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.
Since it is deficiency, we look for an alternative supply from bacteria in the microbiome. There are many bacteria that has the capacity of producing it, but the enzyme may not be turned on (epigenetics). I was directed by perplexity to Wikipedia. This identifies a bacteria that is likely a high (actual) producer.
Leuconostoc mesenteroides: This bacterium has been shown to possess a G6PD enzyme that is reactive toward 4-hydroxynonenal, in addition to glucose-6-phosphate
This bacteria is available as a probiotic (one source).
General Information about Autism Enzymes and Compound Production
From the hundreds of donated microbiome samples annotated with Autism on Microbiome Prescription, I have done some statistical analysis (using a patent pending method for partitioning samples), “poor man metagenomics”, and have produce a summary on those who have an official diagnosis of autism.
First, I checked if EC 1.1.1.49 was on the list. It was not, which implies that is not a very common item across all autism patients.
Browsing the lists I did find two familiar items being high:
(R)-Lactate – also known as d-lactic acid, a common cause of brain fog and other neurological conditions see this for a list.
L-Histidine which is likely a protective feature (more information)
The amount of (R)-Lactate reported above was computed from the microbiome data which implies that reducing its level by microbiome manipulation is a viable path.
Modelling on an individual sample
With recent revisions of the UI, I have built an algorithm to select the probiotics that supply the maximum amount of these KEGG compounds and Enzymes that most meet the deficiencies detected.
To illustrate this feature, I took one of the autism samples upload and ask for the suggestions.
Below is the results of probiotics to increase the low KEGG compound in this sample.
Below is the results of probiotics to increase the low KEGG Enzymes in this sample. They are reasonably close to each other.
Bottom Line
This is all theoretical, but as probiotics are usually deemed to be safe and without significant risks, it is a possible experiment to try. Always take detail notes and report benefits and problems as comments on this post
It is interesting to note that the common Lactobacillus and Bifidobacterium are not need the top of either list.
An older video on the process
Postscript and Reminder
As a statistician with relevant degrees and professional memberships, I present data and statistical models for evaluation by medical professionals. I am not a licensed medical practitioner and must adhere to strict laws regarding the appearance of practicing medicine. My work focuses on academic models and scientific language, particularly statistics. I cannot provide direct medical advice or tell individuals what to take or avoid.My analyses aim to inform about items that statistically show better odds of improving the microbiome. All suggestions should be reviewed by a qualified medical professional before implementation. The information provided describes my logic and thinking and is not intended as personal medical advice. Always consult with your knowledgeable healthcare provider.
Implementation Strategies
Rotate bacteria inhibitors (antibiotics, herbs, probiotics) every 1-2 weeks
Some herbs/spices are compatible with probiotics (e.g., Wormwood with Bifidobacteria)
Verify dosages against reliable sources or research studies, not commercial product labels. This Dosages page may help.
My preferred provider for herbs etc is Maple Life Science™ – they are all organic, fresh, without fillers, and very reasonably priced.
Professional Medical Review Recommended
Individual health conditions may make some suggestions inappropriate. Mind Mood Microbes outlines some of what her consultation service considers: A comprehensive medical assessment should consider:
Terrain-related data
Signs of low stomach acid, pancreatic function, bile production, etc.
Detailed health history
Specific symptom characteristics (e.g., type and location of bloating)
I am doing a normalization and update of data on Microbiome Prescription. There are many items to review and items that have been reviewed have { } in their name. The pattern is:
Scientific Name
{Common Name}
Other Information
and not reviewed (YET)
So far in this review, I have come across two substances (more likely to come) where there has been many or interesting studies for Autism
Sulforaphane
This is found in broccoli sprouts,cauliflower, kale, cole crops, cabbage, collards, mustard, and cress
“Furthermore, it has been reported that most infant formulas are contaminated with glyphosate. One study reported levels between 0.03 mg kg−1 and 1.08 mg kg−1. This could potentially further exacerbate the problem of Bifidobacterium reduction in the infant gut.” This may be a factor for increasing Autism and ADHD rates.
I am working with a startup PrecisionBiome.eu and create a demo report exploring one of the features they want to consider on their pending offering. The draft feature used brain trauma as a test case. This caused me to think of Autism.
The draft report is designed to be a document to be used by Medical Doctors and to educate them on the latest studies.
All data contributed will be freely available for personal use on Microbiome Prescription, in keeping with its open data policy.
