Fungi: Clavicipitaceae / Hypocreales / Sordariomycetes

Fungi and the microbiome finally got on my radar. Apologies to some, but there is a lot of different items on the microbiome radar screen.

“Small intestinal fungal overgrowth (SIFO)… Two recent studies showed that 26 % (24/94) and 25.3 % (38/150) of a series of patients with unexplained GI symptoms had SIFO. …. but evidence for eradication is lacking.”Small intestinal fungal overgrowth [2015]

As I did with taxa years ago, I will be writing a blog on each one reviewing the literature. If there is sufficient data at the end, I may add it as a feature to Microbiome Prescription. See also:

One of my reader’s results motivated this choice. The data from a Thorne Microbiome Test. Almost 17 out of 20 people have less of it. The person also has a Crohn’s diagnosis (with SIBO and IBS earlier).

Preventive for Fungi

The following are suggestions:

  • Reduce and keep your living space humidity at 50% or lower (typically done by dehumidifiers). EPA recommends 30-50% [EPA]; we set our dehumidifiers for 35%.

Moisture parameters and fungal communities associated with gypsum drywall in buildings [2015]

Remember, all fungi are not the same. Antibacterial and Antifungal Activities of Spices [2017] does not mention all fungi that I am reviewing. Additionally, some spices are known to have Fungal Contamination of some Common Spices [2022] and Fungi and aflatoxins associated with spices in the Sultanate of Oman [2002] which included cloves (often deem an antifungal).

Basic Information

Ergot alkaloids are highly diverse in structure, exhibit diverse effects on animals, and are produced by diverse fungi in the phylum Ascomycota, including pathogens and mutualistic symbionts of plants. These mycotoxins are best known from the fungal family Clavicipitaceae and are named for the ergot fungi that, through millennia, have contaminated grains and caused mass poisonings, with effects ranging from dry gangrene to convulsions and death. However, they are also useful sources of pharmaceuticals for a variety of medical purposes.

Ergot Alkaloids of the Family Clavicipitaceae [2017]

Bottom Line

This is an interesting fungi with little known ill-effects and some potential good effects for IBD and colitis. Thorne does not identify the genus leaving us with more uncertainty. With no clean human adverse effects (apart from Ergotism this is specific to some members of this family only).

There are two types of ergotism. The first is characterized by muscle spasms, fever and hallucinations and the victims may appear dazed, be unable to speak, become manic, or have other forms of paralysis or tremors, and suffer from hallucinations and other distorted perceptions.[16] This is caused by serotonergic stimulation of the central nervous system by some of the alkaloids.[16] The second type of ergotism is marked by violent burning, absent peripheral pulses and shooting pain of the poorly vascularized distal organs, such as the fingers and toes,[16] and are caused by effects of ergot alkaloids on the vascular system due to vasoconstriction, sometimes leading to gangrene and loss of limbs due to severely restricted blood circulation.

Wikipedia

Unless there are symptoms of ergotism, I would suggest ignoring it. Some genus may do good and other may do harm. We lack sufficient information and I do not advocate taking action without evidence to warrant it.

Fungi: Exophiala / Herpotrichiellaceae / Chaetothyriales

Fungi and the microbiome finally got on my radar. Apologies to some, but there is a lot of different items on the microbiome radar screen.

“Small intestinal fungal overgrowth (SIFO)… Two recent studies showed that 26 % (24/94) and 25.3 % (38/150) of a series of patients with unexplained GI symptoms had SIFO. …. but evidence for eradication is lacking.”Small intestinal fungal overgrowth [2015]

As I did with taxa years ago, I will be writing a blog on each one reviewing the literature. If there is sufficient data at the end, I may add it as a feature to Microbiome Prescription.

One of my reader’s results motivated this choice. The data from a Thorne Microbiome Test. Almost 9 out of 10 people have less of it. The person also has a Crohn’s diagnosis.

Preventive for Fungi

The following are suggestions:

  • Reduce and keep your living space humidity at 50% or lower (typically done by dehumidifiers). EPA recommends 30-50% [EPA]; we set our dehumidifiers for 35%.

