The problem with “normal ranges” from Labs

I have a M.Sc. in Statistics and roll my eyes with the ranges being given by most commercial labs. I know precisely the process that most are rote-following:

To set the normal range, take samples from a group of people with no known issues. Compute their average and standard deviation. Abnormally low is average – 1.95 standard deviations and abnormally high is average plus 1.95 standard deviations.

Other approaches use just 40 people with the values of the 2.5%ile and 97.5%ile being used. Unfortunately, with 40 people that becomes the lowest value and the highest value. At both ends, that is a volatile number ­čÖü

My goal with MicrobiomePrescription is to show the numbers from over a thousand samples and let people determine if the numbers are actually unusual by visual inspection.

What should be seen is illustrated below. The average line should be close to the 50%ile with this large of a sample. Two views are usually best.

The log view will give a straight line usually. Where it is not straight, we may have a problem. In this case, below 10%ile is suspect, below 5% is suspect. Over 92%ile is also suspect.
Looking at actual numbers or percentage, gives you better numbers. A typical range is from 35% to 72%

Atypical Bacteria

This bacteria is only reported by one lab, Thryve Inside. If is actually is a sibling to Bifidobacteria genus, both are children of Bifidobacteriaceae.

For another bacteria, we have the average a long distance from the 50%ile and we see what looks like three patterns — each with their own straight line (and not one like above). To get the true 50%ile (including those with zero count) it’s (50+38.2)/(100+38.32 [for Zeros]) = 63%ile on the chart.

The apparent area of concern is the 50%ile above, and issue may be 60%ile
Translating to percentage, Over 0.3% may indicate atypical amounts.

Is it bad to be atypical? If there is not a medical condition or illness associated with it, then likely not. Variety is the spice of life, and the reality of the microbiome.

Some Extreme Examples

For this bacteria, having the average or higher is suspect, factoring in the zeros, we have the average actually being the (82+40)/(100+40) = 87%ile. Visually you can see that things are not looking good.

Bottom Line

Bacteria have a wide variety of growth patterns. Without inspect of the distributions and related information, you may either assume that there is no problem (because the lab ranges are poor — a false positive), or there is a problem when you may have 40% of people have less or more than you (– a false negative).

Do not expect labs to look at the distributions — they only have time to print the numbers and give a canned interpretation. For the microbiome, a canned interpretation is dangerous because of the impact of diet can have. I have oatmeal for breakfast every day, dark 100% rye sandwich for lunch, indian food with chicken for supper. I am pretty much wheat free… and that absence will shift my microbiome greatly.

You have to look at them yourself. You can look up most bacteria reported by labs at this URL: https://microbiomeprescription.com/Library/Lookup

Drill down into Irritable Bowel Syndrome

I am reasonably complete in updating the database. If you know of any substances not shown below that have published peer review studies (a.k.a. PubMed) please email me with links so I may update it.

IBS is often concurrent with ME/CFS and FM.

The drill down page requires you to login. Which means nothing more than going to the login page, enter your email and wait for a login link to arrive in your email. The page is below for those who do not wish to login … my comments continue below it in “Review”

Irritable Bowel Syndrome

This list modifiers reported for specific conditions with links to studies.

Some of the items listed as improving may have inconsistent results from studies. It is recommended that the studies cited be review before considering any change.

ModifierImpactCitations
aloe veraCan cause/Worsen1
aloe veraImproves/Treats1
bacillus coagulans (probiotics)Improves/Treats8
bifidobacterium (probiotics)Improves/Treats1
Boswellia serrataImproves/Treats2
clostridium butyricum (probiotics)Improves/Treats4
enterococcus faecium (probiotic)Improves/Treats1
Human milk oligosaccharides (prebiotic, Holigos)Improves/Treats2
hypericin(St. John’s Wort)Can cause/Worsen1
lactobacillus plantarum (probiotics)Can cause/Worsen2
lactobacillus plantarum (probiotics)Improves/Treats2
lactobacillus rhamnosus gg (probiotics)Improves/Treats4
l-glutamineImproves/Treats1
low fodmap dietImproves/Treats13
mutaflor escherichia coli nissle 1917 (probiotics)Improves/Treats1
peppermint (spice, oil)Improves/Treats5
Prescript Assist (Original Formula)Improves/Treats2
rifaximin antibioticsImproves/Treats2
Serum-derived bovine immunoglobulin/protein isolateImproves/Treats4
symbioflor 2 e.coli probioticsImproves/Treats1
vitamin dImproves/Treats3
vsl#3 (probiotics)Improves/Treats5

