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.

Microbiome Prescription uses over a million rules to generate suggestions on improving the microbiome and hopefully reduce or moderate autism behavior. All of the sources of the rules are studies on the US National Library of Medicine. Microbiome Prescription also can provide the complete evidence trail for every suggestion! That is, where — precisely– is all of the information coming from — none of it is private personal opinion or speculation.

Cross Validation

Cross validation is the process of taking one set of information to generate forecasts or suggestions and then look at a totally independent source of information to see if the forecasts and suggestions are valid, reasonable, and appear to help individuals with the condition. I have done that for several conditions with very good results. NOTE: Everything is generated by code — code that I prefer to improve or correct. I have no personal stake in the suggestion, nothing to defend.

Source of Suggestions

Simple, 🥣 Candidates which is based on bacteria shifts reported from studies for autism: 🦠 Taxons. These two links are on the Medical Conditions with Microbiome Shifts from US National Library of Medicine page

The process is simple: some items may have been tests in trials for autism, some have not. If it has been tried, we see what the result in and provide a link to the study (open data!! no “trust me, I am an expert” hype)

• #1 bacillus subtilis (probiotics)  – it’s genetics may counter one DNA mutations in autism.
  • Two novel mutant human adenylosuccinate lyases (ASLs) associated with autism and characterization of the equivalent mutant Bacillus subtilis ASL [2004]
  • “Binding studies show that both the B. subtilis and human ASLs bind up to 4 mol of APBADP per mole of enzyme tetramer and that both enzymes exhibit cooperativity: negative for B. subtilis ASL and positive for human ASL.” [2008]
• #2 bifidobacterium longum (probiotics)  
  • Bifidobacterium longum CCFM1077 Ameliorated Neurotransmitter Disorder and Neuroinflammation Closely Linked to Regulation in the Kynurenine Pathway of Autistic-like Rats [2022]
  • Different Alterations in Gut Microbiota between Bifidobacterium longum and Fecal Microbiota Transplantation Treatments in Propionic Acid Rat Model of Autism [2022]
• #3 Wheat Bran — no pubmed studies
  • Cited positively for autism on Foods that Feed the Brain and Improve Behavior
  • Note: Gluten Free for autism is much debated in current literature with some advocating that it actually does harm for some. See Dietary Intake, Nutritional Status and Sensory Profile in Children with Autism Spectrum Disorder and Typical Development [2022]
• #4 bacillus licheniformis – no information
• #5 lactobacillus rhamnosus gg (probiotics) 
  • Effect of probiotic supplementation on cognitive function in children and adolescents: a systematic review of randomised trials [2019] “one study found a positive result with Lactobacillus rhamnosus GG (LGG) 1×10¹⁰ cfu supplementation with outcomes on attention deficit hyperactivity disorder (ADHD) or Asperger syndrome (AS) manifestations as diagnosed using the International Classification of Diseases-10 criteria. “
• #6 almonds/ almond skins – no information
• #7 apple   – no impact, but ” The most commonly consumed foods were tomato, carrot, banana, apple, ” [Nutritional status and food intake frequency in children with autism spectrum disorder] [2023] – which implies some positive effects seen by parents
• #8 lactobacillus casei (probiotics)  
  • Unexpected improvement in core autism spectrum disorder symptoms after long-term treatment with probiotics [2016]
• #9 fish oil
  • Dietary fish oil improves autistic behaviors and gut homeostasis by altering the gut microbial composition in a mouse model of fragile X syndrome [2023]
  • Effects of Omega-3-6-9 fatty acid supplementation on behavior and sleep in preterm toddlers with autism symptomatology: Secondary analysis of a randomized clinical trial. [2022]
• #10 sarcodiotheca gaudichaudii (red sea weed)  – no information
• #11 fasting  
  • Intermittent fasting uncovers and rescues cognitive phenotypes in PTEN neuronal haploinsufficient mice [2018] – “Pten mutations have a strong link with autism spectrum disorder.”
  • The Effects of Intermittent Fasting on Brain and Cognitive Function [2021] – Proposal for future studies
• #12 broccoli  
  • Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder [2021] “Sulforaphane (SF), an isothiocyanate from broccoli, is a multifunctional phytochemical that has several demonstrated benefits on cellular processes relevant to ASD, including cytoprotective, antioxidant and anti-inflammatory responses, mitochondrial and synaptic function, neuroinflammation and neuroprotective mechanisms, as previously reviewed”
  • Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli. [2018]
• #13 lactobacillus acidophilus 
  • The Effects of Probiotics and Prebiotics on Gastrointestinal and Behavioural Symptoms in Autism Spectrum Disorder. [2022]
  • Daily intake of Lactobacillus alleviates autistic-like behaviors by ameliorating the 5-hydroxytryptamine metabolic disorder in VPA-treated rats during weaning and sexual maturation. [2021]
• #14 lactobacillus paracasei (probiotics)
  • Unexpected improvement in core autism spectrum disorder symptoms after long-term treatment with probiotics [2016]
  • Emerging Role and Place of Probiotics in the Management of Pediatric Neurodevelopmental Disorders [2022]
• #15 purple sweet potatoes  –
  • Purple sweet potato color ameliorates cognition deficits and attenuates oxidative damage and inflammation in aging mouse brain induced by d-galactose [2009]
• #16 lactose  — Questionable for a subset
  • Genetic predictors of celiac disease, lactose intolerance, and vitamin D function and presence of peptide morphins in urine of children with neurodevelopmental disorders [2019]
  • Intestinal disaccharidase activity in patients with autism: effect of age, gender, and intestinal inflammation [2011] ” Lactase deficiency not associated with intestinal inflammation or injury is common in autistic children and may contribute to abdominal discomfort, pain and observed aberrant behavior. Most autistic children with lactose intolerance are not identified by clinical history.”
• #17 resistant maltodextrin  – no information
• #18 chondrus crispus (red sea weed)   – no information
• #19 Conjugated Linoleic Acid 
  • Conjugated Linoleic Acid and Brain Metabolism: A Possible Anti-Neuroinflammatory Role Mediated by PPARα Activation [2021]
• #20 green tea  
  • Amelioration of behavioral aberrations and oxidative markers by green tea extract in valproate induced autism in animals [2011]
  • The green tea polyphenol epigallocatechin-3-gallate (EGCG) restores CDKL5-dependent synaptic defects in vitro and in vivo [2020] “CDKL5 deficiency disorder (CDD) is a rare X-linked neurodevelopmental disorder that is characterised by early-onset seizures, intellectual disability, gross motor impairment, and autistic-like features. “

