A reader asked me to do a review of Spectrumceuticals Pro4-50 D-Lactate Free Probiotics which contains

•  L. rhamnosus,
• B. lactis,
• B. breve and 
• B. longum. 

Custom Probiotics offers a similar one labeled with the strains.

• L. Rhamnosus, Strain LR-32
• L. Salivarius, Strain LS-33
• B. Lactis, Strain BL-04
• B. Bifidum, Strain Bb-06
• B. Infantis, Strain Bi-26
• B. Longum, Strain BL-05

The latest incursions into the probiotic market of claims have posited the amelioration of oxidative stress via potent antioxidant attributes or limiting the administration of probiotics to those species that do not produce D-Lactic acid (i.e., claims that D-Lactic acid acidosis is linked to chronic health conditions)..there is no place in science and medicine that supports unsubstantiated claims. Extravagant industry based notions continue to fuel the imprimatur of distrust and skepticism that is leveled by scientists and clinicians at an industry that is already rife with scientific and medical distrust and questionable views on probiotics. 

Probiotics, D-Lactic acidosis, oxidative stress and strain specificity [2017]

We should note a few things from the literature:

• ” Gut permeability markers (D-lactate and diamine oxidase (DAO))  …. the serum DAO activity and D-lactate concentration significantly increased by fluoride” [2020]
  • Translation: No fluoride toothpaste or fluoridated water (beware of bottled water – it’s often sourced from civil fluoridated water systems)
• “The indicators of intestinal mucosal barrier function, such as D–lactate, endotoxin, and diamine oxidase, were significantly improved and the systemic inflammation (interleukin 10) was attenuated after probiotic [live Clostridium butyricum plus Bifidobacterium infantis] therapy. “
• “D-lactic acidosis is characterized by brain fogginess (BF) and elevated D-lactate and occurs in short bowel syndrome….  SIBO was more prevalent in BF than non-BF group.  After discontinuation of probiotics and a course of antibiotics, BF resolved and gastrointestinal symptoms improved significantly (p = 0.005) in 23/30 (77%).”  [2018]
• “Compared with control, d-lactate content, diamine oxidase activity, and adrenocorticotropic hormone level in serum decreased significantly [with Bacillus licheniformis]” [2013]
• “a stand-alone synbiotic treatment was started, specifically Bifidobacterium breve Yakult and Lactobacillus casei Shirota as probiotics, and galacto-oligosaccharide as a prebiotic. Serum D-lactate levels declined, and the patient has been recurrence-free for 3 years without dietary restriction.’ [2013]
• ” she was treated with sodium bicarbonate and oral antibiotics. The probiotics the patient had taken were likely the cause of D-lactic acidosis and should therefore be avoided in patients with short bowel syndrome.” [2009]

The reader requesting this review cited “Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons’ 2018. Which used the above mixture. “A small, negative correlation was observed between change in D:L lactate concentration ratios and change in Streptococcus count for the total sample (r _s  = − .243, p = .142). ” This is NOT STATISTICALLY SIGNIFICANT ( p < 0.01 is what we want to see). In fact, a chart in it illustrated the problem of using averages with the microbiome.

Bottom Line

The apparent reason for the promotion of D-Lactate Free probiotics is to reduce D-Lactate levels. There is no gold standard (or even silver standard) evidence that the above probiotics will do that. The dominant successful way of treating D-Lactic Acidosis is with antibiotics and avoidance of probiotics.

The best documented, all probiotic treatment is:

• Clostridium butyricum plus Bifidobacterium infantis

Promoter’s Moral Obligation

IMHO, the promoter of these products is under a moral obligation to demonstrate with a study that they work. For these products, a study with 15 control and 15 with brain fog/high d-lactate by lab, is a very very low cost study. Take DAO and D-Lactate readings at start for all, give them the probiotics for 30-90 days, remeasure… then publish. BEAUTIFUL MARKETING MATERIAL. The absence of such publications strongly suggests that this is now pure marketing hype (based on a logical idea and being “sold” on logic and not on evidence based studies). A study likely was done with no (or negative) results – which is exactly what was reported in the above study [that did get published, likely because it was a registered trial].