Quantities from PubMed Studies on Irritable Bowel Syndrome

Show 30100200All entriesSearch:

DirectionSubstanceNotesSource
Improvesvitamin dsupplemented weekly with 50,000 IU Vitamin D improve the severity of symptoms and QOL in patients with IBSSource
Improvesvitamin doral vitamin D3 2000IU/day for 6 months can be effective in treating adolescents with IBS and vitamin D deficiencySource
Improvesvitamin d50 000 IU vitamin D3 The IBSSS and the IBS-QoL scores in the vitamin D group significantly improved comparedSource

Showing 1 to 3 of 3 entriesPrevious1Next

Bacteria shifts from Pub Studies

Click to get custom suggestions

Show 30100200All entriesSearch:

ObservedBacteria NameRankDocumentation
High LevelsActinobacteriaphylumCitation
High LevelsAkkermansia muciniphilaspeciesCitation
High LevelsBacillus aeruginosusspeciesCitation
High LevelsBacteroidaceaefamilyCitation
High LevelsBacteroidesgenusCitation
High LevelsBacteroidesgenusCitation
High LevelsBacteroides thetaiotaomicronspeciesCitation
High LevelsChristensenellaceaefamilyCitation
High LevelsClostridiaclassCitation
High LevelsClostridialesorderCitation
High LevelsDesulfovibriogenusCitation
High LevelsDesulfovibrionaceaefamilyCitation
High LevelsDialister invisusspeciesCitation
High LevelsEnterobactergenusCitation
High LevelsEnterobacteriaceaefamilyCitation
High LevelsEnterobacteriaceaefamilyCitation
High LevelsEnterococcusgenusCitation
High LevelsErysipelotrichaceaefamilyCitation
High LevelsEscherichia colispeciesCitation
High LevelsEscherichia colispeciesCitation
High LevelsFaecalitaleagenusCitation
High LevelsLachnospiraceaefamilyCitation
High LevelsMethanobrevibacter smithiispeciesCitation
High LevelsMycoplasma hominisspeciesCitation
High LevelsOscillospiraceaefamilyCitation
High LevelsPrevotellagenusCitation
High LevelsPrevotellagenusCitation
High LevelsPrevotellagenusCitation
High LevelsPrevotellagenusCitation
High LevelsPrevotellagenusCitation

Showing 1 to 30 of 74 entriesPrevious123Next

Bacteria shifts from Citizen Science

This is based on the machine learning implemented on this site. Unpublished results.

Click to get custom suggestions

ObservedBacteria NameRankRelative Strength
High LevelsEubacteriaceaefamily62
High LevelsEubacteriumgenus48
Low LevelsAkkermansiagenus105
Low LevelsBifidobacteriumgenus100
Low LevelsPseudobutyrivibriogenus77
Low LevelsSubdoligranulumgenus76
Low LevelsLactobacillusgenus72
Low LevelsAnaerotruncusgenus61
Low LevelsBlautiagenus60
Low LevelsCoriobacteriiaclass58
Low LevelsRoseburiagenus55
Low LevelsRoseburia faecisspecies55
Low LevelsAcidaminococcalesorder53
Low LevelsErysipelatoclostridiumgenus52
Low LevelsBacteroides thetaiotaomicronspecies51
Low LevelsFaecalibacteriumgenus51
Low LevelsPeptostreptococcaceaefamily45
Low LevelsVerrucomicrobiaceaefamily45
Low LevelsLachnospiraceaefamily44
Low LevelsDorea formicigeneransspecies44

Review

For citizen science looking at probiotics, we actually have a short list and a longer one from PubMed. Lactobacillus GG showed up on both, and on the actual studies list. Clostridium butyricum (probiotics) also has a match from PubMed bacteria to Actual Studies. Different oligosaccharides were on the take and avoid list. Unfortunately, most studies on IBS did not test differences (i.e. tested the forest and not the tree species).

