Intent and Purpose

Be yourself; Everyone else is already taken.

— Oscar Wilde.

I am a high function ASD person in the late 60’s. I am a data scientist, artificial intelligence engineer, former high school science teacher etc. Needless to say, the term autism or ASD was unknown while I was growing up. The classic delay in speech (I did not start talking until I was almost 9 y.o.) and other characteristics were ascribed to some form of brain damage. Three causes were speculated: forceps delivery, German Measles at 18 months and the medication that my mother was give to keep from miscarrying (she had 6 miscarriages before me).

Today, I know that I was high risk because my father was 44 when I was born (Parental Age at Conception and the Relationship with Severity of Autism Symptoms. 2019). My childhood was not fun, because I understood enough about my situation that I was in terror for most of it. The terror caused me to work hard and I found success in a very non-social activity: mathematics and mathematics competitions. I placed in the top 3 repeatedly in both my Province and in Canadian Mathematics Competitions. That’s enough of my story.

Purpose of this Blog

Over the last few years I have became focused (the typical uber focus of an ASD person) on the microbiome to deal with family health issues. My primary focus has been on myalgic encephalomyelitis on which I have written some 1300 posts here. Out of that, I developed an analysis site using reference site and citizen science site called Microbiome Prescription. I have also became active in a Facebook group The Gut Club: Stool Test Discussion Group. This group had resulted in contact with many mothers with autistic children. Needless to say, I have both empathy for the mother and for the children (been there myself before there was support!).

This site is very open to guest posts. I do request that they be well researched with links to source studies. I hate to be ‘anti-social’ and ignoring chat-board opinions and consensus — but what do you expect from someone with ASD? 😉

As interesting notes comes across my desktop, I will explore and attempt to write up posts on what we know today.

I will start this blog by copying across some blog posts that I have done on Autism elsewhere.

ASD and Fecal Matter Transplants

FMTs have been tried for various conditions with mixed success. Autism has distinctive microbiome shifts and thus FMT should be consider as a treatment option. The why of failures has been an ongoing interest of mine. We may now have a significant factor that has been ignored in these attempts.

 Fecal microbiota transplantation (FMT) as a special organ transplant therapy, which can rebuild the intestinal flora, has raised the clinical concerns. It has been used in the refractory Clostridium difficile, inflammatory bowel disease, irritable bowel syndrome, chronic fatigue syndrome, and some non-intestinal diseases related to the metabolic disorders. But this method of treatment has not become a normal treatment, and many clinicians and patients can not accept it. 

[Research progress of fecal microbiota transplantation] 2015

This week’s Economist had an extended essay on Viruses and the like: The aliens among us/The Outsider within, this provides good background.

In addition to this, there was a podcast reporting success with FMT was associated with higher Phage Diversity in the donor. Phages are the police of the microbiome.

In this retrospective analysis, FMTs with increased bacteriophage α-diversity were more likely to successfully treat rCDI. In addition, the relative number of bacteriophage reads was lower in donations leading to a successful FMT. These results suggest that bacteriophage abundance may have some role in determining the relative success of FMT.

The success of fecal microbial transplantation in Clostridium difficile infection correlates with bacteriophage relative abundance in the donor: a retrospective cohort study (2019)

My earlier posts on FMT

Bottom Line

This implies that for a greater chance of success and less risk, than DYI fecal transfer, that a lab that tests for possible infections AND for phage state may yield the best results.

Suggestions by 2 different roads

I just pushed an update to the Special Condition Modifier page. You will see two links to suggestions on the page. See the earlier post here.

Suggestion are using published studies only
Suggestion are using machine learning from this site only

Pub Med

Citizen Science

Convergence!

There is a considerable one to one agreement with the suggestions. There is also agreement with gluten-free diet (i.e. no wheat, barley) which had positive results reported from studies (as well as B6).

In short, the microbiome analysis with suggestions appear to match actual studies — except we have more items suggested than been studied independently.