The Dilemma

The literature indicate that reducing D-Lactate also reduces DAO. Insufficient DAO is associated with Mast-Cell Activation and Histamine issues. There is a need for a balance here. A tightrope that may need to be carefully walked.

Sleep Consequences

Sleep issues in ME/CFS may be connected to excessive D-Lactic acid (A known characteristic of ME/CFS)

Results and conclusion: Administration of L-lactate does not influence sleep-wake cycle of experimental animals. At the same time, its artificial optical analog D-lactate induces the significant (as compared to the control) decrease in wake (34.8% to 26.5%) and increase in slow wave sleep (57.4% to 69.2%). It has been suggested that D-lactate may be the antagonist of one or several L-lactate receptors.

[D-lactate as a novel somnogenic factor?] [2020]

A reader from Romania requested that I do a post on MCAS. It’s of special interest to me because some close friends appear to have this issue. I know from prior posts that there is limited professional knowledge that is effective, and most of it is symptom relief and not addressing the underlying cause.

I recently added a major component to my microbiome analysis site – enzymes from Kyoto Encyclopedia of Genes and Genomes. Witg this, we have had a significant number of microbiome samples shared to the site reporting Comorbid: Histamine or Mast Cell issues. One of the challenges is that there may be some fuzz since this is self reported.

In this post you will see that enzyme imbalances from a microbiome sample can lead to a root cause of some symptoms. In some cases, lead to actions that may moderate the symptom.

The process that I going to use, is simple:

• Look at each species reported in each of 224 people microbiome (over 10,000 different bacteria species)
• Look up the genes in each one of these species.
• Look up which ones of 1600+ Enzymes each gene produced. Most bacteria produces many many enzymes – they have a lot of genes.
• Look at statistically significant oddities in the enzymes of those reporting a certain symptom

When this data is pushed thru some artificial intelligence, one enzymes leaps out for MCAS, lipopolysaccharide 3-alpha-galactosyltransferase.

Four other enzymes are also suspect (and low) but without as strong statistical significance at present, as the one above.

• aureolysin
• lysostaphin
• poly(ribitol-phosphate) alpha-N-acetylglucosaminyltransferase
• 4,4-diapophytoene desaturase (4,4-diapolycopene-forming)

We can also walk this bacteria-to-enzyme path backwards, from the enzymes that are low, we look up the genes that produces it, then from the genes identify the bacteria; as a final step, we see if any commercially available probiotics produces this enzyme. The thinking is simple: if you are short of an enzymes, then increasing enzymes may calm down the processes causing MCAS. We come up with two of them:

• lactobacillus acidophilus
• lactobacillus helveticus

This looks like AI magic, machine learning of other evils of technology. Not quite, we can look for studies dealing with allergies and/or MCAS and see if either of these have been studied. First, we discovered that is not a single study on using the above to treat MCAS. For allergies, histamine reactions, we find significant literature

• Lactobacillus helveticus SBT2171 Alleviates Perennial Allergic Rhinitis in Japanese Adults by Suppressing Eosinophils: A Randomized, Double-Blind, Placebo-Controlled Study [2020]
• Lactobacillus helveticus SBT2171 alleviates allergic symptoms in a murine model for pollen allergy [2019]
• Modulation effect of Lactobacillus acidophilus KLDS 1.0738 on gut microbiota and TLR4 expression in β-lactoglobulin-induced allergic mice model [2019]
• Additive effect of Lactobacillus acidophilus L-92 on children with atopic dermatitis concomitant with food allergy [2019]
• Efficacy of prolonged ingestion of Lactobacillus acidophilus L-92 in adult patients with atopic dermatitis [2016]
• Effects of oral administration of Lactobacillus acidophilus L-92 on the symptoms and serum cytokines of atopic dermatitis in Japanese adults: a double-blind, randomized, clinical trial [2015]
• [Clinical effects of Lactobacillus acidophilus strain L-55-contained yogurt on symptoms of Japanese cedar pollen allergy] [2012]
• Lactobacillus acidophilus strain L-92 induces CD4(+)CD25(+)Foxp3(+) regulatory T cells and suppresses allergic contact dermatitis [2012]

There are additional studies of these two lactobacillus species with other probiotics being effective with allergies (unfortunately with multiple probiotics being involved, things are unclear as to which part is helping). Note that most lactobacillus species do NOT produce this enzyme.

