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.
Statistics is fun because there many paths. Most studies using the microbiome uses the easy, but naïve, path of computing averages and standard deviation. As my dataset has grown, I have been travelling some less traveled path, for example: Visual Exploration of Odds Ratios, and a patent pending method termed “Kaltoft-Moltrup”.
One of the frequent decisions that I see in studies is to limit examination of bacteria that have a high frequency in the samples. This allows the researchers to keep to familiar and classic statistics. Using frequency of observation in the control group and the condition group is one of these much less travelled paths. It usually require big sample sizes and many studies have a sample size of 30 (sufficient for the mean and standard deviation approach).
I just completed code to compute Chi2 using Biomesight data for users reporting Autism.
Control Population: 3525
Autism: 88
Chi2 can be converted to probability (p) of happening at random with the following table
Seen too Rarely(Want to increase)
We see one bacteria available as a probiotic Bifidobacterium adolescentis. The rest would need to be altered by diet.
tax_name
TAX_RANK
Chi2
Observed
Expected
Shift
Butyricimonas synergistica
species
10
17
36
Under-Represented
Bifidobacterium adolescentis JCM 15918
strain
9.8
9
24
Under-Represented
Dehalobacterium
genus
9.7
18
37
Under-Represented
Pelotomaculum isophthalicicum
species
8
17
33
Under-Represented
Ammonifex thiophilus
species
7.3
17
32
Under-Represented
Seen too Often (Want to decrease)
We see 32 bacteria over a Chi2 of 6.635 ( P < 0.01 or 1 change in 100 of being a false detection). One very striking feature is that there are many, many different species of Bifidobacterium that are over represented while one species is under represented. This is not a simple situation to address.
tax_name
TAX_RANK
Chi2
Observed
Expected
Shift
Bifidobacterium catenulatum subsp. kashiwanohense
subspecies
43.5
54
23
Over-Represented
Bifidobacterium angulatum
species
33
39
16
Over-Represented
Staphylococcus pseudolugdunensis
species
23.6
20
7
Over-Represented
Clostridium cellulovorans
species
22.9
20
7
Over-Represented
Bifidobacterium catenulatum PV20-2
strain
19.5
58
33
Over-Represented
Streptococcus mutans
species
19
23
10
Over-Represented
Hungateiclostridium
genus
18.3
30
14
Over-Represented
Hungateiclostridiaceae
family
18.1
30
14
Over-Represented
Streptococcus intermedius
species
17.5
23
10
Over-Represented
Bifidobacterium catenulatum
species
16.9
58
34
Over-Represented
Absiella
genus
16.7
22
10
Over-Represented
Clostridium chartatabidum
species
16.7
43
23
Over-Represented
Bifidobacterium gallicum
species
15.4
73
47
Over-Represented
Prevotella veroralis
species
13
15
6
Over-Represented
Corynebacterium durum
species
12.6
14
6
Over-Represented
Bifidobacterium thermacidophilum
species
11.3
18
8
Over-Represented
Parascardovia
genus
10.5
32
18
Over-Represented
Klebsiella oxytoca
species
10.5
27
15
Over-Represented
Bifidobacterium scardovii
species
10
30
17
Over-Represented
Bifidobacterium cuniculi
species
9.9
31
18
Over-Represented
Candidatus Blochmanniella camponoti
species
9.8
21
11
Over-Represented
Abiotrophia
genus
9.2
12
5
Over-Represented
Enterococcus gilvus
species
9.1
14
6
Over-Represented
Megamonas funiformis
species
8.8
21
11
Over-Represented
Segatella oulorum
species
8.6
22
12
Over-Represented
Ralstonia
genus
7.9
14
7
Over-Represented
Bifidobacterium indicum
species
7.7
67
48
Over-Represented
Candidatus Blochmanniella
genus
7.2
35
22
Over-Represented
ant endosymbionts
clade
7.2
35
22
Over-Represented
unclassified Bacteroidetes Order II.
order
7.2
75
55
Over-Represented
Enterobacter hormaechei
species
6.9
36
23
Over-Represented
Moorella group
norank
6.7
66
48
Over-Represented
Bottom Line
The next step is to compute similar tables for all symptoms and incorporate these findings into a new algorithm. I say new, because I do not know if it is better than the existing ones. Conceptually, it would be added as a 5th set of suggestions to the existing consensus view on Microbiome Prescription.
This is a preview of the next generation of analysis. I described a mathematical model in Microbiome Guilds, Metabolites and Enzymes. I mentioned a concept in it and over the weekend tried the concept out. It worked and is very sweet.
To explain it, look at the chart below. The blue line is for those that have a symptom and the orange line is what is expected. If you divide observed by expected for different percentiles, you get an odds ratio. Most people know odds ratio (OR) from things like:
For current male smokers consuming >30 cigarettes daily:
This pattern does not determine that you will absolutely get it. It means that your are more likely — odds. (My native environment as a statistican)
This means that we move from a vague hand-waving “Too high” or “Too Low” to actual numbers (percentiles to be precise, not percentages).
Biomesight Bacteria
The genus bacteria listed below, each have at least an odds ratio of 1.5 for general fatigue using Biomesight data if your percentile is below the amount show. I stopped listing at 10%ile items. Compared to my earlier post for Bacteria Associated with General Fatigue, we have some really string candidates – 90!. 96 means 96%ile.
If you have 10 of them then 1.5 ^ 10 = 57x greater odds of having general fatigue. It is NOT one bacteria causing it, or even a specific group of bacteria, but different combinations of possible bacteria.