From the special condition page. Results from studies on PubMed

Implication for Specific Children

Above we are working from aggregations of many children with ASD. What is reported is not specific to one child. With an individual 16s stool sample test, then we can process that child’s unique individual microbiome profile thru and get suggestions specific for that child using the same logic as shown above.

The following 16s Providers provide data in an uploadable format. Biome Sight with “MICRO” as discount code and Thryve Alive

Low Oxygen in ASD Brains

This is usually called hypoperfusion ( Hypoperfusion is a term that describes “a reduced amount of blood flow”. ) and is seen in SPECT scans of the brain. I am experienced with it from episodes of ME/CFS relapse (SPECT scan reports) that had poor memory, poor decision making, easy mental fatigue, increased irritability during the relapse. It is my belief that metabolic changes induced by microbiome dysfunction was the cause of hypoperfusion.

There are some interesting similarities between CFS/ME and ASD, for example:

  • CFS/ME has increased Gray Brain Matter and decreased White Brain matter [2017]
  • ASD Has increased Gray Brain Matter [2006]

Literature on Autism and hypoperfusion

Treating Hypoperfusion

For ME/CFS, my treatment included sublingual heparin, piracetam and a variety of other items. Below are studies on various items that impacts hypoperfusion.

Possible Prescription Drugs

Low level coagulation as a contributor to hypoperfusion

For myself with ME/CFS, activation of coagulation was a significant factor and confirmed by labs tests from Hemex (this battery of tests is still available from one lab). Blood flow to the brain can be caused by:

  1. ‘thick blood'(think of a heavy oil(molasses) versus a light oil (water), one moves much slower than the other). Since blood delivers oxygen, it means less oxygen
  2. fibrin fibers (‘dirty filters’ that slows the slow, a blood clot would stop the flow)

What do we know from the literature on coagulation and autism?

Most of these issues are replicated in findings with ME/CFS (see links on this page: https://me-pedia.org/wiki/David_Berg).

There are many dimensions here, researched items that I have used include:

Bottom Line

In doing this post it was a bit of a surprise to see that 1st degree relatives was seen with similar conditions. For myself, it was not because I have an inherited coagulation defect (Prothrombin G20210A a.k.a. Factor II Mutation) so 1st degree relatives having it is to be expected.

The role of the microbiome and diet for hypoperfusion is not well explore. Emerging Role of Diet and Microbiota Interactions in Neuroinflammation [2018] gives an overview, but implications for hypoperfusion in autism is a to be determined.

This is an EDUCATIONAL POST, the items discussed above (including supplements) should be discussed with your medical professional before starting. This is not medical advice.

Lactic Acid Acidosis and Autism

Today I had a conversation with the parent of an autistic child. I have seen this pattern with other ASD children: High levels of lactobacillus and thus lactic acid production.

The test was done by Thryve, who bizarrely recommend Lactobacillus Probiotics….

Consequences of lactic acid production

I have had to deal with lactic acid acidosis with ME/CFS which often results in issues such as:

  • Slow memory processing speed
  • Poor memory
  • Poor executive decision / loss of focus

These are also reported with some autistic children. From the literature we see:

What can be done?

For more details see these older posts on my other blog.

Bottom Line

My suggestions (to be discussed with your medical professionals):

For a list of foods that decreases or increases Lactobacillus, go to the bottom of this page and type “food” in the filter. Click Effect until you get it in decreasing order.

N-AcetylCysteine (NAC) and Autism

NAC has a variety of impact on the microbiome, over 800 bacteria impacted. Predicted impact of NAC on the microbiome reported for Autism is that it will increase the shifts overall.

This post looks at reported studies (often these studies are very small samples which makes results unreliable).

Bottom Line

There are subjective reports of improvement that looked only at irritability and did not report on changes of other symptoms. The studies tend to focus on high irritability ASD.

Dosage from studies:  NAC (1200 mg/day). NAC has a half life of 6 hrs, so a dosage of 300 mg four times a day, or 400mg three time a day should be considered.

Autism and Oxytocin levels

Low levels of Oxytocin has been associated with autism. The impact of administration of Oxytocin is fuzzy.