This is a Novel Approach

The body’s circulating metabolites/chemicals imbalances causing symptoms is well accepted. At present, there is testings of a few of the chemicals that can identify to a medical person that there is an imbalance. They do not provide a clear answer on what the source is. With the use of the microbiome down to the species (and strain) levels, we can estimate levels of over 1600 enzymes. If we have a sufficient reference population, we can identify major shifts. We also jump to an understanding of the root cause — which has eluded us before — our microbiome is not producing enough of certain chemicals due to the current composition of the bacteria population.

In the case of MCAS, it is too little of one specific enzyme. This enzyme happens to be produced by two probiotic species. We have also confirmed that these same two species are known to help allergies (but the exact method of helping is often speculated on).

People often want a simple explanation of how it is connected. Unfortunately when dealing with KEGG, we enter the world of a ton of biological wiring as shown by the chart below. This does not means that we can’t use this information; it just means that for most people, the how may be above their formal education and bandwidth.

Let us return to this LOW enzyme for a moment and see what is in the literature about it or what is influenced by it: lipopolysaccharide 3-alpha-galactosyltransferase.

• Lipopolysaccharide-mediated mast cell activation induces IFN-gamma secretion by NK cells [2010]
• Lipopolysaccharide suppresses IgE-mast cell-mediated reactions [2017]
• The Mast Cell Is an Early Activator of Lipopolysaccharide-Induced Neuroinflammation and Blood-Brain Barrier Dysfunction in the Hippocampus [2020]

In other words. this enzyme seems connected to mast cells and its activation. Artificial Intelligence magic applied to a large data store of facts, gave us this enlightenment as to cause and suggestions on how to improve MCAS. We lack any case studies — but given the low risk, it is likely worth trying after consulting with your medical professional.

This same pattern can be applied to dozens of individual symptoms (see this page), or across a microbiome sample as a whole.

Addendum

A comment pointed me to Human diamine oxidase is readily released from activated neutrophils ex vivo and in vivo but is rarely elevated in bacteremic patients [Sep 2020] which contains interesting relevant information:

. DAO antigen levels were also determined in three different subcohorts of patients with culture-proven bacteremia and high C-reactive protein (CRP) levels. DAO concentrations were elevated in a time-dependent manner in serum but not in EDTA or citrate plasma (P < 0.01). Neutrophil activation using phorbol myristate acetate (PMA) and zymosan dose-dependently caused DAO concentrations to be elevated more than 10-fold at both 22°C and 37°C (both P-values <0.001). Administration of LPS to healthy volunteers released DAO from neutrophils (P < 0.001). Of the 55 different bacteremic patients selected from three independent cohorts only 3 (5.4%) showed highly elevated DAO concentrations. Serum DAO concentrations do not accurately reflect circulating enzyme levels but coagulation-induced neutrophil activation and consequently DAO release. Only a few bacteremic patients show high DAO concentrations able to degrade histamine rapidly.

Human diamine oxidase is readily released from activated neutrophils ex vivo and in vivo but is rarely elevated in bacteremic patients [Sep 2020]

Lipopolysaccharide are endotoxins. ” Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents,” This drops a scent in this direction:

• ” Most microorganisms recognized to date as probiotics are Gram-positive, with Lactobacillus and Bifidobacterium being the main species used as treatments of intestinal dysfunctions (Marco et al. 2006). However, some Gram-negatives are also used as probiotics. The best example of this group is Escherichia coli Nissle 1917 (EcN) (Nissle 1959), also known as “Mutaflor,” which has been used in Germany for many years in the treatment of chronic constipation (Mollenbrink and Bruckschen 1994) and colitis (Schutz 1989).” [2013]
• This leads us to K5 Capsule and Lipopolysaccharide Are Important in Resistance to T4 Phage Attack in Probiotic E. coli Strain Nissle 1917 [2019] which suggests that mutaflor (or an engineered version of it) may be a solution to MCAS. Since Mutaflor takes up residency often, it may be a potential cure. Symbioflor-2 (US Source, World Wide Source) , a different E.Coli probiotic, may also have impact.

