This post started with the post below on Facebook

I was curious if by chance some bacteria produced it. To find such information you must start with KEGG: Kyoto Encyclopedia of Genes and Genomes. On that site we find a description of the condition, we also find information about this enzyme glucose-6-phosphate dehydrogenase (NADP+) EC 1.1.1.49

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

1. Rotate bacteria inhibitors (antibiotics, herbs, probiotics) every 1-2 weeks
2. Some herbs/spices are compatible with probiotics (e.g., Wormwood with Bifidobacteria)
3. Verify dosages against reliable sources or research studies, not commercial product labels. This Dosages page may help.
4. There are 3 suppliers of probiotics that I prefer: Custom Probiotics , Maple Life Science™, Bulk Probiotics: see Probiotics post for why
5. 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)
• Potential underlying conditions (e.g., H-pylori, carbohydrate digestion issues)
• Individual susceptibility to specific probiotics
• Nature of symptoms (e.g., headache type – pressure, cluster, or migraine)
• Possible histamine issues
• Colon acidity levels
• SCFA production and acidification needs

A knowledgeable medical professional can help tailor recommendations to your specific health needs and conditions.

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

• Sulforaphane Treatment in Children with Autism: A Prospective Randomized Double-Blind Study.
• Therapeutic efficacy of sulforaphane in autism spectrum disorders and its association with gut microbiota: animal model and human longitudinal studies
• Current understanding and future directions of cruciferous vegetables and their phytochemicals to combat neurological diseases.
• Exploring sulforaphane as neurotherapeutic: targeting Nrf2-Keap & Nf-Kb pathway crosstalk in ASD.
• A Review on Autism Spectrum Disorder: Pathogenesis, Biomarkers, Pharmacological and Non-Pharmacological Interventions.
• Emerging drugs for the treatment of irritability associated with autism spectrum disorder.

Zinc

• Dietary zinc supplementation rescues fear-based learning and synaptic function in the Tbr1(+/-) mouse model of autism spectrum disorders.
• Potential importance of supplementation with zinc for autism spectrum disorder.
• The Assessment of Selenium, Aluminum, and Zinc in Children with Autism Spectrum Disorder.
• Differential effectiveness of dietary zinc supplementation with autism-related behaviours in Shank2 knockout mice.
• Zinc Water Prevents Autism-Like Behaviors in the BTBR Mice.
• xploring potential mechanisms for zinc deficiency to impact in autism spectrum disorder: a narrative review.
• Zinc deficiency and supplementation in autism spectrum disorder and Phelan-McDermid syndrome.
• Zinc Status and Autism Spectrum Disorder in Children and Adolescents: A Systematic Review.
• The association of vitamin A, zinc and copper levels with clinical symptoms in children with autism spectrum disorders in Jilin Province, China.
• Neurodevelopmental Consequences of Dietary Zinc Deficiency: A Status Report.
• The Role of Zinc and NMDA Receptors in Autism Spectrum Disorders.
• Zinc is a key regulator of gastrointestinal development, microbiota composition and inflammation with relevance for autism spectrum disorders.
• Impact of Zinc Oxide Nanoparticles on the Composition of Gut Microbiota in Healthy and Autism Spectrum Disorder Children.
• The role of zinc supplementation on the metallothionein system in children with autism spectrum disorder.
• In vitro zinc supplementation alters synaptic deficits caused by autism spectrum disorder-associated Shank2 point mutations in hippocampal neurons.
• Dietary Zinc Supplementation Prevents Autism Related Behaviors and Striatal Synaptic Dysfunction in Shank3 Exon 13-16 Mutant Mice.

and more studies…

Glyphosate

Studies from US National Library of Medicine

“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.

Impact of glyphosate (Roundup^TM) on the composition and functionality of the gut microbiome

• Is autism a PIN1 deficiency syndrome? A proposed etiological role for glyphosate.
• Maternal exposure of mice to glyphosate induces depression- and anxiety-like behavior in the offspring via alterations of the gut-brain axis.
• Autism-like Behaviors in Male Juvenile Offspring after Maternal Glyphosate Exposure.
• Pesticides used in Europe and autism spectrum disorder risk: can novel exposure hypotheses be formulated beyond organophosphates, organochlorines, pyrethroids and carbamates? – A systematic review.
• The relationship between pesticide exposure during critical neurodevelopment and autism spectrum disorder: A narrative review.
• Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase.
• Gut microbiota and neurological effects of glyphosate.
• Inflammatory state and autism-like behavioral phenotype of offspring induced by maternal exposure to low-dose chemical mixtures during pregnancy in mice.
• Clostridium Bacteria and Autism Spectrum Conditions: A Systematic Review and Hypothetical Contribution of Environmental Glyphosate Levels.
• Evidence the U.S. autism epidemic initiated by acetaminophen (Tylenol) is aggravated by oral antibiotic amoxicillin/clavulanate (Augmentin) and now exponentially by herbicide glyphosate (Roundup).
• Elevated Urinary Glyphosate and Clostridia Metabolites With Altered Dopamine Metabolism in Triplets With Autistic Spectrum Disorder or Suspected Seizure Disorder: A Case Study.