Animal model research has documented that the administration of OXT and AVP was able to rescue autistic traits and increase social skills [119,120,121]. In humans, there is some evidence that the administration of oxytocin reduces some dysfunctional behaviors associated with autism, especially social skills, repetitive behaviors, anxiety, irritability, and self-injurious behaviors [122,123,124]. However, a recent meta-analysis that reviewed randomized controlled trials on ASD symptomatology did reveal that there was no benefit of oxytocin over placebo and provided further proof to support existing evidence [125].

The Neurochemistry of Autism , 2020

I know from other readings that extracts or refine products often are not as effective as the same chemical “au-natural”. The reason is that the au-natural version have additional chemicals that may work as a catalyst to improve the impact.

In keeping with this approach, I looked for ways of increasing it via the microbiome. This is what I found:

  • Oxytocin (OXT), as a neuropeptide, plays a role in emotional and social behaviors. Lactobacillus reuteri (L. reuteri) supplementation led to an OXT-dependent behavioral improvement in ASD mouse models [2020]

 It was previously shown that feeding of a human commensal microbe Lactobacillus reuteri (L. reuteri) is sufficient to up-regulate endogenous oxytocin levels and improve wound healing capacity in mice. Here we show that oral L. reuteri-induced skin wound repair benefits extend to human subjects. Further, dietary supplementation with a sterile lysate of this microbe alone is sufficient to boost systemic oxytocin levels and improve wound repair capacity. Oxytocin-producing cells were found to be increased in the caudal paraventricular nucleus [PVN] of the hypothalamus after feeding of a sterile lysed preparation of L. reuteri, coincident with lowered blood levels of stress hormone corticosterone and more rapid epidermal closure, in mouse models. 

Microbial Lysate Upregulates Host Oxytocin, 2016

I could not find studies for any other probiotics increasing oxytocin.

Summary

I checked Novel and Emerging Treatments for Autism Spectrum Disorders: A Systematic Review (2009) and found L. Reuteri was not listed, so this would be a newer suggestion.

  • Grade A treatments for ASD include melatonin, acetylcholinesterase inhibitors, naltrexone, and music therapy.
  • Grade B treatments include carnitine, tetrahydrobiopterin, vitamin C, alpha-2 adrenergic agonists, hyperbaric oxygen treatment, immunomodulation and anti-inflammatory treatments, oxytocin, and vision therapy.
  • Grade C treatments for ASD include carnosine, multivitamin/mineral complex, piracetam, polyunsaturated fatty acids, vitamin B6/magnesium, elimination diets, chelation, cyproheptadine, famotidine, glutamate antagonists, acupuncture, auditory integration training, massage, and neurofeedback.

It would be nice if someone did an update of these based on the last 11 years of research.

Gut Fungal and Autism

A reader passed me a link to an article published on May 23, 2020 which was very interesting.

Dysbiosis of Gut Fungal Microbiota in Children With Autism Spectrum Disorders, J Autism Dev Disorders , 2020 May 23. doi: 10.1007/s10803-020-04543-y. 

” Among the 507 genera identified, Saccharomyces and Aspergillus showed significant differences between ASD (59.07%) and Control (40.36%), indicating that they may be involved in the abnormal gut fungal community structure of ASD. When analyzed at the species level, a decreased abundance in Aspergillus versicolor was observed while Saccharomyces cerevisiae was increased in children with ASD relative to controls. “

The implication are simple:

  • Do not supplement with any Saccharomyces probiotics. Check carefully any probiotics that you use to insure there is none

I have been in recent discussion with a Ph.D. researching aspergillus oryzae because it frees up a lot of nutrients in food. There are over 3000 studies citing aspergillus, for example:

Production of GABA-enriched idli with ACE inhibitory and antioxidant properties using Aspergillus oryzae: the antihypertensive effects in spontaneously hypertensive rats.

A combination of acid lactase from Aspergillus oryzae and yogurt bacteria improves lactose digestion in lactose maldigesters synergistically: A randomized, controlled, double-blind cross-over trial.