It also leads to a hypothesis that could be tested easily: MCAS is associated with lower or non-existent levels of gram-negative bacteria in the microbiome.

CAUTION: What is claimed to be in a probiotic may not be

This is a long standing problem with commercial probiotics — there is no effective regulation that what is advertised is actually in the bottle. In this case, we want specific species — ideally just those species.

My family’s usual source is Custom Probiotics – because their products have no filler, single species usually, and single strains. Unfortunately, they only sell one of these species: Lactobacillus Acidophilus with a recommended adult dosage of 160 BCFU/day. A list of commercial probiotics with claimed species is here, unfortunately L.H. is almost always in mixtures except for one UK source, Metabolics, species LMG 26307 (they also sell Lactobacillus Acidophilus, species LMG 8151) so an ideal single source for a MCAS person in the EU who wish to trial these suggestions.

If you an “off the shelf” probiotic mixture, your odds are better of actually getting the right species when the probiotic does not just say “lactobacillus helveticus” but gives a strain, i.e. one of these: ATCC:15009,  CCUG:30139,  CIP:103146,  DSM:20075 , IFO:15019, JCM:1120,  BCCM/LMG:13555,  BCCM/LMG:6413,  NBRC:15019,  NRRL:B-4526,  CGMCC:1.1877. It is available from manufacturers, i.e. creative enzymes.

• “A new study by scientists at the University of California has found that contents of many bifidobacteria probiotic products differ from the ingredients listed….16 products.. only one matched the ingredient list .. Some products also contained non-label species” [Source 2015] 
• “Current trademark law and the lack of stringent regulation of probiotic manufacturing mean that the trademark owner can commercialize any formulation under the same brand, even if significantly different from the original.” The Unregulated Probiotic Market
• My earlier post: Deceptive Probiotic Labels

Genome Sequence of Lactobacillus helveticus, an Organism Distinguished by Selective Gene Loss and Insertion Sequence Element Expansion tells how unique this species is.

YouTube on the process used

I have done prior posts on POTS (POTS Revisited) and been requested to check the latest research. Checking PUBMED statistics, we see there have been many papers in the last few years

• “The physiology underlying “brain fog” in the absence of orthostatic stress in postural tachycardia syndrome (POTS) remains poorly understood. … greater slowing in psychomotor speed and a greater increase in symptom scores at study completion in the patients with POTS, including increased difficulty with concentration. All other physiologic responses (blood pressure and end-tidal carbon dioxide) did not differ between groups after PCST ” [2020]
• Restless legs syndrome is increased in postural orthostatic tachycardia syndrome [2020]
• Dry Eye Syndrome and Sicca Complex are Commonly Found in Patients with Postural Orthostatic Tachycardia Syndrome [2020]
• Mechanisms and management of gastrointestinal symptoms in postural orthostatic tachycardia syndrome [2020]
• Treatment of Postural Orthostatic Tachycardia Syndrome With Medication: A Systematic Review [2020] “Postural orthostatic tachycardia syndrome has been recognized for decades, but treatment is largely based on anecdotal experience and expert opinion. Pharmacologic treatment is inconsistent and unstandardized. …There is a paucity [very few] of high-quality data about effectiveness of medication in the treatment of postural orthostatic tachycardia syndrome. “

Trying Citizen Science

We have 55 samples annotated with POTS and we recently added enzymes to the system. Time to go on a statistical fishing expedition… and we found some fish, all of them small one (i.e. too low production)

