. The role of probiotics in children with autism spectrum disorder: a prospective, open-label study. Nutritional Neuroscience. 2018;21(9):676-678.  doi: 10.1080/1028415X.2017.1347746