Moisture parameters and fungal communities associated with gypsum drywall in buildings [2015]

Remember, all fungi are not the same. Antibacterial and Antifungal Activities of Spices [2017] does not mention this fungi. Additionally, some spices are known to have Fungal Contamination of some Common Spices [2022] and Fungi and aflatoxins associated with spices in the Sultanate of Oman [2002] which included cloves (often deem an antifungal).

Basic Information

Image from [Mycology]

It is sometime identified as  black yeast fungus.

Treatment

Cleaning Dishwashers etc

The conventional advice is to use vinegar,baking soda or bleach. Studies indicate that it tolerates a very wide variety of pH (Roles of the pH signaling transcription factor PacC in Wangiella (Exophialadermatitidis [2009] ), i.e. pH 2.5 to pH 8 with most effective to inhibit being pH 2.5 (where Vinegar is). Bleach is pH 11-13, so likely also effective.

Since this often is black in appearance, sinks and other places should be regularly checked for any black discoloring which could indicate mold..

Bottom Line

This attempts to summarize the current information on Exophiala.

Fungi: Malassezia / Malasseziaceae / Malasseziales / Malasseziomycetes / Basidiomycota

Fungi and the microbiome finally got on my radar. Apologies to some, but there is a lot of different items on the microbiome radar screen.

“Small intestinal fungal overgrowth (SIFO)… Two recent studies showed that 26 % (24/94) and 25.3 % (38/150) of a series of patients with unexplained GI symptoms had SIFO. …. but evidence for eradication is lacking.”

Small intestinal fungal overgrowth [2015]

As I did with taxa years ago, I will be writing a blog on each one reviewing the literature. If there is sufficient data at the end, I may add it as a feature to Microbiome Prescription.

One of my reader’s results motivated review using Xenogene (ES) and Thorne (USA) reports that have been shared. The data from a shotgun test by Thorne had this being the highest fungi. They reported the percentile ranking of over 90%ile (i.e. 9 of 10 people who has this fungi, has less). This was their highest percentile and of concern is that this specific fungi is associated with Crohn’s disease which they have (as does 26 other people who have spared their microbiome test results).

Basic Information

ProductFormulationInstructionEvidence level and strength of recommendationReference
Systemic treatment
Itraconazole200 mg daily up to 3 weeksA I-ii(77, 78)
Fluconazole100–200 mg daily for 1–4 weeksB III(79, 80)
Fluconazole300 mg once weekly for 1–2 monthsB IV(82)
IsotretinoinDosed as in the treatment of acneC III(81)
From Evidence-based Danish Guidelines for the Treatment of Malassezia-related Skin Diseases [2015]

In terms of non-prescription items:

Antifungal activity of herbal extracts against Malassezia species[2015] lists

  • nettle leaves (Urtica dioica),
  • colocynths fruits (Citrullus colocynthis),
  • green tea (Camellia sinensis),
  • burdock root (Arctium lappa) extracts

Anti-Malassezia furfur activity of Several Medicinal Herb [2019]

  • Cinnamomum cassia – Best: a.k.a. Chinese cinnamon,
  • Rhus javanica (next): a.k.a. Chinese Sumac
    “Rhus javanica Linn, a traditional medicinal herb from the family Anacardiaceae, has been used in the treatment of liver diseases, cancer, parasitic infections, malaria and respiratory diseases in China, Korea and other Asian countries for centuries.” [2015]

Inhibitory effect of plant essential oils on Malassezia strains from Iranian dermatitis patients [2018] reports (in decreasing order):

  • Cuminum cyminum [Cumin]
  • Lavandula stoechas [Spanish Lavender]
  • Artemisia sieberi [the desert worm wood]

More on Crohn’s Disease

” The mycobiota of CD patients were characterized by an expansion of Malassezia and a depletion of Saccharomyces, along with increased abundances of Candida albicans and Malassezia restrictaMalassezia was associated with the need for treatment escalation during follow-up”

The ileal fungal microbiota is altered in Crohn’s disease and is associated with the disease course [2022]

“The two patients whose IBD was active at the time of initiation of treatment had complete clinical and endoscopic response after 6 and 9 months of itraconazole treatment respectively …they were able to withdraw immunosuppression and anti-TNF-α therapy during the entire itraconazole treatment course and the time to relapse in two of the Crohn’s patients was at least 10 months post-itraconazole therapy

The effects of itraconazole on inflammatory bowel disease activity in patients treated for histoplasmosis [2010]

The Montreal Heart Institute[2022] is sponsoring a clinical trail on terbinafine and itraconazole to treat Crohn’s Disease.[Website][WHO Trial Information]

Bottom Line

This attempts to summarize the current information on Malasseziaceae.