EnzymeName	POTS Average	No POTS Average	Test Statistic	Obs
crotonobetainyl-CoA reductase	174	1500	-5.31511	28
L-carnitine CoA-transferase	177	1381	-5.04204	31
D-apionate oxidoisomerase	573	1541	-4.57861	29
nitrite reductase (NO-forming)	5311	17941	-4.46254	51
5-aminopentanamidase	5900	16862	-4.31631	51
phosphatidyl-myo-inositol alpha-mannosyltransferase	5523	17379	-4.16094	50
cysteinylglycine-S-conjugate dipeptidase	5611	17868	-4.15823	48
polyphosphate—glucose phosphotransferase	5621	17638	-4.09764	48
8-oxo-dGDP phosphatase	5725	17788	-4.05173	47
8-oxo-(d)GTP phosphatase	5930	17351	-3.93432	48
lactocepin	1411	8104	-3.90514	50
formyl-CoA transferase	5998	17156	-3.84911	46
oxalyl-CoA decarboxylase	6234	18799	-3.80263	39
galactofuranosylgalactofuranosylrhamnosyl-N-acetylglucosaminyl-diphospho-decaprenol beta-1,5/1,6-galactofuranosyltransferase	5714	14910	-3.60734	50
lipid II isoglutaminyl synthase (glutamine-hydrolysing)	8292	22101	-3.5937	54
galactan exo-1,6-beta-galactobiohydrolase (non-reducing end)	6876	19457	-3.53129	35
N-acetylhexosamine 1-kinase	6876	19434	-3.52637	35
dehydrogluconokinase	6710	18931	-3.52007	36
Pup amidohydrolase	5718	15393	-3.51166	47
prokaryotic ubiquitin-like protein ligase	5718	15393	-3.51166	47
all-trans-retinol dehydrogenase (NAD+)	6484	17326	-3.47966	41
gamma-glutamyl hercynylcysteine S-oxide hydrolase	6876	19217	-3.47867	35
glucosyl-3-phosphoglycerate phosphatase	7804	18811	-3.474	50
isopenicillin-N epimerase	6367	17710	-3.44546	38
2-acetylphloroglucinol acetyltransferase	6295	15991	-3.43971	45
phosphatidylinositol dimannoside acyltransferase	8899	20502	-3.38033	50
dolichyl-phosphate-mannose—protein mannosyltransferase	8156	17812	-3.34246	54
sorbose reductase	6144	15938	-3.29349	41
tRNA (adenine57-N1/adenine58-N1)-methyltransferase	8093	18743	-3.26853	48
tRNA (adenine58-N1)-methyltransferase	8093	18743	-3.26853	48

This is actually a happy path because for too low, we can identify probiotics that produces these missing enzymes. Three bifidobacterium are at the top of the list. Custom Probiotics daily recommended dosage for these are 350-400 BCFU /day.

bacillus pumilus	8
bacillus simplex	2
bacillus velezensis	8
bifidobacterium adolescentis	26
bifidobacterium animalis subsp. lactis bb-12	26
bifidobacterium longum	26
clostridium beijerinckii	5
clostridium butyricum	5
enterococcus durans	1
enterococcus faecalis	1
lactobacillus acidophilus	4
lactobacillus helveticus	4
lactobacillus kefiri	2
lactobacillus paracasei	2
lactobacillus plantarum	1
lactobacillus rhamnosus (strain atcc 53103 / gg)	2
lactobacillus salivarius	2
lactococcus lactis	3
leuconostoc lactis	2
streptococcus thermophilus	3

Bottom Line

We have deduced which probiotics should help POTS (if taken in sufficient dosage) by using citizen science on the annotated-with-symptoms uploads, the KEGG Enzyme data and statistics. We may not know the why’s of these enzymes missing causing POTS, but we have some ideas of where to start looking for explanations. Until then, we at least know what to try.

There have been NO STUDIES using Bifidobacterium probiotics with POTS published.

Again consult with your medical professional first.

This person has an interesting set of symptoms for ME/CFS. 40 yo male. I am following the same pattern as the two previous analysis. Every ME/CFS person share some factors and are different in other factors. There is nothing that works for all ME/CFS people.

