Autism and the Microbiome

Lately I have been getting a number of inquiries of parents with children with autism. I am a high function autism spectrum person myself, the degree of focus on the microbiome is likely a tell-tale ;-). I have done a few prior posts, and will keep my citations to studies after these posts.

If you find this informative, please share on groups you belong to.

Can we modify Autism by Microbiome adjustment?

In short, the answer is yes — but apart from FMT, researchers/clinicians are tossing random diet and probiotics at the issue resulting is very mixed results.

Bacteria Shifts

” This meta-analysis suggests an association between ASD and alteration of microbiota composition and warrants additional prospective cohort studies to evaluate the association of bacterial changes with ASD symptoms, which would provide further evidence for the precise microbiological treatment of ASD. ” [2019]

For a good summary of current research see Table 2 in The Role of Gut Microbiota in Gastrointestinal Symptoms of Children with ASD [2019] or my condition summary page. In both of these you will see disagreement on some results: for example Lactobacillus to high compared to the controls used in one study and Lactobacillus is low compared to the controls used in another study. To me, this means that it is the metabolites being produced is the likely cause. Different groupings of bacteria can present with a similar metabolite profile. Often members in one of these grouping may be hostile to members of a different grouping — looking for a single bacteria or a single pattern of bacteria is a naive understanding of the microbiome.

” Serum levels of TNFα, TGFβ, NT, and SORT-1 increased in ASD patients. Fecal levels of HMGB1 correlated with GI sign severity in ASD children. ‘” [2019]

In terms of the microbiome site, we are up to 12 samples with autism uploaded. 16 is the threshold for it to showup in the symptom explorer (20-30 samples would be really nice!)

Attempts to date

 Nowadays, there is lack of strong evidence about the effect of dietary interventions on these problems, particularly prebiotics. Therefore, we assessed the impact of exclusion diets and a 6-week Bimuno® galactooligosaccharide (B-GOS®) prebiotic intervention in 30 autistic children…. Following B-GOS® intervention, we observed improvements in anti-social behaviour, significant increase of Lachnospiraceae family, and significant changes in faecal and urine metabolites.

A prebiotic intervention study in children with autism spectrum disorders (ASDs). [2018]

Consistent with previous studies, the microbiota of children with ASD contained a higher number of Clostridium spp. and a lower number of bifidobacteria compared with non-autistic children. B-GOS administration significantly increased bifidobacterial populations in each compartment of the models, both with autistic and non-autistic-derived samples, and lactobacilli in the final vessel of non-autistic models. In addition, changes in other bacterial population have been seen in particular for Clostridium, Rosburia, Bacteroides, Atopobium, Faecalibacterium prausnitzii, Sutterella spp. and Veillonellaceae. Furthermore, the addition of B-GOS to the models significantly altered short-chain fatty acid production in both groups, and increased ethanol and lactate in autistic children. “

In vitro fermentation of B-GOS: impact on faecal bacterial populations and metabolic activity inautistic and non-autistic children. [2017] ”

Bottom Line

It is clear that microbiome shifts impacts the severity and symptoms of ASD. Two studies showed improvements by trying to alter the microbiome, in one case by a probiotic and in the other case a prebiotic. IMHO, any drug that helps ASD, probably helps it by the microbiome shift it induces.

It is unlikely that the natures of the shifts are identical — we are dealing with different shifts for different patients. If you are the parent of an ASD child you have several paths before you:

  • Use the results of the two studies above, seeking out the specific strain and prebiotic used. Watching for further studies over the next decade
  • Wait until some breakthru happens in the future
  • Do a 16s analysis (list of providers here) and use the microbiome prescription site to get suggestions to review with your child’s MD.
    • Suggestions included probiotics that are theoretically more likely to help than hurt.
    • The suggestions can be further refined by including symptoms (which highlights certain patterns in the midst of the noise).
  • Go with random suggestions from support groups. Often improvements reported are placebo effects or ‘hopeful glasses’ reports (you see what you need to see, not what is there).

As a FYI — my last post linked to an a priori suggestions for Autism (suggestion based on the shifts reported in the literature). The first probiotic on that list was Lactobacillus Plantarum. Also at the top of the lists were arabinoxylan oligosaccharides (prebiotic), fructo-oligosaccharides (prebiotic) . In other words, we have convergence of predicted to reported from studies.

Probiotics for mouth, sinus and eyes

A reader wrote me about problems with chronic congestion. While in theory, altering gut bacteria may be able to influence this is a roundabout way (alter metabolites circulating in the body), this does not seem the most direct and best route.

Recently I wrote about Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function. [Sep 2018] in this post. The purpose of the post was to try to explicitly address the oral microbiome found with ME/CFS. There are very very few studies looking at the oral microbiome.

As a result of this post, I did some ‘biohack’ experiments that had surprising good results. I used two probiotics available as hard tablets (not capsules) under the tongue at bed time. Chronic low grade congestion disappeared in a few days. A little further digging over the weekend end up revealing that it may also help with periodontal issues! (I have seen some improvement there also)

What dd I take?

  • Miyarisan Clostridium butyricum MIYAIRI 588
  • Biofermin “S
    • Streptococcus faecalis 129 BIO 3B (SF3B: strain currently classified as Enterococcus faecium. Human sourced).
    • Lactobacillus Acidophilus KS-13 
    • Bifidobacterium Bifidum G9-1

Before explaining what this may be happening, let us check what is in the literature:

What is on PubMed

Oral Microbiome Studies of Interest

And many more.