The person’s sample is examined and compared to the literature
Validated Suggestions
There are suggestions that the literature reports that some people in studies improved taking.
Not Validated Suggestions
These are items that will improved the microbiome but do not have any studies for them being tested with brain trauma / Autism. Conceptually, some researchers should conduct trials with them.
How Can You Help
We need to get a comprehensive list of items that help autism. This means YOU DOING RESEARCH, FILL OUT A SPREADSHEET and then send to me Ken@lassesen
The 2 @ P < 0.05 is a bit of shooting from the hip; I expect some correlation between methods but not sufficient to have that adjusted P value to be outside of the range 0.0025 and 0.01. Looking at the statistics on significant genus, we found the 2 @ P < 0.05 produce only a small contributions,
When I looked at associations for autism, I noticed a striking contrast between the two most common labs.
There are two possible causes:
Less annotated samples on Biomesight uploads
The algorithm being used on Biomesight is a poor match for the RNA used in 16s that are associated with autism (and other neurocognitive issues).
Looking at some other neurocognitive issues, we see the same pattern — Ombre identifies more significant genus.
How to Fix This Issue
The first issue may disappear if all biomesight samples with autism are annotated. HINT HINT
The second issue would be addressed by having the 16s FastQ files processed by OmbreLabs (At one time they offered that for free).
Example of Using
In the sample below, we see for Bifidobacterium that average amount is 2.6 x of the values of people without this symptom. The percentile rankings are 36% higher, and this genus is seen 3% more often.
Pending Work
Integrating this data with the algorithms on Microbiome Prescription to generate suggestions to reduce these shifts.
After I posted List of Bacteria significant for ME/CFS from the shared samples uploaded to Microbiome Prescription, several readers asked “How do I use this”. This person has a child with autism. This took me a few days to come up with, code and implement an answer.
I wanted this to go beyond just one condition because there is a huge variety of symptoms and co-morbidity seen with different conditions. After testing and tuning the algorithm, I am pleased with the current results.
The process is show below.
The Steps
Return to “My Profile”
A new button will appear
Clicking it will move to the page below. YOU MAY FIND THAT IT TAKES UP TO A MINUTE (We are doing a massive number of computation)
This will show a tree of the bacteria involved. The Species are under the genus they below to. In the example below we see the ENTIRE phylum that Bifidobacterium is in are low (none found) of 9 species whose presence would likely reduce your symptoms.
Elsewhere you may see highs with certain bacteria species desired to higher. Often the symptom key is at the species level.
At the bottom you will see a button to get suggestions
The next page shows the symptoms being targeted to and choices of what you want to consider.
Make any changes desired and click show suggestions
REMEMBER these are suggestions for ONE person using their Symptoms and their microbiome profile. It is intended for them only. Your own suggestions may be very different with many items exchanged between ADD and REMOVE.
This approach sidestep the proforma process often drilled into researchers (you must have a health control group and a verified, criteria matching target population) and keeps to rigorous statistical analysis while ignoring these constraints which are philosophical in nature. We used the available data and set our significance level to P < 0.005; instead of the typical research level of P < 0.05. In other words, we are 10 times more certain about our results.
This is intended to be used with reports from Thorne or Xenogene. A shotgun microbiome report is needed that reports Fungi. Most microbiome do not report fungi in detail.
Most microbiome reports use 16s technology that do not report on fungi. Fungi produces mycotoxins
CAUTION: Some test results may reflect foods (mushrooms) or supplements that you are consuming and could result in false high levels.
As a personal note, I am a high function autism; the first three years of my life I lived in an area known as “Asthma flats” and this early life exposure to high level of fungi may have been a factor for me.
This post presents solid evidence of items that are statistically significant based on 226 samples of people with Autism. The intent of this post is show the guns. Getting fingerprints and other “why” detective work is not included. This is just the statistical facts… painting a narrative is for others to do.
The following bacteria association with Autism is P < 0.01 or more significant. This is using the current 218 contributed samples.
When the Frequency seen is higher than Control, then there is too many. Additionally, the average amount seen in the list below is also higher than that seen in the Control. Same logic applies to those that are lower.
The probability of significance is using Chi2. A value of 6 is about P < 0.01, higher values are even more significant. As you will quickly note: Bifidobacterium for many species is too high.