Score?

• Five items with no information
• Two items with weak information (not PubMed)
• Twelve items with confirmed information (PubMed)
• One item that is complex/questionable – depends on the child’s DNA

The goal / objective of Microbiome Prescription is to make suggestions that are more likely to help than to hurt. That goal seems to be accompanied. A secondary goal is to suggest items that have not been studied but modelling suggests that it may be of benefit to try. We have 5 such items above.

Remember these are GENERIC Suggestions for GENERIC Autism

The results of an individuals microbiome will be different — there are many variants and subsets for Autism. Each variant will tend towards their own set of variations for the microbiome. Using an individual’s microbiome sample will get suggestions unique for them.

Postscript – and Reminder

I am not a licensed medical professional and there are strict laws where I live about “appearing to practice medicine”.  I am safe when it is “academic models” and I keep to the language of science, especially statistics. I am not safe when the explanations have possible overtones of advising a patient instead of presenting data to be evaluated by a medical professional before implementing.

I cannot tell people what they should take or not take. I can inform people items that have better odds of improving their microbiome as a results on numeric calculations. I am a trained experienced statistician with appropriate degrees and professional memberships. All suggestions should be reviewed by your medical professional before starting.

The answers above describe my logic and thinking and is not intended to give advice to this person or any one. Always review with your knowledgeable medical professional.

A good starting point is: Interconnection between Microbiota-Gut-Brain Axis and Autism Spectrum Disorder Comparing Therapeutic Options: A Scoping Review [2023] a few quotes (worth reading the whole thing!)

 Kang and colleagues created a modified FMT procedure called MTT for autistic youngsters [29]. This therapy alleviated ASD behavioral symptoms to some extent, with excellent tolerance indicated and improvements lasting 2 years after treatment ceased….Fascinatingly, microbial metabolic genes for folate biosynthesis, oxidative stress defense, and sulfur metabolism were dissimilar from those found in normally developing (TD) patients at ASD baseline but mirrored those found in TD and/or donors following MTT [56].

Several investigations in recent years have indicated qualitative and quantitative changes in the gut flora in a variety of neuropsychiatric illnesses, supporting the role of Gut Microbiome (GM) in the maintenance of physiological condition in the CNS. Within neurobehavioral disorders, it appears that at least a portion of ASD instances are linked to, and maybe reliant on, the health and wellbeing of the GM.

Related FMT Studies:

• Efficacy of Fecal Microbiota Transplant on Behavioral and Gastrointestinal Symptoms in Pediatric Autism: A Systematic Review. [2023]
• Effect of fecal microbiota transplantation in children with autism spectrum disorder: A systematic review. [2023]
• Fecal Microbiota Transplantation in Autism Spectrum Disorder. [2022]
• Shotgun Metagenomics Study Suggests Alteration in Sulfur Metabolism and Oxidative Stress in Children with Autism and Improvement after Microbiota Transfer Therapy. [2022]

Caution: FMT can be tricky — determine the appropriate FMT sample to use is still being investigated. The donor microbiome should exhibits none of the shifts documented below, ideally the opposite direction.

Other Recent Studies

• Dietary fish oil improves autistic behaviors and gut hoeostasis by altering the gut microbial composition in a mouse model of fragile X syndrome. [2023]
  • This is cited as positive on our A Priori suggestions for the bacteria below.
• Lactobacillus reuteri normalizes altered fear memory in male Cntnap4 knockout mice. [2022]
  • This is cited as positive on our A Priori suggestions for the bacteria below.

Reported Shifts

Based on the literature cited here. We find the most frequently reported listed below. Note that Lactobacillus is high 8 times and low 5 times. My usual attitude when there are such contrary results is to ignore this species entirely.

This leads to the following probiotic suggestions:

• Do not use Lactobacillus — it is unclear if it will help or hurt
• Supplement with Bifidobacterium probiotics and items that support the growth of this bacteria
  • bifidobacterium longum (probiotics)  is the species that seems to be best in general
    Bifidobacterium longum CCFM1077 Ameliorated Neurotransmitter Disorder and Neuroinflammation Closely Linked to Regulation in the Kynurenine Pathway of Autistic-like Rats. [2022]
    Different Alterations in Gut Microbiota between Bifidobacterium longum and Fecal Microbiota Transplantation Treatments in Propionic Acid Rat Model of Autism. [2022]

• Supplement with Akkermansia muciniphila probiotics
• Supplement with Veillonella probiotics when it becomes available.