I should mention that these numbers only applies to Biomesight data. “results from one pipeline cannot be safely applied to another“. For background see: The taxonomy nightmare before Christmas.
. It potentially allows a screening test to be done for autism from a microbiome sample (and also hints at what specifically needs to be corrected).
Chlorobaculum >= 96
Roseococcus >= 94.9
Marichromatium >= 93.8
Ectothiorhodospira >= 93.8
Aquimonas >= 93.5
Xenophilus >= 92.5
Neorickettsia >= 90.9
Syntrophobacter >= 90
Pelomonas >= 88.5
Trichococcus >= 88
Steroidobacter >= 86.5
Desulfofrigus >= 65
Hathewaya <= 47.6
Pseudoclostridium <= 42.2
Desulfovibrio <= 37.9
Anaerovibrio <= 37.1
Ehrlichia <= 36.1
Phocaeicola <= 36
Johnsonella <= 30
Acetobacterium <= 27.6
Candidatus Amoebophilus <= 27.2
Oscillospira <= 25.2
Anaerotruncus <= 25.1
Erysipelothrix <= 24.9
Bacteroides <= 24.6
Porphyromonas <= 21.2
Selenomonas <= 21
Pedobacter <= 20.1
Ombre Equivalent Bacteria
If you have Ombre’s microbiome results, these are the critical bacteria. It is a much smaller list then above (and as expected, very few bacteria names in common — “the nightmare”)
Cystobacter >= 95.8
Cellulomonas >= 95.2
Tannerella <= 39.6
Erysipelatoclostridium <= 34.7
Alistipes <= 29.1
Alloprevotella <= 28.8
Phocaeicola <= 28.6
Oleidesulfovibrio <= 27.6
Pseudoflavonifractor <= 27.5
Odoribacter <= 25.6
Ethanoligenens <= 24.9
Pedobacter <= 24.3
Leyella <= 23.8
uBiome Equivalent Bacteria
There was not sufficient data to compute bacteria odds ration
Metabolites
I did a follow up post using Odds Ratio with Metabolites in the context of ME/CFS.
Metabolite-Centric Analysis
Bacterial Metabolic Activity: Bacteria produce and consume various metabolites, which can significantly impact the host’s metabolic environment13.Metabolic Imbalances: Different bacterial compositions can lead to similar metabolite imbalances, making metabolite profiles potentially more informative than bacterial species profiles alone7 8.
Advantages of This Approach
Net Effect: By examining metabolites, we can assess the overall impact of the microbiome on the host, regardless of the specific bacterial species present5.
Consistency: Metabolite imbalances may be more consistent across patients than bacterial species composition, which can vary widely7.
Functional Insight: This approach provides insight into the functional consequences of microbiome dysbiosis in ME/CFS3 8.
Understanding metabolite profiles in ME/CFS could lead to:
Improved diagnostic tools
Identification of potential therapeutic targets
Personalized treatment approaches based on individual metabolic profiles58
I am showing the numbers for Biomesight sample below. Conclusions across Ombre, uBiome and Biomesight are at the bottom.
Warning: These are the chemical names — a few are available as supplements with more common name.
Looking for Metabolites shared between Ombre and Biomesight samples, only a single metabolite was flagged by both for low: Hydroquinone (1.6%ile for Ombre, 26%ile for Biomesight).
Ombre flagged some 510 metabolites, while Biomesight flagged 542 metabolites. Too much to drill down into. So let us look at the shared one above in more detail.
Based on the Perplexity search results, hydroquinone has shown some interesting connections to cognitive functions, particularly in the context of brain injury and neuroprotection:
Neuroprotective Effects
Hydroquinone (HQ) has demonstrated significant neuroprotective properties in experimental models of brain injury:
In a rat model of transient focal cerebral ischemia, HQ treatment strongly alleviated ischemic brain injury3 4.
The neuroprotective effect of HQ was associated with the prevention of blood-brain barrier (BBB) disruption3. This is crucial because the BBB plays a vital role in maintaining brain homeostasis and protecting cognitive functions.
HQ treatment maintained the expression of tight junction proteins in the ischemic cortex, which are essential for BBB integrity3.
Potential Cognitive Benefits
While not directly tested for cognitive enhancement, the neuroprotective effects of HQ suggest potential cognitive benefits:
By preventing BBB disruption, HQ may help maintain normal brain function and protect against cognitive decline associated with ischemic events3.
Both pre- and post-treatment with HQ showed protective effects against ischemic damage in experimental models6. This suggests potential applications in both preventive and therapeutic contexts for cognitive protection.
Considerations and Limitations
It’s important to note some limitations and considerations:
Most studies on HQ’s neuroprotective effects have been conducted in animal models, and more research is needed to confirm these effects in humans3 4.
The typical use of HQ as a skin-lightening agent is unrelated to its potential cognitive effects5. Its primary application remains in dermatology.
High doses or long-term use of HQ may have adverse effects. A study on percutaneous drug delivery showed that high doses of HQ could impair hippocampal structure and induce behavioral disorders in mice1.
In conclusion, while hydroquinone shows promising neuroprotective effects that could potentially benefit cognitive functions, especially in the context of brain injury, more research is needed to fully understand its impact on human cognition and to determine safe and effective applications beyond its current use in dermatology.
Bottom Line
Adding this to the website to allow individual analysis of individual microbiome is high on my backlog. One of the benefits is the ability to focus on specific bacteria being at specific levels which conceptually should result in better suggestions.
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.
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