From Citizen Science
From PubMed

On the avoid list was inulin and it’s associated jerusalem artichoke. Recommending that is a “pro-forma” suggestions from many physicians. So what gives? For that one I did find a study. The study results suggested that you should avoid it — a nice agreement.

 However, flatulence severity was improved by prebiotics at doses ÔëĄ6 g/d (SMD: -0.35; 95% CI: -0.71, 0.00; P = 0.05) and by non-inulin-type fructan prebiotics (SMD: -0.34; 95% CI: -0.66, -0.01; P = 0.04), while inulin-type fructans worsened flatulence (SMD: 0.85; 95% CI: 0.23, 1.47; P = 0.007).

Prebiotics in irritable bowel syndrome and other functional bowel disorders in adults: a systematic review and meta-analysis of randomized controlled trials 2019

Fibromyalgia lacks strong microbiome profile

I’ve just added Fibromyalgia to the website’s Special Summaries. Both published studies and citizen science fail to find any strong patterns. Today (remember the site is constantly being updated with new studies), we see the following summary. Obtaining only two bacteria from citizen science seems to make a strong statement that while the microbiome may be a contributing factor, it is unlikely to be causal.

I tend to favor the root cause being tissue hypoxia with the tissue generating pain from a lack of oxygen.

There may be multiple causes. One possible is coagulation products. Items like serrapetase, nattokinase and lumbrokinase may help. I could not locate any studies using these for FM.

Fibromyalgia

This list modifiers reported for specific conditions with links to studies.

Some of the items listed as improving may have inconsistent results from studies. It is recommended that the studies cited be review before considering any change.

ModifierImpactCitations
bifidobacterium bifidum (probiotics)Improves/Treats1
CoQ 10Improves/Treats2
d-riboseImproves/Treats1
ExerciseImproves/Treats1
fish oilImproves/Treats1
green teaImproves/Treats1
lactobacillus acidophilus (probiotics)Improves/Treats1
lactobacillus casei (probiotics)Improves/Treats1
lactobacillus rhamnosus gg (probiotics)Improves/Treats1
L-carnitineImproves/Treats1
low-pressure hyperbaric oxygenImproves/Treats1
magnesiumCan cause/Worsen1
magnesiumImproves/Treats7
melatonin supplementImproves/Treats1
mirtazapine (prescription)Improves/Treats3
PregabalinImproves/Treats2
SAM-eImproves/Treats1
Staphylococcus vaccineImproves/Treats1
trazodone hydrochloride (prescription)Improves/Treats2
TryptophanImproves/Treats2
vitamin dImproves/Treats4

Bacteria shifts from Pub Studies

ObservedBacteria NameRankDocumentation
High Levels[Clostridium] scindensspeciesCitation
High LevelsAlistipesgenusCitation
High LevelsAlistipes onderdonkiispeciesCitation
High LevelsBlautia hydrogenotrophicaspeciesCitation
High LevelsButyricicoccusgenusCitation
High LevelsDoreagenusCitation
High LevelsEisenbergiella tayispeciesCitation
High LevelsErysipelatoclostridium ramosumspeciesCitation
High LevelsFlavonifractor plautiispeciesCitation
High LevelsHungatella hathewayispeciesCitation
High LevelsIntestinimonas butyriciproducensspeciesCitation
High LevelsParabacteroides merdaespeciesCitation
High LevelsRoseburiagenusCitation
Low LevelsBacteroidesgenusCitation
Low LevelsBacteroides uniformisspeciesCitation
Low LevelsBifidobacteriumgenusCitation
Low LevelsBlautia faecisspeciesCitation
Low LevelsClostridiumgenusCitation
Low LevelsEubacteriumgenusCitation
Low LevelsFaecalibacterium prausnitziispeciesCitation
Low LevelsHaemophilus parainfluenzaespeciesCitation
Low LevelsLachnospiraceaefamilyCitation
Low LevelsLactobacillusgenusCitation
Low LevelsPrevotella coprispeciesCitation
Low LevelsRuminococcaceaefamilyCitation

Bacteria shifts from Citizen Science

This is based on the machine learning implemented on this site. Unpublished results.