Tax_Name	Direction L – Low H – High	Studies
Bifidobacterium	L	13
Lactobacillus	H	8
Coprococcus	L	7
Prevotella	L	7
Streptococcus	L	6
Veillonella	L	6
Dialister	L	6
Bacteroides	L	5
Lactobacillus	L	5
Parabacteroides	L	5
Sutterella	H	5
Clostridium	H	5
Candida	H	4
Clostridium perfringens	H	4
Collinsella	H	4
Desulfovibrio	H	4
Sarcina	H	4
Megamonas	H	4
Fusobacterium	H	4
Lachnospiraceae	L	4
Veillonellaceae	L	4
Bilophila	L	4
Blautia	L	4
Akkermansia Muciniphila	L	3

Using Microbiome Prescription

For getting a microbiome sample, it is suggested that Thorne be used because it reports Clostridium perfringens levels in almost every sample. Ombre and Biomesight only report finding it between 11–16% of the time.

Then use this to generate suggestions specific for the autism associated bacteria shifts.

Next Post — Cross Validation

Cross Validation means checking the a priori suggestions (based on above bacteria shifts) against the literature to see if they agree. Three examples are above where studies and suggestions are in agreement.

I am planning to update my knowledge of Autism by reviewing recent literature. Taking different scopes in each set.

Before birth factors

• Prenatal exposure to per- and polyfluoroalkyl substances increases risk [2021]
  • “People are most likely exposed to these chemicals by consuming PFAS-contaminated water or food, using products made with PFAS, or breathing air containing PFAS.” [National Institute of Health]
  • “High maternal exposure to PFAS was consistently associated with increased abundance of Methanobrevibacter smithii in maternal stool. ” with some association to the infant microbiome. [2023]
• “Valproic acid (VPA) was reported to increase the prevalence of ASD in humans as a consequence of its use during pregnancy. ” [2020] [2017]
• “Maternal prenatal antifungal use and frequent prenatal antibiotic use are associated with an increased risk of ADHD in offspring” [2023] [2023] [2021] [2019]
• “Children of mothers with hypertensive disorders of pregnancy (HDP) have high rates of preterm-birth (gestational age < 37 weeks) and small-for-gestational-age (SGA), both of which are risk factors of autism spectrum disorder (ASD). ” [2023]
• “maternal prenatal exposure to lithium from naturally occurring drinking water sources in Denmark was associated with an increased ASD risk in the offspring.” [2023] [2023]
• “We found the previously reported relationship between precipitation and autism in a county was dependent on the amount of drinking water derived from surface sources in the county.” [2012]
  • Comment: PFAS etc. is more likely to be present in surface sources
• In animal studies:
  • Arsenic [2020]
  • Glyphosate [2021] – a widely used herbicide, “Roundup”
  • Environmental Pollutants [2015]
  • Water chlorination byproducts [2011]

After birth – early factors

• How was the infant fed? [2023], [2021] [2023]
  • Exclusive breastfeeding had lowest incidence
  • Partial breastfeeding had medium incidence
  • Exclusive formula feeding had highest incidence
• “women who gave birth by caesarean delivery were more likely to stop exclusive breastfeeding in the first 4 months, and those children who were not exclusively breastfed at 4 months were more likely to have autism-like behaviours “[2022]
• “Children with ASD have a shorter duration of breastfeeding, a later introduction of complementary foods, and poorer acceptance of complementary foods than typical children…The research suggests that continued breastfeeding for longer than 12 months may be beneficial in reducing ASD symptoms” [2023]
• “Difficulties during breastfeeding, breast milk refusal and avoidance of taking solids have been linked to ASD. Infants with ASD have been referred to as picky eaters. Problematic mealtime behaviour during infancy has also been associated with ASD.” [2022]
• “Constipation in early childhood was correlated with a significantly increased risk of ASD.” [2023]
• “Compared with children who did not use antibiotics during the first year of life, those who received antibiotics had a reduced risk of ASD ” [2018]
  • Comment: Could the antibiotics inhibit microbiome shifts contributing to autism?

As a FYI, I have taught Artificial Intelligence for Chapman University, worked as a AI/Software developer for Amazon and Microsoft. Artificial Intelligence is composed of a large number of very different techniques, at one end you have “ponies” and at the other end “Space Shuttles”. One technique, expert system with fuzzy logic (ESFL), appears to be the best. Why? Most of the techniques require vast quantity of training data and usually produce black box suggestions/predictions which lacks explanations of why. ESFL provides a complete logic/evidence trail for each suggestions/predictions which can be walked. If one piece of evidence is disputed, it can be removed easily and a new set of suggestions/predictions produced.

Build our own AI Autism Model?

This post comes from the success of using AI on Microbiome Prescription. It would be nice to see if we can do the same with Autism. The goal is to use all available knowledge from studies.

I would suggest using SWI-PROLOG as the main engine. Prolog is a language that does not compute numbers but compute logic. The following is actual program code. It is almost english-like and prolog can resolved what you should take or not take.

• increases(Modifier_A,Bacteria_31979).
• decreases(Modifier_X,Bacteria_1236).
• low(“person”,Bacteria_1239).
• high(“person”,Bacteria_1234).
• helps(Person,Modifier) :- high(Person,Taxon),decreases(Modifier,Taxon).
• helps(Person,Modifier) :- low(Person,Taxon),increases(Modifier,Taxon).
• hurts(Person,Modifier) :- low(Person,Taxon),decreases(Modifier,Taxon).
• hurts(Person,Modifier) :- high(Person,Taxon),increases(Modifier,Taxon).
• take(Person,Modifiler) :- remove(helps(Person,Modifier),is,hurts(Person,Modifier)).
• contradict(Modifier,Taxon) :- decreases(Modifier,Taxon),increases(Modifier,Taxon).

“take” above says get the list of items that helps and then removes all items that hurts. I.e. only items without contradictions.

The number of lines (statements) to explicitly write Microbiome Prescription in SWI-PROLOG is about 15 million statements. That code code be licensed (for free or nominal cost) to a project of this type so building such a microbiome resource is not needed; rather just augment that data with autism specific data.