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.

• Current Studies for Brain Trauma
• Current Studies for Autism

Example Report

Example for a (real) person with Autism, OCD and Chronic Fatigue Syndrome

Bacteria Identification

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

• Google Sheets
• Excel Spread Sheet below:

Using the five methods described in Technical Note: The Four Winds of Microbiome Analysis, I ran these method on all of the data on the citizen science site of Microbiome Prescription testing for all symptoms that have been self-reported from users of Ombre Labs and Biomesight retail microbiome tests. The data from each lab was done is insolation (you cannot mix data from different processions flows, see The taxonomy nightmare before Christmas… for how the results from the same FASTQ files are reported by 4 different processing flows).

My criteria for deeming a genus significant was:

• At least one method reported P < 0.01
• At least two methods reported P < 0.05

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,

See Citizen Science Symptoms To Genus Special Studies

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.

Also see Technical Note: Yield of Applying Different Statistical Methods for more information

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.

Technical Methodology Details are described here Technical Note: Prevalence, Average and Not Reported.

Post-Script

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

• Case Study: Rapid Complete Recovery From An Autism Spectrum Disorder After Treatment of Aspergillus With The Antifungal Drugs Itraconazole And Sporanox [2020]
• Could Candida Overgrowth Be Involved in the Pathophysiology of Autism? [2022]
• Dysbiotic microbiota in autistic children and their mothers: persistence of fungal and bacterial wall-deficient L-form variants in blood [2019]
• Role of mycotoxins in the pathobiology of autism: A first evidence [2017]
• Mycotoxin Exposure and Autism: A Systematic Review of the Molecular Mechanism [2021]
• Effects of Mycotoxins on Neuropsychiatric Symptoms and Immune Processes [2018]
• New evidences on the altered gut microbiota in autism spectrum disorders [2017]
  “We also observed that the relative abundance of the fungal genus Candida was more than double in the autistic than neurotypical subjects,”
• See also: CDC provides a list of known fungal diseases: Types of Fungal Diseases.

Fungi are listed from lowest taxonomy level upwards.

• Fungi: Agaricales / Agaricomycetes – Eating button and baby bella before the test may result in a false high.
• Fungi: Aspergillus / Aspergillaceae / Eurotiales
• Fungi: Chaetomiaceae / Sordariales / Sordariomycetes
• Fungi: Clavicipitaceae / Hypocreales / Sordariomycetes
• Fungi: Debaryomycetaceae / Saccharomycetales / Saccharomycetes
• Fungi: Exophiala / Herpotrichiellaceae / Chaetothyriales – Loves Dishwashers!
• Fungi: Leotiomycetes / Ascomycota
• Fungi: Malassezia / Malasseziaceae / Malasseziales / Malasseziomycetes / Basidiomycota – associated with Inflammatory Bowel Disease and Crohn’s
• Fungi: Nectriaceae Fusarium / Hypocreales / Sordariomycetes – Loves garlic!
• Fungi: Pleosporales / Dothideomycetes
• Fungi: Saccharomycetaceae / Saccharomycetales / Saccharomycetes
• Fungi: Synchytrium / Synchytriaceae / Synchytriales / Chytridiomycetes / Chytridiomycota
• Fungi: Trichosporonaceae / Trichosporonales / Tremellomycetes / Basidiomycota

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.

Diagram from World Health Organization fungal priority pathogens list to guide research, development and public health action

Possible Medical Plants are covered in this article: A Review: Antifungal Potentials of Medicinal Plants [2015] . e.g. Garlic and other wonder herbs do not work on all fungi. 

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.

What we know about Autism Microbiome and Related issues – YouTube

The Excel File used above

What’s next?

Simple, develop a suggestion algorithm that is a superior match for this data than the default on Microbiome Prescription.

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.