Bottom Line

This is based on a report of a distinctive shift. Conceptually, Wakamoto would complete with Saccharomyces, reducing their numbers and altering the microbiome. There are no clinical studies done. Wakamoto is deemed safe and has been in use for a very long time in Japan.

Strong Wakamoto 1000 Tablets
This is available on Amazon US,Canada and Japan

Fecal Matter Transplants and Autism

This is a summary of studies on PubMed. Fecal Matter Transplants (FMT) works well permanently for some conditions, often just for a few months for other conditions, and rarely for other conditions. FMT does have risks to it. It is effectively an organ transplant and we are still learning about “compatible donors”. In a few cases, diseases may be passed; in rare cases deaths have been reported.

  • “Preliminary literature suggests that FMT may be a promising treatment option for several neurological disorders. However, available evidence is still scanty and some contrasting results were observed. A limited number of studies in humans have been performed or are ongoing, while for some disorders only animal experiments have been conducted. Large double-blinded randomized controlled trials are needed to further elucidate the effect of FMT in neurological disorders.” 2019
  • “An open-label study and a two-year follow-up suggest that MTT is relatively safe and effective in significantly reducing gastrointestinal disorders and autism symptoms, changing the gut microbiome structure, and increasing gut microbial diversity. Further research with larger, randomized, double-blind, placebo-controlled studies is warranted.” 2019
  • Microbiota Transfer Therapy (MTT) involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7-8 weeks. … clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. 2017
    • “we report on a follow-up with the same 18 participants two years after treatment was completed. Notably, most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment. ” [2019]

Bottom Line

  • Only a single reported study on 18 participants is in the literature.
  • Following the identical procedure is strongly recommended (often FMT is done as a “one shot” process, this extended doses for 8 weeks may be a very significant factor for it’s success)
  • Results were good on a subjective basis.
    • Technical issue: There was no control group used
  • Suggested donor would be a blood relative (ideally sibling) whose microbiome has been tested and show none of the shifts reported with autism which the target patient has.
  • [Speculation] Having the same blood type may contribute to higher success rate.