One key difference between ESFL is the ability to infer and not just parrot (typical Machine Learning). Bacteria A increases IL 10. A person with SNP ABC has decreased IL 10, thus we can desired to increase Bacteria A for people with SNP ABC.

Vision – Do it For Autism!

I have a web based data entry system (that is being used commercially) that can be made available to the project (with hosting of site and database). We have an almost ready to run system.

The Rub

This is a time consuming process to enter the data and then have the data reviewed (to insure correctness). Typically the people doing the entry and reviews are M.Sc., Ph.D. or M.D. Using students working on their degrees (summer work, part time) to do entry is often a way of keeping costs down. These students typically have access to the full text of articles through their educational institutes.

• Typical time per study/article is 30 minutes to read and enter, 10 minutes to review
• There are 72,000 studies citing Autism on the US National Library of Medicine.
  • A complete coverage would be 36,000 hours or 900 man-weeks or a team of 18 people working full time for a year.
• The expected number of facts will likely be around 120,000.

Facts should be put in a Public Domain Type of License

This allows other groups to continue the work and prevents the need to duplicate the effort of encoding the same studies multiple times. The terms of license should require people that uses and extends it to also make their additional data available under the same terms.

Benefits

One of the key benefit is the identification of gaps in the knowledge base as well as identifying areas where there are contrary results. This allows better funding of research to fill gaps and not duplicate existing work.

A secondary benefit is that it could always be kept current and provide far more specific data for a patient based on all of the information available. The issue of MD’s knowledge being stale or bias is reduced.

What is needed — FUNDING AND MANAGEMENT

The Rub above takes money to happen — even if you are paying students the minimum wage, we quickly get a significant cost. Ideally one or more existing Autism Organizations can be persuaded to partially or fully fund this project.

My own role would be at most, a process consultant. Working Pro Bono.

Some Video on Expert Systems

Any ideas why olive oil would cause severe aggression tantrums?

From a reader

This is an interesting question.. When I see “severe aggression tantrums”, my mind goes to hypoxia (shortage of oxygen delivery to the brain).

The most significant impact of short-term memory loss for a person with hypoxia is that it impairs the ability to retain and recall new or unfamiliar information. Behavioural changes. The person may become more verbally and physically aggressive. They may also have issues with disinhibition

Hypoxia – – common causes, symptoms and treatment

I know that  olea europaea (olive leaf)   is an antimicrobial, that is, it kills off various bacteria and thus could result in Jarisch Herxheimer Reaction (Herx). Many of the symptoms associated with a herx could be explained from hypoxia. This is cited in the literature [Recurrent Jarisch-Herxheimer reaction: case report 2013].

Olive Oil does not have this reputation. When I checked the known impact of Olive Oil, I see that it increases Bilophila which is reported to increase cognitive impairment [2021], cognitive impairment is strongly associated with hypoxia. Olive Oil also decreases/inhibits/kills Prevotella bivia, Prevotella intermedia,Prevotella melaninogenica,Prevotella oris,Prevotella timonensis and Prevotella buccalis. A common by-product of a bacteria being inhibited is a dumping of toxins into the body, triggering inflammation (thus narrowing blood vessels and reducing oxygen delivery).

A continuous monitoring with a Saturated O2 monitor may reveal this shift (it may not, if the inflammation is in the brain — the monitor is unlikely to record it). For myself, I use a relatively cheap smart watch that records SO2 every 10-15 minutes as part of my normal proactive health monitoring, see Monitoring watch for CFS and other Conditions.

This is just a model, with some ability to check the mechanism.

From Social Media

Backstory

• My son is 5.4 years old , he was diagnosed with autism at 22 months of age .
• We have been strict gluten free casein free sugar free no processed food since his diagnosis .
• For almost 2 years we followed the ne chek protocol with olive oil, fish oil and 1/32 spoon of inulin.
• My son was always verbal with alphabets , numbers colors , planets shapes , colors etc and the odd one / two word request sentences but never conversational.
• His receptive language was very poor until maybe the last year where he is able to follow simple one step instructions.
• He now repeats what is said to him and can answer to what is your name and other v simple questions .
• He is not potty trained and does not understand social norms . He interacts with family members and other adults ( other adults mostly for his needs ) 
• He eats mainly veg and chicken , fish or lamb . Occasionally rice but mostly carb free.
• He consumes a lot of bananas in a day (5-6).

Foreword – and Reminder

I am not a licensed medical professional and there are strict laws where I live about “appearing to practice medicine”.  I am safe when it is “academic models” and I keep to the language of science, especially statistics. I am not safe when the explanations have possible overtones of advising a patient instead of presenting data to be evaluated by a medical professional before implementing.

I cannot tell people what they should take or not take. I can inform people items that have better odds of improving their microbiome as a results on numeric calculations. I am a trained experienced statistician with appropriate degrees and professional memberships. All suggestions should be reviewed by your medical professional before starting.

Reminder: the purpose of these posts is show the process. Every individual will get different suggestions, the suggestions should not be used viewed as suggestions for any symptom or condition.

For more posts on Autism and the Microbiome

Proforma Overview

The percentile overview shows a moderate bias toward rarer bacteria.