Tax_Name	Tax_rank	Frequency seen in Autism	Frequency seen in Control	Frequency Chi2
Senegalimassilia	genus	28.9	13.8	31.7
Bifidobacterium pseudocatenulatum	species	17.9	7.3	29
Megamonas	genus	30.3	17.3	19.2
unclassified Clostridiales	family	46.3	30.1	17.4
Hungateiclostridiaceae	family	44.5	28.7	17.1
Abiotrophia	genus	14.7	7	16.4
Nitriliruptoria	class	17.4	33.3	15.6
Adlercreutzia equolifaciens	species	27.5	45.7	15
Euzebyaceae	family	17.4	32.8	14.9
Euzebyales	order	17.4	32.8	14.9
Euzebya	genus	17.4	32.8	14.9
Megamonas funiformis	species	15.6	7.8	14.8
Intestinibacter bartlettii	species	36.2	23.2	14.6
Adlercreutzia	genus	31.7	50.3	14.4
Euzebya tangerina	species	17.4	32.4	14.3
Brochothrix	genus	17.4	31.8	13.4
Olivibacter	genus	22.9	38.3	12.8
Pseudoclostridium	genus	27.1	43.4	12.7
Pseudoclostridium thermosuccinogenes	species	27.1	43.4	12.7
Eggerthella sinensis	species	15.1	28.4	12.7
Symbiobacteriaceae	family	25.2	40.9	12.5
Odoribacter denticanis	species	19.3	33.2	12.1
Brochothrix thermosphacta	species	17	30.3	12.1
Erysipelothrix muris	species	26.6	41.9	11.6
Hymenobacter	genus	20.2	33.8	11.4
Hymenobacteraceae	family	26.1	40.9	11.1
Dolichospermum	genus	20.2	33.6	11.1
Corynebacterium durum	species	17	9.6	11
Acidaminococcus fermentans	species	21.6	35.1	10.7
Selenomonas	genus	37.2	53.7	10.6
Aphanizomenonaceae	family	21.1	34.4	10.6
Bifidobacterium angulatum	species	17.4	10.1	10.5
Ruminiclostridium cellobioparum subsp. termitidis	subspecies	21.6	34.8	10.4
Carboxydocella ferrireducens	species	16.1	27.9	10.4
Ruminiclostridium cellobioparum	species	22.9	36.4	10.3
Dysgonomonas wimpennyi	species	26.6	40.9	10.3
Caldicellulosiruptor	genus	34.4	50.1	10.1
Clostridiales Family XVI. Incertae Sedis	family	18.8	31.1	10.1
Carboxydocella	genus	18.8	31.1	10.1
Senegalimassilia anaerobia	species	16.5	9.5	10
Streptococcus mutans	species	20.2	12.3	10
Pseudobutyrivibrio xylanivorans	species	33.9	49.3	9.9
Hathewaya histolytica	species	35.3	50.8	9.8
Hymenobacter xinjiangensis	species	14.7	25.7	9.7
Porphyromonas canis	species	21.1	33.6	9.6
Oscillospira	genus	45.9	62.9	9.6
Nostocaceae	family	29.8	44	9.4
Prevotella timonensis	species	22.5	35.1	9.3
Intestinibacter	genus	51.4	38.1	9.3
Butyrivibrio proteoclasticus	species	24.8	37.8	9.3
Propionispora hippei	species	21.1	33.3	9.2
Thermicanus	genus	42.7	58.8	9.1
Amoebophilaceae	family	31.7	45.8	9.1
Thermoclostridium caenicola	species	20.2	32	9
Oscillospira guilliermondii	species	31.2	45.2	9
Clostridium cellulovorans	species	15.6	9.1	8.9
Hungateiclostridium	genus	32.1	22.2	8.7
Blautia coccoides	species	37.2	51.8	8.6
Candidatus Amoebophilus asiaticus	species	31.7	45.4	8.5
Finegoldia magna	species	37.2	51.7	8.5
Bacteroides stercorirosoris	species	37.6	52.2	8.5
Amoebophilus	genus	31.7	45.4	8.5
Bifidobacterium catenulatum subsp. kashiwanohense	subspecies	30.3	20.8	8.5
Phascolarctobacterium succinatutens	species	36.2	50.6	8.4
Peptoniphilus methioninivorax	species	24.3	36.5	8.4
Planifilum fimeticola	species	21.1	32.6	8.3
Bifidobacterium catenulatum	species	31.7	22	8.3
Tindallia magadiensis	species	27.5	40.2	8.3
Anaerovibrio lipolyticus	species	31.7	45.1	8.3
Acholeplasma	genus	41.7	56.7	8.2
Hathewaya	genus	52.3	68.7	8.2
Thiothrix	genus	25.2	37.4	8.2
Propionispora	genus	24.3	36.2	8.1
Alkaliphilus crotonatoxidans	species	34.4	48.1	8.1
Pseudoramibacter	genus	14.2	23.9	8
Acidaminococcus	genus	40.8	55.1	7.7
Sphingobacterium bambusae	species	29.8	42.3	7.6
Thiotrichaceae	family	26.1	38	7.6
Anaerovibrio	genus	32.6	45.5	7.6
Bifidobacterium boum	species	24.8	16.7	7.6
Shewanella	genus	25.7	37.3	7.5
Shewanellaceae	family	25.7	37.3	7.5
Caulobacteraceae	family	18.3	28.5	7.4
Planifilum	genus	22	32.9	7.4
Rhodothermus	genus	33.9	46.9	7.4
Tetragenococcus doogicus	species	18.3	28.5	7.4
Bifidobacterium thermacidophilum	species	21.6	14.2	7.4
Sphingobacterium shayense	species	31.2	43.7	7.4
Caulobacterales	order	18.3	28.5	7.4
Selenomonas infelix	species	33.9	46.9	7.4
Oscillatoriaceae	family	17.4	27.2	7.3
Bilophila wadsworthia	species	45.4	59.9	7.3
Anaerostipes hadrus	species	50	38.4	7
Bacteroides faecis	species	38.5	51.8	7
Caloramator mitchellensis	species	36.7	49.4	6.7
Streptococcus fryi	species	18.8	28.4	6.7
Acetobacteraceae	family	17	26.1	6.5
Moorella group	norank	30.7	42.2	6.4
Chlorobaculum	genus	30.7	42.2	6.4
Butyricimonas virosa	species	28.4	39.5	6.4
Sphingobacterium	genus	39.9	52.4	6.2
Sedimentibacter	genus	43.1	56.1	6.2
Rhodothermus clarus	species	33.9	45.7	6.2
Sedimentibacter hydroxybenzoicus	species	38.5	50.9	6.2
Thiotrichales	order	36.2	48.3	6.2