• Symptoms
  • Depression
  • Irritability
  • Brain fog
  • Post exercise malaise
  • Tinnitus
  • Post nasal drip
  • Stuffy nose
  • Cold extremities & insensitivity to cold
  • Fragmented sleep
  • Low libido
  • Low appetite
  • Frequent bowel movements
• I’ve had different tests and bloodwork done over the years and these were the common outliers:
  • Low DHEA-s
  • Very high B12
  • High Vitamin D despite not supplementing
  • Low Estradiol (E2)
  • Mild blood coagulation
  • High(ish) eosinophils% (~5%)

Looking at Naive Predicted Symptoms From Bacteria table, we have:

Enzyme Analysis

The awesome results in a past post on an autism child, where the enzymes were identified as coming from bacteria species constantly reported as high with Autism, is causing me to look at enzymes shifts as a good strategy to identify the key bacteria to look at.

So the next step is to look for probiotics that can also produce these enzymes.

The easiest combination to obtain retail from the above are clostridium butyricum (Miyarisan ) which produces all 5 enzymes! or any of bifidobacterium adolescentis, bifidobacterium animalis subsp. lactis bb-12, and bifidobacterium longum. The latter ones (without additives) are available at Custom Probiotics (with a recommended daily dosage of 320-400 BCFU/daily) at the lowest cost per BCFU that I have seen.

KEGG Module Analysis

This is another way to evaluate the functions of the bacteria in a microbiome sample. There are less items then with Enzymes and, to be honest, I have not examined the results much after adding the code and data to compute them. There was nothing there.

End Product Outliers

Nothing was found outside of the ranges, and looking at Core Supplements there was one item of concern, high d-lactate production. High D-lactate is associated with neurological issues. (See these posts: Killing Lactobacillus to improve Brain Fog, Approaches to D-Lactic Acidosis). We also see that the microbiome suggests high B-12 (at 76%ile) which the labs report.

Unlike my last post on an autism child, there were no high enzymes to indicate the troublesome bacteria.

We turn to the Advance Suggestion engine and apply some filters.

Pass 1 for suggestions

First from Citizen Science we look at filtering for neurological decision making and drive a blank until we widen the search as shown below

Looking at the suggestions, we only find one item in common with the prior ME/CFS person: inulin (prebiotic).

Top probiotics suggestions all contain  saccharomyces boulardii. Flavonoids are a short list

• Barley, hulled – Weight: 0.98
• Barley, whole grain flour – Weight: 0.98
• Walnut – Weight: 0.98

This is close to my usual breakfast for many months: Barley porridge with walnuts!

Pass 2 for suggestions

We change the filtering to CFS/ME and drop back to the most extreme 3% – where we get results

We have a conflict on triphala. One subset of bacteria says to use it, a different subset says not to use it. Given that it’s the highest value in both cases we need to do an experiment. I would advocate doing triphala for 4-6 weeks to see if it improves neurological issues, then stop it and re-evaluate.

We have a long list of probiotics, all with appropriately the same value

Bottom Line

Remember this is strictly on the basis of the microbiome and our current state of knowledge in interpreting and being able to act on it. It is important not to view microbiome analysis as a magic silver bullet. A summary of suggestions to discuss with your medical professional.

• Probiotics
  • lactobacillus plantarum (probiotics)
  • At least one of bifidobacterium adolescentis, bifidobacterium animalis subsp. lactis bb-12, and bifidobacterium longum.
  • saccharomyces boulardii.
• Foods
  • Trial on triphala
  • Barley (and oats?) – note this would be deemed low or no gluten by some people
  • Walnuts
  • Inulin
• For brain fog issues (see earlier links)
  • berberine
  • neem
  • enterococcus faecium (probiotic)
  • miyarisan (clostridium-butyricum)
  • 100 mg every 12 hours of Thiamine (Vitamin B1) 
  • Acetylcysteine (NAC),
• For low-grade coagulation, See
  • Coagulation: Thick Blood Supplements for CFS )

In summary, clinical studies have tested some substances on various conditions which have been reported on PubMed. Microbiome analysis is based on microbiome shifts reported on PubMed by consuming some substances (ignoring medical conditions usually). If you construct a full list of both sets of substances, you will likely have only 10-20% of the substances in common. What has been studied in one context, has not been studied in the other context. Microbiome analysis is complimentary, not a replacement.

As always, to be reviewed with your medical professional before starting. There are algorithm/artificial intelligence generated suggestion based on data that has been entered (usually from gold standard sources).