Percentile	Genus	Species
0 – 9	22	37
10 – 19	22	21
20 – 29	17	13
30 – 39	8	12
40 – 49	11	14
50 – 59	4	6
60 – 69	9	12
70 – 79	11	17
80 – 89	12	15
90 – 99	11	16

Potential Medical Conditions Detected has two very interesting items over 90%ile matches, namely:

• Brain Trauma (99%ile)
• Schizophrenia (98%ile)
• For Autism he is down at the 81%ile

Other items over 90% tend to be age related, i.e. Alopecia (Hair Loss), hypertension (High Blood Pressure)

Dr. Jason Hawrelak Recommendations came in at 95.6%ile healthy, so no issue there

Since the interpretation of the microbiome data was done thru biomesight, we see that the top matches include:

• Depression
• Autism
• Easily Irritated
• Brain Fog
• Neurocognitive: Attention, Memory, Focus

We have 8 significant pattern matches above and will use each to build a consensus of suggestions. A pattern match means that both of the following appear correct: microbiome pattern matches, the patients symptoms or issue are a reasonable match.

Speculation: The brain trauma and schizophrenia being a much stronger match than autism hints that this child issue may be more related to the microbiome than autism proper.

Consensus Overview

Probiotics

The top item using KEGG data was, Escherichia coli, the prescript assist/equilibrium bacteria and then Bacillus thuringiensis, Bacillus subtilis, Bacillus subtilis subsp. natto, Bacillus amyloliquefaciens, Bacillus licheniformis – further down the list, Akkermansia muciniphila.

We have agreement between two very different paths of picking them (i.e. one by using the genomics of the microbiome and looking at the genomics of the probiotics; the other was using clinical studies reporting desired shifts for the bacteria that was selected). To put some specific brands (when not named above) see this list.

Supplements and Food

Iron (Ferric citrate), Magnesium, l-citrulline, propionate, Reduce choline (Beef, Chicken Eggs) – i.e. more fish, cranberry bean flour or cranberries, blackcurrant, blueberry hydrogenated palm oil, Pulses (pea (fiber, protein), navy bean), Cottage Cheese, berberine, stevia, d-ribose, galactose (milk sugar), lactose.

Many of the above are clustered, i.e. d-ribose and e.coli probiotics (one feeds the other); high saturated milk fat diet and (cottage cheese, galactose, lactose).

Diet style

The Avoids

The avoidance list is rich in “you should be taking items” suggested on the social media on the internet. In fact, they are contrary to the pattern that I typically see with ME/CFS or Long COVID. Everyone is different and it is good to do an evidence based approach for suggestions.

Questions and Answers

Readers usually get a chance to provide more information and ask questions before postings.

Q: we have been on a strict diet for our son, mainly we have not been doing GF/CF diet. Do you recommend moving to a full diet, i.e giving him milk and Gluten.

A: Milk and milk products – yes. Chocolate milk made with real Cacao is supported by the suggestions. 
I checked gluten items:

• Gluten Free was a mild negative (-25) but checking for specific gluten foods, they were all more negative
• Wheat was also a negative – 103
• Oats was also a negative -32
• Barley was also a negative -146
  
  So, I would suggest keeping him gluten free

Q: (From Social Media): “I wonder what the effect is/was of 5 to 6 bananas a day”

A: In the suggestions, bananas was listed as a take in terms of the microbiome. Potassium is a factor for some autism (not all):

• Potassium channels and autism spectrum disorder: An overview [2021]
• Update on the implication of potassium channels in autism: K⁺ channel autism spectrum disorder [2015]
• One parent of a child with Autism experience is given in this post: Potassium may play an important role in Autistic Behaviors [2013]

The message from the parent was clear and with lots of documentation

 My 5 y.o. daughter is having major gut issues for which I am seeking your help. She is having these issues since her birth and we just stand helpless while she cries most of the night.  I have made an excel sheet explaining all her issues for your reference. I am also attaching  her Biomesight.csv file, HTMA Test, GI Map test and her other medical test and stool test results for your kind reference. 

Gut Issues	Sensory Issues	General Behaviour	Socialization	Speech	History, Curent Supplements & Diet
Excessive Gas mostly in evening and night.	Hitting Hard Objects/Plastic in the front teeth	No aggression , no self injurious behaviours	Doesn’t have age appropraite play behaviour	No true words. Only few nonsense syllables	Birth weight-3.45 kg. C-Section delivery.
Bloating	Crashing & Jumping on couch & bed.	Sweet frendly kid. Attention seeker.	More afectionate to adults than kids.	Started comprehending two word commands with gestures	She had several doses of Antibiotics due to flu, fever on more than 5 occasions. She had a teeth infection for which she was given antibiotics. She also had some gut bug for which she vomited more than 12 times in a single night, in the past (at the age of 20 months)
Fatulence/Burps	Looking from the corner of the eye.	Scratching others	Near Normal Eye Contact and Sitting behaviour.	Child expresses her needs through hand leading and dragging parents towards the desired object.	Child gained a lot of weight since childhood. She was 22kg at the age of 2.5 years. Now she is 40kg. Her height is 120 cm
Undigested food in stool mostly vegetables	Rocking back & forth while standing.	Biting other	Poor Focus & Attention		Celiac test is negative. Low in Vitamin D & Iron. Ultrasound test of abdomen is normal
Constipation. Bristol Stool Chart No.-3/4	Making sudden loud noises	Pinching & Hitting others	Shows no interest/high resistance  to any learning activity. Escape behaviour		Supplement– SunFiber, Liver Sauce, Chamomile Tea, Sodium BiCarbonate to relieve gas issues.
There is immediate relief as soon as she passes the gas through fart or burps.	Unusual laughter/ Teeth Grinding (Occassionally)	Restlessness, Crying and Yelling			Diet -GFCFSF diet. Vegetables- Okra, potato, carrots, beans, tomato,snow peas. Other food- boiled chicken, low GI- rice, millet, gluten free flour, gluten/diary free cookies. Fruits- Banana, kiwi, apples.
	Stifening of whole body and hitting with her finger tips	All the above problematic behaviour is noticed when the kid has gut issues
	Hitting her face on gym ball/mattress
	Hand Twirling infront of her face.