I am a high functioning autistic person (which is a major factor in microbiome prescription being created — some autism characteristics allowed me to be super focused and not bored creating it), I know part of my issues was low grade coagulation issues — not usually deemed clinical significant usually. Coagulation impacts oxygen flow to the brain… which impacts behaviors. Hypoxia (low oxygen – i.e. from being at altitude without oxygen) have the following symptoms:
Euphoria
Headache
Increased response time
Impaired judgment
Drowsiness
Confusion or foggy decision making
And also speed of acquiring learning.
I did a little searching and found most of the items were very recent publications:
“The complement and coagulation pathways may be activated in the peripheral blood of children with ASD and play a key role in the pathogenesis of ASD.”
“45 differentially expressed proteins (DEPs) were identified between the ASD group and the control group. They mainly were associated with platelet degranulation, ECM proteoglycar, complement and coagulation cascades, selenium micronutrient network, …”
“It was shown that there is a statistically significant positive correlation (R=0.369, p=0.018) between the acquired immunity parameter: the level of serum antibodies to myelin basic protein (BMP): abBMP parameter, and the main parameter of platelet hemostasis – the time of appearance of spontaneous clots (Tsp).”
“Moreover, in terms of platelet functions, the elongation in collagen-ADP and collagen-EPI closure times were significantly higher for the ASD group (P = 0.044). These results may suggest an impairment in platelet functions rather than in platelet morphology for children with ASD. Considering these results, further investigation of thrombocyte functions in the ASD may lead to a better understanding of the pathogenesis of ASD”
“It was shown for the first time that clotting (hypercoagulability) of the blood plasma in patients with autism and childhood schizophrenia was increased. “
Autism is a variety of conditions caused by DNA mutations, environmental influences and a host of other factors. A significant contributor can be the microbiome. This impact can be further amplified because many children with autism are picky eaters shifting the microbiome further. What is discussed in this post applies to this child and not autistic children in general.
Back Story
A son with autism. He had COVID in April 2021. With autism, it can be challenging to identify long COVID symptoms from autism symptoms. “We have seen marginal improvements in his receptive language and command following. His social skills and emotional understanding is poor . His diet has largely remained the same , vegetables and chicken , lamb, beef or fish and spices. He is verbal but not conversational, does not sleep well at night, does stimming throughout the day, his understanding is minimal He has very good energy levels and is playing till he sleeps on most days. He has very good memory and learn preferred topics quickly but is unable to focus on any task , he is unable to write or hold pencil for long . He cannot always reply to questions and has ecolalia[unsolicited repetition of utterances made by others] . ”
Analysis
Lookin at Percentages of Percentiles, I see a different pattern than seen with ME/CFS and Long COVID — my most frequent analysis types. He has statistically (between 2 and 5%) significant abnormalities, but far less than people with ME/CFS and Long COVID.
Looking at Potential Medical Conditions Detected we see that ADHD and Mood Disorders patterns are there. Everything is reasonably in range for Dr. Jason Hawrelak Recommendations with two significantly out of range (too low) is Akkermansia (which is available as a probiotic) and Faecalibacterium prausnitzii is too high (27%). This pattern is seen across all of his samples.
Going over to our Citizen Science Special studies, the top three pattern matches are for:
COVID19 (Long Hauler)
Autism
Brain Fog
These also are seen with an earlier sample from 2020.
Plan for Suggestions
Since this is a persistent state with reasonable continuity across samples, I am going to go the Uber-Consensus route. By this I mean we will do for Each Sample:
“Just Give Me Suggestions” which executes 4 algorithms
Citizen Science using Autism
Then we combine the suggestions from each sample into one, an uber suggestion consensus. The advantage of this approach is to minimize minor fluctuations of the microbiome over time. This means that we have 20 sets of suggestions combined.
I was disappointed with the results — nothing was consistently suggested. I experimented and found that the last two samples gave more consistent results. This implies that there has been significant changes in the microbiome over the last two years.
The top suggestions from the PDF are below
As a FYI, in terms of how many times things were suggested:
I should talk a bit about the apparent contradiction with low-fat diets vs lard and fat. These come from the terms that clinical studies used. Low fat diet tends towards fish and poultry, lard is a pork product – I speculate that the type of fat may be significant.
On the flip side, we have these avoids. One item seems to be to suggest gluten free (despite wheat being a to-take):
As an experiment/learning activity — I looked at some of the suggested prescription items and checked if any are used for autism. We are matching these items impact on the microbiome and the shifts that this person has (autism as a diagnosis was not considered).