Preventive for Fungi

The following are suggestions:

  • Reduce and keep your living space humidity at 50% or lower (typically done by dehumidifiers). EPA recommends 30-50% [EPA]; we set our dehumidifiers for 35%.

Moisture parameters and fungal communities associated with gypsum drywall in buildings [2015]

Remember, all fungi are not the same. Antibacterial and Antifungal Activities of Spices [2017] does not mention this fungi. Additionally, some spices are known to have Fungal Contamination of some Common Spices [2022] and Fungi and aflatoxins associated with spices in the Sultanate of Oman [2002] which included cloves (often deem an antifungal).

Symptoms/Diagnosis association to Bacteria

This is a continuation of Bacteria interacting with Bacteria thread looking at proforma analysis methods and suggesting better processes. My orientation in clinical treatment. When I read a paper such as the one quote below, I roll my eyes. We know Bifidobacterium is less but how much less is needed in an individual sample is unanswered. Similarly which strains or species are shifted is unanswered.

We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. 

Gut microbiome alterations in Alzheimer`s disease. Scientific reports (Sci Rep ) Vol: 7 Issue 1 Pages: 13537
Pub: 2017 Oct 19 Epub: 2017 Oct 19 

This is the reality for hundreds of papers listed here.

I run a citizen science site where many people(2100+) have uploaded their samples (5200+ – usually 16s) and a significant number(1900+) have annotated their samples with symptoms. Walking down the same Chi2 path as I did with bacteria, we get some potentially interesting insights. I am a statistician by training and work experience.

General Approach

We look at the number of bacteria with low/high bacteria with a specific symptom (say 300 reports) and compare it to others. What others is can be one of the following:

  • Those reporting symptoms but not this symptoms (leaving 1600 samples)
  • All people without this symptoms (leaving 4900 samples).

My experience is that having significantly more samples results in higher Chi2 values despite the others including some with the symptoms. Conceptually, we may have a lower Chi2 value because of this.

For our example symptoms, Neurological-Audio: Tinnitus (ringing in ear) with 433 samples with this annotation. The table below shows the average percentile ranking.

Tax NameTax rankTinnitus
Mean
Others
Mean
unclassified Herbaspirillumnorank50.322.6
Lacrimispora saccharolyticaspecies78.153.1
unclassified Sutterellanorank31.152.6
Collinsella tanakaeispecies60.143.0
Prevotella paludivivensspecies32.948.7
Proteusgenus61.646.0
Desulfonatronovibriogenus54.238.8
Tepidimicrobium xylanilyticumspecies62.347.1
Prevotella oralisspecies37.752.5
Bifidobacterium gallicumspecies33.147.9
Bifidobacterium adolescentisspecies36.748.8

We are going to use Bifidobacterium gallicum (NCBI 78342) because of the number of samples(1400+) reporting it. What we got is below. From this we can infer odds such as:

  • Below 22%ile levels is a double the risk of having Tinnitus
  • Below 9%ile levels is four times the risk of having Tinnitus
PercentileExpectedObsChi2
10.7913190.6
97.112974.1
107.93068.7
2217.384037.7
3124.494524.9
3628.444923.2
4737.13519.8
4938.71528.9
5039.5539.2
5140.29549.5
5241.08559.8
5341.875610.1
5442.665812.0
5543.456014.0
5644.246114.4
6248.98629.1
6349.77639.5
6450.566511.5
6853.72668.8
6954.51667.8
7156.09677.3
7256.88687.8
7357.67698.2
7559.25719.3
7861.62727.9
7962.417410.2
8667.94755.2
9171.89762.6
9373.47772.4
9675.84781.5
9978.21790.8

Looking at a bacteria that is available as a probiotics, Bifidobacterium adolescentis (NCBI 1680) and plotting the Chi2 against the percentiles we find that the probability of having Tinnitus has a threshold around 70%ile, or in percentage terms 0.43% of the microbiome. Y axis is Chi2, X axis is the percentile of others.