Initial Review

My expertise is statistics associated with the microbiome, not autism (although I am a high functioning ASD person).

First looking at distributions we see a predominance of rare bacteria. Usually that hints at herbs to reduce their numbers. Dr. Jason Hawrelak Recommendations placed her at the 95.6%ile, so a main stream solution is unlikely.

Looking at the unhealthy bacteria, several stands out as items of concern:

• Escherichia coli – which are likely the unhealthy ones. This immediately causes me to suggest either Mutaflor (available where she lives) or Symbioflor-2, the good E.Coli probiotics. Given her age, I would start with Symbioflor-2 because it is given in drops and thus we can slowly ramp up (to avoid severe adverse effects). The other option would be to repackage one capsules of Mutaflor in eight capsules and start with lower dosages. Given the symptoms above — this would be my first course of action if it was my child.
• Bacteroides fragilis is high. In terms of non-prescription, pomegranate, lactobacillus reuteri (probiotics), N-Acetyl Cysteine (NAC), Cacao and Mangosteen are the most documented. REMEMBER: There is no literature on relative effects, the Confidence on suggestions is based on the number of studies showing desired effects on the number of bacteria we selected to alter.
• Serratia is also high. Usually associated with urinary tract infections. For this, we have less literature. I would suggest neem tea and perhaps  lactobacillus casei (probiotics)

At this point we have a little dilemma — Escherichia coli and Lactobacillus are hostile to each other, so it’s an either/or. I would usually resolve it by 2 weeks on one and then 2 weeks on the other, recording any changes seen.

Given the history of needing antibiotics in the past, I looked at the computed suggestions. If the needs arise again, see if your MD is willing to use any of the following:

1. macrolide ((antibiotic)s)   (0.444)
2. imipenem (antibiotic)s   (0.382)
3. fluoroquinolone (antibiotic)s   (0.337)
4. ciprofloxacin (antibiotic)s   (0.305)
5. clindamycin (antibiotic)s   (0.294)
6. erythromycin (antibiotic)   (0.274)

Please make sure that you check risk factors for the above, especially given her age. For example, fluoroquinolone has many! The above were calculated solely on the microbiome impact, not risk factors.

Other Medical Reports

After the first impressions above, I went to look at the other test results

• Hair shows slightly out of range for Arsenic (common for ASD)
• Celiac tests: negative
• Cortisol: in range
• Lipid Profile: normal
• Serum Free T3+Free T4+TSH: normal
• Ultrasound: normal
• Vitamin D + Iron: normal
• Gastrointestinal Pathogen PCR (Stool): Negative
• Liver Function: normal except for
  • Alkaline Phosphatase: high (2x upper limit)
  • Sodium and Potassium – slightly high (similar on hair above)
• GI Map
  • Bacteroides fragilis: High, as above
  • Enterococcus: High (versus 18%ile, low on Biomesight results)
  • Escherichia species: At top of reference range (97%ile on Biomesight results)
  • Akkermansia Munciniphila: none detected (none detected on Biomesight results)
  • Zonulin [literature] was very high indicating leaky gut.

Looking at Biomesight results

• Bacillus was not high
• None of the Enterococcus were reported and the family was a little low
• Morganella was not reported
• S. Aureus was not reported
• Streptococcus was low

I will make the assumption that at least one round of antibiotics were done between the GI Map (Mar 29,2022) results and the Biomesight results — although I have read studies questioning the reliability of some GI Map results.

Probable Symptoms

This was recently revised, and seems to match — especially the time since offset.

Symptom	Matches
less than 04 years since onset	77
Frequently loose train of thought	75
Lyme	74
Less Avoidance of Eye Contact or Poor Eye Contact	73

Where Do we go from here?

I picked the following to build the consensus report shown below:

• Special Studies: Autism (75)
• Special Studies: Inflammatory bowel disease ( 86 candidate bacteria) – given all of the bowel issues
• JasonH (15 Criteria) – just 7
• Standard Lab Ranges (+/- 2 Std Dev) – just 7
•  Box Plot Whisker – 45
•  Kaltoft-Moltrup Normal Ranges – 109
•  Percentile in top or bottom 10% – 134

It was interesting to note that the methods that selected the most bacteria, were the special studies, KM and the top/bottom 10%.

Consensus Suggestions

As always, the full consensus report is attached.

In reviewing the list, the ones that I would be most inclined to use are:

• Triphala
• Bofutsushosan (which will encourage Akkermansia!)
• Omega-3 fatty acids
• Lactobacillus rhamnosus (probiotics),
• berberine

I should note that symbioflor 2 e.coli probiotics is on the avoid list — this often happens when there is a need to increase lactobacillus which was sitting at 6%ile. When lactobacillus is low, I tend to ignore the avoid on E.Coli probiotics and point out the mutual hostility they have – so do one and then the other, noticing any changes (the one that gives the best positive change, do more of — but keep rotating). I usually suggest starting with the E.Coli probiotics because they are known to persist. This is rarely the case for Lactobacillus probiotics.

People who have uploaded their (or their children) samples have annotated some with easily irritated. On my main blog, I have been doing a series of deep statistical dives on my main microbiome blog site, and checked it the data available reaches the threshold for inclusion as defined in A new specialized selection of suggestions links (A summary table of various studies has been added there).

I am posting here to since it is a blog focused on Autism and easily irritated is a common symptom.

Study Populations:

Symptom	Reference	Study
Easily irritated	1108	55

• Bacteria Detected with z-score > 2.6: found 146 items, highest value was 9.9
• Enzymes Detected with z-score > 2.6: found 896 items, highest value was 5.9
• Compound Detected with z-score > 2.6: found ZERO items

For the number of samples, the z-score for bacteria are unusually high compared to other studies in the series. A high z-score means strong statistical significance. Enzymes has a huge numbers detected without any extreme values – this is interesting but unsure on how to interpret that.