The Problems

  • So far, I have had 4-6 mouth and nose samples uploaded. Not sufficient to do any analysis on 😦
  • There is practically no literature on modifying the oral microbiome.
  • Modifying the gut microbiome addresses systemic issues, the impact on the sinus, mouth and eye would be very indirect.

What is known (and explaining my results)

Symbioflor-1 is studied with positive results, it is a human source Enterococcus faecalis. Biofermin S is also Enterococcus faecalis, so the positive effects seen are not a surprise.

For Miyarisan (Clostridium butyricum MIYAIRI 588) we have no direct studies but there is plausible explanation based on studies. First I need to introduce you to LL-37

Next, we find that that it increases with severe periodontitis, Gingival crevicular fluid and serum hCAP18/LL-37 levels in generalized aggressive periodontitis.[2017] Since it is an antimicrobial, it is reasonable to speculate that the increase was the body way to fight the peridontitis!

We now add in butyrate – what is produced by Miyarisan

Recent studies demonstrated that butyrate induces LL-37 mRNA in colonic epithelial cells, however the underlying molecular mechanisms have not been elucidated…. Our results clearly demonstrate that butyrate-mediated up-regulation of LL-37 is influenced by several signalling pathways and receptors including MAPKs as well as VDR and TGF-beta1, but not by PPARgamma.   

Role of nuclear hormone receptors in butyrate-mediated up-regulation of the antimicrobial peptide cathelicidin in epithelial colorectal cells.[2007]

So the chain is this: Miyarisan increases butyrate in the oral cavity, this then pushes up the output of LL-37 and periodontitis is reduced. In theory, using sodium butyrate under the tongue may have similar effects. The advantage of Miyarisan is that it will likely contribute longer and have other antimicrobial actions.

Bottom Line

This post is closer to bio-hacking speculation than my usual “Just the studies, ma’am. Just the studies”.

Dragnet: Sgt Joe Friday (TV Show)

If the critical issue is in these areas, the suggestions for the entire body from http://microbiomeprescription.com/ may be a poor fit. The studies on enterococcus faecalis and LL-37 suggests that the above may be able to effect sinus, periodontitis and perhaps dry-eye issues. They are in the same sphere and far removed from the gut.

If I get at least 16 samples for each of these non-gut areas, I will spin out some of the charts for them. A suggestion engines needs facts from studies — and that we do not have. What I have is on this page.

Sources

https://www.symbiopharm.de/en/products/symbioflorr-1.html

An alternative if you intend to do a nasal wash could be: AOR/Probiotic-3 which contains the same key items. It is a capsule.

  1. bacillus subtilis
  2. clostridium butyricum
  3. enterococcus faecium

An Alternative Model for Depression and Anxiety

Studies have shown there are differences between depression from Chronic Fatigue Syndrome and classic depression as well as the microbiome findings:

Depression and the Microbiome Revisited

An older model that I have used has been hypoxia a.k.a. Altitude Sickness. The reason were originally the overlap of many symptoms between CFS and Altitude Sickness. After that, I was tested for Hypercoagulation by Hemex Labs (Coagulation specialists) and found that I was — in fact hypercoagulated. For some blood draws the nurse ended up trying 8 different sites before they could get enough blood! Talk about thick blood!

A study at that time found 85% of CFS/ME patients were hypercoagulated with many improving greatly from low dosage heparin.

And thick blood means slow moving blood and thus the delivery rate of oxygen goes down.

https://medlineplus.gov/ency/article/000133.htm

Observed behaviors and personal anecdotes suggest that the initial mood experienced at altitude is euphoria, followed by depression. With time, individuals may also become quarrelsome, irritable, anxious, and apathetic (Van Liere and Stickney, 1963). Unfortunately, although disturbances in emotional control have been noticed at altitude for decades, there are few quantitative studies assessing mood changes at altitude.

The Effect of Altitude on Cognitive Performance and Mood States

So I have low oxygen levels – What can I do?

The ‘obvious’ suggestions rarely work. An example:

  • Oxygen tank:
    • Will not work for slow blood. The blood may already be saturated with oxygen
    • Will not work if there are hemoglobin issues. The blood cannot carry more

IMHO there is not one universal solution, the following are possibly (depends on the person’s actual conditions)

Bottom Line

The above looks at items that in terms of a delivery network could be described below

  • Increases the speed on the highways (blood flow)
  • Adds more lanes to the highways ( Vascular Dilators )
  • Repairs the road surface (120km/hr on a pothole road does not do it)
  • Increase the load each trunk can carry
  • Improves the routing and utilization of each truck (nootropics)

The goods being delivered is oxygen, the road system is your body.

Very Strong and Strong Association of Bacteria to Symptoms

I have added two new pages:

When you click on the name, you will be taken to the numbers used (keeps everyone honest!)

In some case we can conclude that very low values are associated
Other cases lower
In other cases, it is not a linear relationship, rather a tend to be higher than most BUT not in the highest range. This is detected because we are not trying to fit a straight line to the data.

Is there evidence that uBiome quality has fallen?

Given the issues they have with the corporate management and governance, some readers asked if their apparent quality has dropped.

Quality means the number of bacteria detected in a sample. This is a valid question — quality control and processing may have taken a hit. Since most of these processes are heavily automated… I do not expect any major changes. Since I have access to 800+ ubiome done samples, I thought that I would take a peak.

Over the entire period, quality appear to be going up slightly.

Reducing our scope to just 2019, we no loss of quality and the same upward trend

Bottom Line

No evidence of loss of quality