Postscript on High Vitamin D

See these posts:

• Vitamin 25D and 1,25D measure – one reduces symptoms and one indicates CFS state
• Vitamin D and the Microbiome
• Autoimmune and Vitamin 1,25D

Feed back from person

” Indeed very insightful! Strangely enough, walnuts, tea and inulin both made me feel better despite not knowing why and your analysis make a lot of sense.”

This person has an interesting set of symptoms for ME/CFS. 34 yo female

• Neurological
  • Visual agnosia (inability to interpret sensations and hence to recognize things, typically as a result of brain damage.)
  • Severe hyperphagia ( abnormally strong sensation of hunger or desire to eat often leading)
  • Severe sleep circadian rhythm disturbance (only thing it responded to shortly was methylated Bs)
  • social anxiety (was severe now mild)
  • brain fog 
  • intermittent prosopagnosia ( the inability to recognize the faces of familiar people)
  • sensory overload – can’t stand showers, need darker room often

• Many of the above responds in some way to antibiotics 
• Official Diagnosis: autonomic/small fiber neuropathy, POTS, Hashimoto and now Sjogrens sicca with swollen parotids.

The positive response to antibiotics suggests that the microbiome pays a significant factor.

Looking at Naive Predicted Symptoms From Bacteria table, we have:

For predicted medical conditions from PubMed studies, we had one good match, Hay Fever — and for that it was due to no Clostridium butyricum being found. Note that bacteria because it reoccurs as an issue using an entirely different analysis path.

Enzyme Analysis

The awesome results in my last post on an autism child, where the enzymes were identified as coming from bacteria species constantly reported as high with Autism, is causing me to look at enzymes shifts as a good strategy to identify the key bacteria to look at.

So the next step is to look for probiotics that can also produce these enzymes.

The easiest combination to obtain retail from the above are clostridium butyricum (Miyarisan ) which produces all 11 enzymes! and streptococcus thermophilus (which produces 10/11) and is available without other things at Custom Probiotics (with a recommended daily dosage of 320 BCFU). Miyarisan is cited in my 2017 post, What is the ideal probiotic for CFS / IBS / FM patients? As always, start with a low dosage and increase to a therapeutic dosage (typically 3x the normal dosage) after consulting with your medical professional.

Note that the prior analysis of a ME/CFS person’s microbiome also have these two probiotics being the first choice.

• Probiotic Streptococcus thermophilus FP4 and Bifidobacterium breve BR03 Supplementation Attenuates Performance and Range-of-Motion Decrements Following Muscle Damaging Exercise
• Other studies used streptococcus thermophilus with other bacteria and found neurological improvements.

KEGG Module Analysis

This is another way to evaluate the functions of the bacteria in a microbiome sample. There are less items then with Enzymes and, to be honest, I have not examined the results much after adding the code and data to compute them. So here goes….

The first item above is associated with Vitamin C (Ascorbate) and influences gene expression [2018]. Looking at the chart below, I notice that H2O2 (hydrogen peroxide) is associated with it. Hydrogen peroxide is a major player for controlling some bacteria. It also feeds the Pentose phosphate pathway which cites “The PPP is one of the three main ways the body creates molecules with reducing power, accounting for approximately 60% of NADPH production in human”

Unfortunately, none of the bacteria producing this exist as probiotics.

End Product Outliers

Nothing was found outside of the ranges, but looking at Core Supplements there are two suggestions (low values, i.e. between 3 and 10ile%) Vitamin D, DAO Producing (diamine oxidase) with Cobalamin (Vitamin B12) and Gamma-Amino butyric acid (GABA) sitting around 15%ile. These are commonly used with ME/CFS and helpful to many. Because this person has cognitive issues, I did a little research on possible dosages.