Interesting Significant Bacteria

• All bacteria found significant had too low levels

The most significant ones are listed below. I should point out that these bacteria may not be the cause, rather they may be ‘the canaries in the coal mine’ of the microbiome. These studies’ methodology determines association and not causality.

Bacteria	Reference Mean	Study	Z-Score
Prevotella oulorum (species)	63	17	9.9
Prevotella copri (species)	65522	9089	8.8
Clostridium malenominatum (species)	57	22	6.3
Pediococcus (genus)	112	48	6.1
Phocaeicola coprocola (species)	7544	45	6.1
Actinobacillus pleuropneumoniae (species)	57	19	6
Opitutae (class)	169	43	5.8
Puniceicoccaceae (family)	163	40	5.8
Lactiplantibacillus pentosus (species)	122	17	5.8
Bifidobacterium cuniculi (species)	81	25	5.7
Cerasicoccus arenae (species)	552	87	5.5
Prevotella (genus)	73346	26681	5.5
Puniceicoccales (order)	114	35	5.4
Veillonella (genus)	4004	1945	5.4
Cerasicoccus (genus)	319	56	5.3
Tenericutes (phylum)	3138	1053	5.1

Interesting Enzymes

The first 100 enzymes (of 800+) found significant had too low levels.

Enzyme	Reference Mean	Study Mean	Z-Score
propanoyl-CoA:NADP+ oxidoreductase (1.3.1.84)	29	10	5.9
S-methyl-5′-thioadenosine:phosphate S-methyl-5-thio-alpha-D-ribosyl-transferase (2.4.2.28)	3653	1426	5.8
3-oxo-Delta1-steroid:acceptor 1-oxidoreductase (1.17.99.11)	28	10	5.7
cholest-4-en-3-one:acceptor oxidoreductase (25-hydroxylating) (1.17.99.10)	28	10	5.7
n/a (3.4.24.20)	40	16	5.2
malonyl-CoA:acetate malonyltransferase (tetracenomycin-F2-forming) (2.3.1.235)	41	11	5.2
malonyl-CoA:malonamoyl-[OxyC acyl-carrier protein] malonyltransferase (2.3.1.260)	41	11	5.2
NADPH:acceptor oxidoreductase (1.6.99.1)	5726	2382	4.8

I will leave it to the reader to go to Kyoto Encyclopedia of Genes and Genomes to learn about these enzymes (a steep learning curve).

The top item S-adenosyl-L-methionine (SAMe), had significant literature associated with it, a few samples:

• “S-adenosyl methionine prevents ASD like behaviors triggered by…” [2019]
• “S-Adenosyl-Methionine alleviates sociability aversion and reduces changes in gene expression in a mouse model of social hierarchy” [2022]
• “Blood biomarker levels of methylation capacity in autism spectrum disorder: a systematic review and meta-analysis” [2020] – decrease SAMe in blood
  

Enzyme	Reference Mean	Study Mean	Z-Score
S-adenosyl-L-methionine:23S rRNA (guanine2535-N1)-methyltransferase (2.1.1.209)	151	70	7.6
GDP-alpha-D-rhamnose:NAD(P)+ 4-oxidoreductase (1.1.1.281)	481	120	6.4
ATP:D-galacturonate 1-phosphotransferase (2.7.1.44)	506	120	5.7
NAD+:poly(ADP-D-ribosyl)-acceptor ADP-D-ribosyl-transferase (2.4.2.30)	505	120	5.6
beta-D-galactosyl-(1->4)-L-rhamnose:phosphate 1-alpha-D-galactosyltransferase (2.4.1.247)	505	120	5.6
delta/gamma-tocopherol lyase (ring-opening) (5.5.1.24)	703	213	5.6
all-trans-heptaprenyl-diphosphate diphosphate-lyase (cyclizing, tetraprenyl-beta-curcumene-forming) (4.2.3.130)	304	157	4.7
CDP-diacylglycerol:myo-inositol 3-phosphatidyltransferase (2.7.8.11)	133	88	4.6
Hg:NADP+ oxidoreductase (1.16.1.1)	774	195	4.6
ferredoxin:dinitrogen oxidoreductase (ATP-hydrolysing, molybdenum-dependent) (1.18.6.1)	2930	1478	4.4
myo-inositol-hexakisphosphate 4-phosphohydrolase (3.1.3.26)	2163	1074	4.2
phenol,NADPH:oxygen oxidoreductase (2-hydroxylating) (1.14.13.7)	326	51	4.1
1,2-beta-D-glucan:phosphate alpha-D-glucosyltransferase (2.4.1.333)	264	128	4
acetyl-CoA:2-oxoglutarate C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming) (2.3.3.14)	936	341	4

Cross Validation To Literature

The term “irritability” on PubMed often links to  irritable bowel syndrome (IBS), making this difficult. The closest proxy appears to be stress (most people that are stressed tend to be irritable…) and there was some matches. We have agreement on the following being low.

• Atopobium
• Lactiplantibacillus plantarum
• Anaeroplasma
• Coriobacterium
• Tenericutes

Bottom Line

Lactiplantibacillus plantarum is the modern name for Lactobacillus Plantarum, a commonly available probiotic.

People who have uploaded their (or their children) samples have annotated some with Autism. On my main blog, I have been doing a series of deep statistical dives on my main microbiome blog site, and checked it the data available reaches the threshold for inclusion as defined in A new specialized selection of suggestions links (A summary table of various studies has been added there).