Each of the above taxa are contributor to the risk of Tinnitus without any being the single cause.

We have 79 of 433 samples annotated with Tinnitus (18.2%) having Bifidobacterium adolescentis. With non Tinnitus we have 2395 out of 4800 samples (49.9%) having Bifidobacterium adolescentis suggesting that not having Bifidobacterium adolescentis is a significant risk factor for developing Tinnitus.

Other Candidate Probiotics

Tinnitus
Mean
Others
Mean
Tinnitus
Frequency
Other
Frequency
Bifidobacterium pseudocatenulatum
NCBI 28026
53.645.28%7%
Bifidobacterium dentium
NCBI 1689
554514%20%
Bifidobacterium catenulatum
NCBI1686
24.643.812%23%
Limosilactobacillus fermentum
NCBI 1613
51.942.512%10%
Bifidobacterium kashiwanohense PV20-2
NCBI 1447716
31.445.19%20%
Bifidobacterium catenulatum subsp. kashiwanohense
NCBI 630129
334511%21%
Ligilactobacillus NCBI 276788737.94911%14%

Digging Deeper

We have a well studied taxa as a key candidate, Bifidobacterium adolescentis. Let us look at this 2022 article, The Role of Gut Dysbiosis in the Pathophysiology of Tinnitus: A Literature Review (tinnitusjournal.com) which cites “It has been previously described that the presence of tinnitus is related to the decrease in inhibitory neurotransmitters such as GABA and an increase in excitatory neurotransmitters. Besides, the increased GABAergic inhibitory neurons and decreased excitatory responses have been successfully reported to prevent tinnitus, proving the role of neurotransmitter modulation in tinnitus.”

We then find related studies:

This suggests that an appropriate clinical trail of a Bifidobacterium adolescentis that is both human sourced and a high GABA producer should be done. Ideally with good persistence probability. A further key factor is to determine the pH value for people with tinnitus since studies have shown that the amount of GABA production is deeply influenced by the pH.

We have a lots of other taxa to investigate.

Bottom Line

Using Chi2 and percentiles of samples seem to be different sides of the same coin. The information gleamed from using this approach may often have direct clinical consequences, i.e. for Tinnitus, taking Bifidobacterium adolescentis probiotics and making diet changes to support this bacteria.

The key aspect of this post is not Tinnitus but methodology. From existing data, a lot more items with statistical significance can be extracted.

Possible Bacteria Connected to Salicylate Sensitivity

We have a small number of samples annotated with this condition. From this our candidate bacteria are shown below. Almost all of the significant ones are excess counts.

Tax_NameTax_rankSympMean
Hathewaya histolyticaspeciesToo many
Sedimentibacter hydroxybenzoicusspeciesToo many
Peptococcus nigerspeciesToo many
AlcaligenaceaefamilyToo many
Blautia coccoidesspeciesToo many
Caloramator fervidusspeciesToo many
SedimentibactergenusToo many
CatonellagenusToo many
Blautia productaspeciesToo many
Coprobacillus cateniformisspeciesToo many
Blautia gluceraseaspeciesToo many
Catonella morbispeciesToo many
MediterraneibactergenusToo many
Bacillales Family X. Incertae SedisfamilyToo many
CoprobacillusgenusToo many
OscillospiragenusToo many
CollinsellagenusToo few
AcetobacteriumgenusToo many
Blautia hanseniispeciesToo many
PedobactergenusToo many
Faecalibacterium prausnitziispeciesToo few
FaecalibacteriumgenusToo few
MycoplasmataceaefamilyToo many
Johnsonella ignavaspeciesToo many
Bacteroides cellulosilyticusspeciesToo many
MycoplasmatalesorderToo many
JohnsonellagenusToo many
AnaerofilumgenusToo many
XanthomonadalesorderToo many
ChromatialesorderToo many
RuminococcusgenusToo many
PeptococcusgenusToo many
Tissierellia incertae sedisnorankToo many
Anaerotruncus colihominisspeciesToo many
HathewayagenusToo many
Blautia schinkiispeciesToo many

Deep Dive into Probiotics for Histamine or Mast Cell issues

This is from a special analysis identifying bacteria that are probiotics that have association to histamines and mast cell issues using the 394 annotated samples contributed.