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:

• A Systematic Investigation of Complement and Coagulation-Related Protein in Autism Spectrum Disorder Using Multiple Reaction Monitoring Technology [2023]
  • “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.”

• The use of data independent acquisition based proteomic analysis and machine learning to reveal potential biomarkers for autism spectrum disorder [2023]
  • “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, …”
• [Paired and partial correlations of immune parameters of neuro-immuno-test and coagulation parameters of thrombodynamics test in children with children’s autism] [2022]
  • “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).”
• Evaluation of Platelet Parameters in Children with Autism Spectrum Disorder: Elongated Collagen-Adenosine Diphosphate and Collagen-Epinephrine Closure Times [2019]
  • “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”
• [Thrombodynamic parameters of hypercoagulation of blood in children with childhood autism and schizophrenia] [2019]
  • “It was shown for the first time that clotting (hypercoagulability) of the blood plasma in patients with autism and childhood schizophrenia was increased. “
• [Thrombodynamic correlates of catatonia severity in children with autism] [2019]

Where do we go from here?

If you can get piracetam — it could be an experiment to try (800 mg with each meal for a few days).  see https://cfsremission.com/2021/04/20/piracetam-for-me-cfs-long-haul-covid-brain-fog-2/ . It works extremely well for me (but your mileage may vary)

For more items, see my old post in a different context for Thick Blood Supplements easily available.

Remember, systematic (one at a time) trials with (hopefully ) some way of objectively evaluating changes.

One possible way to evaluate, is to monitor Saturated O2 levels. There are [cheap] smart watches that will do that constantly.

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:

• blackcurrant – all 10
• low-fat diets – all 10
• red alga Laurencia tristicha – all 10
• lard – all 10
• Methionine – all 10
• fat – all 10
• glycyrrhizic acid (licorice) was 9 for and 1 against

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).

• cycloserine – D‐cycloserine for autism spectrum disorder [2019]
• Bumetanide – Bumetanide for autism: Open‐label trial in six children [2021]
• cefixime – Beta-Lactam Antibiotics as A Possible Novel Therapy for Managing Epilepsy and Autism, A Case Report and Review of Literature [2015]
• chlorpromazine hydrochloride – The Pharmacological Treatment of Autistic Spectrum Disorders [2014]

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)
  • Biotin, Vitamin B7
  • Arginine
  • Glutamine
  • N-Acetyl Cysteine (NAC),

Questions

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
  • 2023-08-21: 80% of the microbiome, 88%ile — Oscillospiraceae 89%ile,  Faecalibacterium prausnitzii 96%ile
  • 2022-07-11: 86% of the microbiome, 92%ile — Oscillospiraceae 94%ile,  Faecalibacterium prausnitzii 95%ile
  • 2021-11-29: 80% of the microbiome, 88%ile — Oscillospiraceae 79%ile,  Faecalibacterium prausnitzii 79%ile
  • 2020-10-14: 83% of the microbiome, 98%ile —  Oscillospiraceae 100%ile, Faecalibacterium prausnitzii 100%ile

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 Sequencing test 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.