I am posting here to since it is a blog focused on Autism.

Study Populations:

Symptom	Reference	Study
Bloating	1082	67

• Bacteria Detected with z-score > 2.6: found 196 items, highest value was 8.2
• Enzymes Detected with z-score > 2.6: found 203 items, highest value was 7.6
• Compound Detected with z-score > 2.6: found ZERO items

For the number of samples, the z-score are unusually high compared to other studies in the series. A high z-score means strong statistical significance.

Interesting Significant Bacteria

All bacteria found significant had too low levels with the exception of the following that was too high:

• Prevotellaceae (family)
  • Prevotella copri (species)
  • Prevotella veroralis (species)
• Bifidobacterium gallicum (species)
• Peptococcaceae (family)

The most significant ones are listed below. I should point out that these bacteria may not be the cause, rather they may be ‘the canaries in the coal mine’ of the microbiome. These studies’ methodology determines association and not causality.

Bacteria	Reference Mean	Study	Z-Score
Acholeplasma (genus)	1421	215	8.2
Pseudoclostridium (genus)	146	70	7
Pseudoclostridium thermosuccinogenes (species)	145	70	7
Bacteroides rodentium (species)	3371	1481	6.9
Anaerovibrio lipolyticus (species)	1328	355	6.7
Anaerovibrio (genus)	1344	368	6.7
Anaerotruncus (genus)	1929	1150	6
Butyrivibrio (genus)	519	120	5.8
Xanthomonadaceae (family)	820	266	5.8
Blautia hydrogenotrophica (species)	252	73	5.7
Thiotrichaceae (family)	179	75	5.6
Thiothrix (genus)	179	75	5.6
Butyrivibrio proteoclasticus (species)	498	120	5.6
Thiotrichales (order)	179	78	5.5
Adlercreutzia equolifaciens (species)	232	90	5.5
Anaerotruncus colihominis (species)	1833	1140	5.4
Rubritalea (genus)	61	27	5.3

Interesting Enzymes

All enzymes found significant had too low levels.

I will leave it to the reader to go to Kyoto Encyclopedia of Genes and Genomes to learn about these enzymes (a steep learning curve).

The top item S-adenosyl-L-methionine (SAMe), had significant literature associated with it, a few samples:

• “S-adenosyl methionine prevents ASD like behaviors triggered by…” [2019]
• “S-Adenosyl-Methionine alleviates sociability aversion and reduces changes in gene expression in a mouse model of social hierarchy” [2022]
• “Blood biomarker levels of methylation capacity in autism spectrum disorder: a systematic review and meta-analysis” [2020] – decrease SAMe in blood
  

Enzyme	Reference Mean	Study Mean	Z-Score
S-adenosyl-L-methionine:23S rRNA (guanine2535-N1)-methyltransferase (2.1.1.209)	151	70	7.6
GDP-alpha-D-rhamnose:NAD(P)+ 4-oxidoreductase (1.1.1.281)	481	120	6.4
ATP:D-galacturonate 1-phosphotransferase (2.7.1.44)	506	120	5.7
NAD+:poly(ADP-D-ribosyl)-acceptor ADP-D-ribosyl-transferase (2.4.2.30)	505	120	5.6
beta-D-galactosyl-(1->4)-L-rhamnose:phosphate 1-alpha-D-galactosyltransferase (2.4.1.247)	505	120	5.6
delta/gamma-tocopherol lyase (ring-opening) (5.5.1.24)	703	213	5.6
all-trans-heptaprenyl-diphosphate diphosphate-lyase (cyclizing, tetraprenyl-beta-curcumene-forming) (4.2.3.130)	304	157	4.7
CDP-diacylglycerol:myo-inositol 3-phosphatidyltransferase (2.7.8.11)	133	88	4.6
Hg:NADP+ oxidoreductase (1.16.1.1)	774	195	4.6
ferredoxin:dinitrogen oxidoreductase (ATP-hydrolysing, molybdenum-dependent) (1.18.6.1)	2930	1478	4.4
myo-inositol-hexakisphosphate 4-phosphohydrolase (3.1.3.26)	2163	1074	4.2
phenol,NADPH:oxygen oxidoreductase (2-hydroxylating) (1.14.13.7)	326	51	4.1
1,2-beta-D-glucan:phosphate alpha-D-glucosyltransferase (2.4.1.333)	264	128	4
acetyl-CoA:2-oxoglutarate C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming) (2.3.3.14)	936	341	4

Cross Validation To Literature

Using microbiome studies from published studies is often difficult because the results often vary greatly due to the lab equipment used and the software used to interpret the data.

Checking against the literature we found:

• Items reported High
  • Prevotellaceae (NCBI:171552 ) is low in three studies, we found it high
  • Prevotella copri (NCBI:165179 ) is report low in one study and high in one study
  • Bifidobacterium (NCBI:1678 ) is reported low in some studies and high in other studies
  • Peptococcaceae is not reported in the literature
• Items Reported Low – none are reported in the literature

The purpose of these studies is to enable apple-to-apple-to-apple analysis and suggestions. The same lab is used for the raw read (Ombre and Biomesight uses the same lab) and all of the data is processed thru the same software (BiomeSight). Your sample (if you use the website) is processed thru the same process.

A final comment on most published studies, typically there are 25 Autism patients and 25 control patients. This actually results in much lower sensitivity in those studies than we have with over 1000 as the control.

Bottom Line

The SAMe “shouting out” in the enzymes being in agreement with published studies causes me to have considerable confidence in the analysis. Dr. Artificial Intelligence suggestions on Microbiome Prescription look like they are likely to have positive results.

P.S. If anyone does more drill down into the enzymes above in the literature, feel free to add your findings as comments.