• Suggested Dosages (should be reviewed with your medical professional)
  • Vitamin D: See this post for calculation, I suspect 10-15,000 IU/day
  • Cobalamin (Vitamin B12): 2000 μg/day
    •  One trial used 2000 μg/day vitamin B₁₂ and demonstrated a mean difference of 680 pg/mL (95% confidence interval 392.7 to 967.3) in favour of oral vitamin B₁₂ [2018]
  • GABA: 300 mg /day (2018)
    • [Gamma-aminobutyric acid–metabolism and its disorders].“stiff-person syndrome, chronic fatigue syndrome, anxiety disorders and seizures”
    • Brain Fog association (sub-clinical hypercoagulation):
      • [The effect of various doses of gamma-aminobutyric acid, adrenaline and insulin on coagulation time, prothrombin time and the prothromboplastic activity of rat blood]
      • Effect of GABA derivatives on the rate of thrombus formation, platelet aggregation, and plasma coagulation capacity in rats with experimental gestosis
      • Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review [2020]
  • DAO: Nothing dosage specific, people that I know who uses it, does it on an in-need basis.
    • “Histamine intolerance, also referred to as enteral histaminosis or sensitivity to dietary histamine, can be defined as a disorder arising from reduced histamine degradation capacity in the intestine due to impaired DAO activity, leading to its accumulation in plasma and the appearance of adverse effects [11,41,55].”

The above are compensating items that should be taken daily (or broken in every 8-12 hrs) which attempts to create a more healthy/normal environment for the rest of the microbiome and body to be living in. They are symptom relief and likely not cause relief — which takes us to the next step: Clostridium butyricum:

Unlike my last post on an autism child, there were no high enzymes to indicate the troublesome bacteria.

We turn to the Advance Suggestion engine and apply some filters.

Pass 1 for suggestions

First from Citizen Science we look at filtering for neurological decision making and drive a blank until we widen the search as shown below

Flavonoid Foods (Most important first): Pomegranate, Apples, Nuts, almonds ,Coconut (and water), Bananas, Cinnamon, and Dates, deglet noor 

Pass 2 for suggestions

We change the filtering to CFS/ME and drop back to the most extreme 3% – where we get results

Flavonoid Foods was similar to above, but apples and banana were dropped off.

Bottom Line

Remember this is strictly on the basis of the microbiome and our current state of knowledge in interpreting and being able to act on it. It is important not to view this as a magic silver bullet. This person has some symptoms where the existing medical literature has suggestions (and which I have done posts summarizing and cited sources for ME/CFS) including the following:

• Bacopa monniera and Cognitive Function (we have no information on this supplement impact on the microbiome)
• Intrinsic Factor and low Vitamin B-12 levels Cognitive Impact
• The Neuroprotectors: Remember your super heroes for cognitive issues!
• Dry Eye Disease (Sjogren)/Syndrome – where suggestions include, Bioferim S (containing 2 of the probiotics suggested above)
• CFS: Insomnia and Sleep Disturbance
• Anxiety and the Microbiome
• POTS Revisited
• Microbiome Site Update – POTS and ALA
• and this older decision chart A decision chart for biohacking M.E. et al and What is comorbid with CFS/FM 

In summary, clinical studies have tested some substances on various conditions which have been reported on PubMed. Microbiome analysis is based on microbiome shifts reported on PubMed by consuming some substances (ignoring medical conditions usually). If you construct a full list of both sets of substances, you will likely have only 10-20% of the substances in common. What has been studies in one context, has not been studied in the other context. Microbiome analysis is complimentary, not a replacement.

From the Microbiome

We have two set of items from above

• Items that will compensate for existing issues with enzymes and end product production (symptom relief)
  • Miyarisan, Vitamin D, DAO Producing (diamine oxidase), Cobalamin (Vitamin B12), Gamma-Amino butyric acid (GABA), streptococcus thermophilus

• Items that will help shift the microbiome to a better state (fixing the root problem) – this is based on one of dozens of possible filtering of bacteria into subsets.
  • Number 1 item is Cocoa — as in 85% – 92% Chocolate daily (or more often)… a rough prescription
  • Several different probiotics (if you get a mixture — make sure that it is on the positive list. Some species of probiotics will make things worse for some people).

Oops — we forgot antibiotics

This user had improvement on antibiotics, so which ones are suggested? Back to the suggestion page and checking/unchecking items.

And more important, which ones to avoid!

As always, to be reviewed with your medical professional before starting. There are algorithm/artificial intelligence generated suggestion based on data that has been entered (usually from gold standard sources).