ObservedBacteria NameRankRelative Strength
High LevelsBacteroides uniformisspecies6
High LevelsLactobacillaceaefamily2

filgotinib for ME/CFS and RA

A reader asked about this. It is a new drug waiting for approval in the EU. On a Spanish group, it is asserted that:

“This is very encouraging news for patients with ME/CFS, as this drug could show very promising results in this ailment. Specifically, this drug decreases levels of inflammatory cytokines, which are believed to be the main cause of symptoms.”

Unfortunately, there have not been a single study for ME/CFS and this statement is very speculative (in my days, I have seen literally dozens of similar claims which consistently under-delivered or caused additional problems). Wikipedia gives a good summary of what it is and its issues.

The most applicable study is shown below.

Bottom Line

Treatments for Rheumatoid Arthritis have often been tried and used for a subset of ME/CFS. Results were generally mixed. The goal should not be “decreases levels of inflammatory cytokines” but stopping the source of inflammatory cytokines. I believe the dominant source of inflammatory cytokines is a microbiome dysfunction.

You do not want to keep painting the walls to cover up water stains from a leaking roof; you want to fix the roof first.

HHV, Mycoplasma and Microbiome

A reader asked about what we know. They were looking for food for a child that may inhibit these by inhibiting the bacteria that provides them with the metabolites to flourish. These two have a high prevalence with ME/CFS.

We need to be aware that there may be a ‘mafia family’ in operation, for example: “HIV also acts synergistically with multiple other viruses, such as HPV, EBV, varicella zoster virus (VZV), and HHV-8.┬á” [2019]

Unfortunately available literature on PubMed contains few human studies.

  • Lower ┬áPrevotella,Mycoplasma pneumoniae, Staphylococcus epidermidis, and┬áStaphylococcus aureus┬á [2019]
An integrated respiratory microbial gene catalogue to better understand the microbial aetiology of Mycoplasma pneumoniae pneumonia [2019]

The reader had uploaded a microbiome from Thryve and I wanted to see how severe mycoplasma was:

The sample of concern placed them at the 8th percentile (very low). So mycoplasma is unlikely to the cause. 70% of Thryve reports had this group.

My intent was to see if there were any statistically significant association with other bacteria (friend or foe analysis).

Drilling down to the species level, we find that he numbers were not abnormal (below average but at median)

Concerning HHV virus — that is outside of the scope of my analysis site. There is no published literature to work from. I do have a personal belief that HHV and other virus reactivation is a side effect of microbiome dysfunction. Yes, some antivirals help — but those same antivirals also alter the microbiome leaving these antiviral mechanism of action unclear.

Returning to the person

  • The reader child “he still have learning disabilities”. I looked at Naive Predicted Symptoms with their microbiome and with a score of 1.0 (highest), we have these predicted that match this description (25 possible of 5200 pairs possible). HHV6 and Mycoplasma were included in the symptom list! (this does not mean the child has them — rather that people who were told or believed they had them; self reporting and not a lab test)
What is identified

I proceeded to pick the bacteria (clicking the checkboxes above) that matched these symptoms and built a custom profile. The result was that many bacteria recurred in different combinations, so we ended up with just 9.

Running it through the suggestions machine learning we got:

As often happens — some probiotics are good and other bad. A “good probiotic mixture” is often the wrong thing to take.
The recommended probiotics,,,

Bottom Line

The above are suggestions from a machine learning algorithm. They should be reviewed and discussed with your medical professional before starting.

The goal was to modify diet to help with the symptoms. We were not able to find anything based on the presumed cause in conventional medical literature. We were able to identify some specific bacteria shifts that corresponded to reported symptoms and get diet suggestions from those.