Factors associated with Autism

  • “Advanced parental age is a well-replicated risk factor for autism spectrum disorder (ASD),” [2020] Prefered both under 30.
  • “Advanced paternal or maternal age over 30 years was monotonically associated with increased ASD risk” [2020] ” ASD risk was higher among grandchildren of younger (≤19 years) grandparents” “Possible transmission of ASD risk across generations should be considered in etiological research on ASD.”
  • ” Risk factors for both disorders (ASD, ADHD) including maternal smoking, prematurity, and gestational diabetes” [2014]
  • “Extremely preterm children are at increased risk for autism spectrum symptoms and ASD in middle childhood.” [2010]
  • “In analyses where modeled prenatal maternal Per- and polyfluoroalkyl substances serum concentrations served as in utero exposure, we observed that prenatal  perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS)  exposure, but not other PFAS, were borderline associated with increased odds of child diagnosis of ASD” [2020]
    • “A single neonatal exposure to perfluorohexane sulfonate (PFHxS) affects the levels of important neuroproteins in the developing mouse brain” [2013] “These compounds are commonly used in products such as surfactant and protective coating due to their ability to repel water- and oil stains.”
    • “PFOS was the key ingredient in Scotchgard, a fabric protector made by 3M, and numerous stain repellents”
  • “Significant vitamin D deficiency is described within children affected by ASD and in pregnant mothers whose offspring will later develop ASD, suggesting a possible role of the hormone as a contributing risk factor in the etiopathogenesis of ASD. ” [2020]
  • “we concluded that there is consistent evidence supporting a positive association between early life inorganic Arsenic exposure and diagnosis of ASD ” [2019] see this article for where it is used (i.e. some pressure treated outdoor wood)
  • “Maternal occupational exposure to solvents may increase the risk for ASD. “[2019] – household cleaning solvents may be in scope.
  • “The observations that risk was highest for fall births (i.e., conceived in the winter) and lowest for spring births (i.e., conceived in the summer), and sunlight levels during critical neurodevelopmental periods explained much of the seasonal trends, are consistent with the hypothesis that a seasonally fluctuating risk factor may influence risk of ASD.” [2019]
  • ” Univariate analyses showed correlation for the presence of siblings with ASD, presence of family members with ASD, maternal use of medications and maternal smoking during pregnancy; and child’s gestational age at the start of prenatal vitamins with a diagnosis of ASD. ” [2019]
  • “Maternal history of eczema/psoriasis and asthma was associated with a 20%-40% increased odds of both ASD and DD.” [2019]
  • “Our data suggest that air pollutant exposure in early infancy but not during pregnancy increases the risk of being diagnosed with autism and Asperger among children” [2018]
  • “Potential prenatal causes suggested thus far are many and varied, including paracetamol [TYLENOL, Acetaminophen] (Archivist Oct 2016 doi.org/10.1136/archdischild-2016–3 11 708), antidepressant drugs (Archivist March 2016 doi.org/10.1136/archdischild-2016–3 10 462), ultrasound (Archivist Sept 2018 doi.org/10.1136/archdischild-2018–3 15 816), season of conception (Lucina Dec 2016 doi.org/10.1136/archdischild-2016–3 12 102), and obesity, among many others.[ BMJ 2019]
  • “These results support previous findings relating to sex and Science, Technology, Engineering and Mathematics (STEM) careers in the largest set of individuals for which  Autism-Spectrum Quotient scores..”[2015] In other words, a couple where both have a STEM career has a much higher odds of ASD off spring.
  • ” increasing risk of ASD (Kinney, Barch, Chayka, Napoleon, & Munir, 2010). These environmental factors could be mediated through pesticides (Roberts, Karr, & Council on Environmental Health, 2012), lead (Kim et al., 2013Parajuli, Fujiwara, Umezaki, & Watanabe, 2013Rahbar, White, Agboatwalla, Hozhabri, & Luby, 2002), arsenic (Parajuli et al., 2013Rahbar et al., 2012), mercury (Marques, Dorea, Bernardi, Bastos, & Malm, 2009Rahbar et al., 2013), or combustion pollutants (Tang et al., 2008). [highway/car pollutants] ” [2014]
    • “odds of having a child with ASD were twice as high for fathers who were engineers as compared to all other white-collar occupations’
    • ” fathers of cases were seven times more likely to work in healthcare “
    • “five times more likely to work in accounting/financial analysis”
    • “association of maternal occupations in healthcare with odds being twice as high in mothers of cases than controls”
    • “These results are consistent with the theories of Baron-Cohen (2006), who has also suggested that the combination of two highly systemizing parents may contribute to the likelihood of producing a child with ASD (Baron-Cohen, 2006Buchen, 2011), or in this case, a child with more recognizable symptomatology. “

Bottom Line

Time of conception plays an important role and age of parents. Delaying having a child increases the risk. Exposure to common household solvents, water-repellent material (Scotguard), and treated wood also increases the risk. Adequate Vitamin D may decrease the risk. A variety of over the counter and prescription drugs increases the risk (see this earlier post). Being in a clean rural environment during pregnancy and for the first years of a child life appears to be a definite positive.

Unfortunately couples form without evaluating the risk of two highly systemizing parents being involved.

Benfotiamine exploration

Benfotiamine is a dietary supplement that is a derivative of thiamine (AKA vitamin B1). From my CFS research, it may have benefits for autism.

Bottom Line

After reviewing with your physician, you may wish to consider supplementing, especially if there is aggression or more severe behaviors. See my ME/CFS post for dosages used.

The Beta-Amyloid aspect is interesting. I am a high function ASD who have had several rounds of ME/CFS (all triggered by stress, typically interpersonal). In one of these rounds, I had a SPECT scan. The radiologist read it as early Alzheimer’s. It is probable that he saw the build up of a pattern associated with beta-Amyloids. With recovery, the pattern disappeared.