Since the non-prescription items above should cause similar shifts (and likely with less risk of side effects), it appears that the algorithms are making reasonable suggestions.
The process of checking suggestions derived exclusively from the microbiome against clinical studies for a condition is called cross-validation. When there is a high percentage of agreement, it implies that the mechanism may be via the microbiome and generating candidate substance from the microbiome may produce good results.
KEGG Based Suggestions
These use data from Kyoto Encyclopedia of Genes and Genomes to try to identify substances that the microbiome and the body may be short of which can be obtain via supplements or probiotics.
Probiotics (in decreasing priority)
Escherichia coli – which can be Mutaflor (recommended above) or Symbioflor-2 (which is easier for people in the US to get).
There were several items that are counter-indicated from the suggestions – when there is disagreement, don’t gamble — ignore
Akkermansia muciniphila – low positive score but also identify as low on Dr. Jason Hawrelak Recommendations
Supplements (again double checking across suggestions and keeping only that both agree with)
Q: His gut according to the test is in good condition. I have heard in the past from one of his doctors that his Gut results were one of the best that he has seen in Autistic children, but we have not been able to make a considerable shift in his symptoms in the last few years.
A: My working hypothesis is simple: symptoms are associated to microbiome shifts. He has bacteria shifts that are matches to autism drugs (see above); so I believe further improvement of the gut and behaviors are possible and probable. He may be good; I believe he can be better.
Q: Faecalibacterium prausnitzii is high in my son , I have read it works as anti-inflammatory , but on the contrary I have heard that children with ASD have an inflamed Brian ,I would have thought this would have worked in his favor.
A: Excellent question! Faecalibacterium prausnitzii is anti-inflammatory for Crohn’s disease[2008], colitis [2013]. I was unable to find any clear literature on its effect on the brain. I did found some information that cause me to suspect that it does not impact the brain significantly.
“A 15kDa protein with anti-inflammatory properties is produced by F. prausnitzii, a commensal bacterium involved in CD pathogenesis. This protein is able to inhibit the NF-κB pathway in intestinal epithelial cells and to prevent colitis in an animal model.” [2017] – the size of this is very important.
“Most proteins in the plasma are not able to cross the blood—brain barrier because of their size and hydrophilicity.” [Basic Neurochemistry]
“does not have a barrier against molecules less than 1 kDa.. may form a barrier against molecules larger than 4 kDa” [2020]
Bottom Line — it appears the chemical produced by Faecalibacterium prausnitzii may be too big to reach the brain.
We also find the following reported, suggesting we want to reduce it to a normal range, you should independently research this
“Faecalibacterium predicted social deficit scores in children with ASD” [2018]
“Faecalibacterium prausnitzii … were also found to be highly correlated with Autism Treatment Evaluation Checklist (a measure of Autism severity )”
On the flip side, it reduces abdominal pain and improved bowel movement in ASD [2018].
“Gut microbiome data revealed Akkermansia sp. and Faecalibacterium prausnitzii to be statistically lower in abundance in autistic children than their neurotypical peers with a five and two-fold decrease” [2021] — which may account for the gut issues.
“Compared with healthy controls, Faecalibacterium,..were more abundant in ASD patients” [2021]
Your son’s range is thus very atypical being many, many times higher than expected.
I have caution here, Faecalibacterium and cognitive issues have inconsistent reports [2021, 2023 ], Faecalibacterium is implicated in cognitive issues[2018]. IMHO, encouraging it to the normal ranges may be the wisest course.
Q: “His results are over all satisfactory ,same as last year about – Gut wellness score – 89.52. I have noticed that Clostridia is about 79.7 % could this be the reason, would appreciate your help.”
A: Clostridia has been high in most samples, I drilled down into it’s main components
Searching for Faecalibacterium + autism on PubMed resulted in 29+ studies. There was nothing found for Oscillospiraceae + autism. Looking at the latest sample, only 10% of the organisms in Oscillospiraceae could be identified in the sample — no smoking gun for which genus. Doing a Metagenomic Shotgun Sequencingtest would like provide more information (for example, Thorne) — but it is unlikely that will produce more actionable item — just give names.
Looking at what reduces Oscillospiraceae, we see Bumetanide, cycloserine, cefixime and chlorpromazine in that list (as well as many of the above suggestions).
Some visuals: Clostridia is not that extreme, but two of it’s children are.
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