Some species are to be avoided. Keeping to the specified species is strongly recommended,

Tax_NameTax_rankSymptom
Frequency
No Symptom
Frequency
Suggests
Bifidobacterium adolescentisspecies33.548.8Take
Bifidobacterium pseudocatenulatumspecies8.97.7Avoid
Lactococcusgenus42.955.6Take
Bifidobacterium gallicumspecies18.827.7Take
Bifidobacterium kashiwanohense PV20-2strain10.720.3Take
Bifidobacterium indicumspecies27.439.8Take
Bifidobacteriumgenus83.894.4Take
Bifidobacterium catenulatum subsp. kashiwanohensesubspecies13.721.9Take
Bifidobacteriaceaefamily85.395.4Take
Bifidobacterialesorder85.595.4Take
Lactobacillus rogosaespecies22.826.6Take
Bifidobacterium bombispecies13.721.3Take
Lactobacillaceaefamily91.196.7Take
Lactobacillus inersspecies10.214.1Take
Bifidobacterium subtilespecies22.626.8Take
Lactobacillusgenus83.289Take
Bifidobacterium thermacidophilumspecies12.214.7Take
Lactobacillalesorder97100Take
Lactococcus lactisspecies1418.3Take

In terms of bacteria patterns found, the following were found statistically significant

Tax_NameTax_rankSymptom
Frequency
No Symptom
Frequency
unclassified Clostridialesfamily50.529.2Too many
Elusimicrobiaphylum8.43.8Too many
Prevotella paludivivensspecies9.619Too Few
Lacrimispora saccharolyticaspecies10.28Too many
Alistipes sp. NML05A004species13.77.7Too many
Proteusgenus8.47.4Too many
Butyricimonas sp. 214-4species10.74.7Too many
Bifidobacterium adolescentisspecies33.548.8Too Few
Pseudobutyrivibrio xylanivoransspecies35.349.7Too Few
Bacillales Family XI. Incertae Sedisnorank52.569.1Too Few
Papillibactergenus35.323.5Too many
Gemellagenus52.368.6Too Few
Tepidibactergenus10.916.7Too Few
Oribacterium sinusspecies55.671.2Too Few
Elusimicrobiaclass8.13.1Too many
Citrobacter freundii complexspecies group8.98.1Too many
Peptoclostridiumgenus23.618Too many
Natronincolagenus29.744Too Few
Prevotella coprispecies56.972.2Too Few
unclassified Alistipesnorank1911.9Too many
unclassified Butyricimonasnorank14.55.1Too many
Natronincola peptidivoransspecies26.141.3Too Few
Ruminococcus gnavusspecies6780.8Too Few
Veillonella disparspecies36.352.1Too Few
Streptococcus sanguinisspecies15.221.7Too Few
Caulobacteralesorder19.328.8Too Few
Caulobacteraceaefamily19.328.8Too Few
Streptococcus vestibularisspecies30.744Too Few
Caloramator mitchellensisspecies35.849.9Too Few
Streptococcus fryispecies17.828.9Too Few
Pectinatus cerevisiiphilusspecies28.942.7Too Few
Bifidobacterium pseudocatenulatumspecies8.97.7Too many
Anaerobranca zavarziniispecies27.939.8Too Few
Lactococcusgenus42.955.6Too Few
Natranaerobialesorder30.742.2Too Few

Bacteria interacting with Bacteria

Bacteria are like people, they interact and are influenced. The problem is how to detect the interactions that are clinically significant and the direction of interaction without grabbing stereotypes (i.e. all Italians belong to the Mafia, Irish are lazy, Egyptians are all Islamic Terrorists, etc).

We are going to look at two bacteria interacting: Phocaeicola massiliensis and Paraprevotella

To see the results for other bacteria, look up your favorite bacteria MicrobiomePrescription : Look up a bacteria taxa. See video at bottom for walk through.

The Classic Way

From a collection of samples, we pull all samples that report both bacteria. We take these numbers and drop them into a tool like Excel. Chart the data and try to do a linear regression. This is often pro-forma in research papers because that is rote learning.

A Uniform Way

This is almost the same, except we do not use the actual numbers, but the percentile rankings. This produce stronger regressions values Using the percentile transform the data to a uniform distribution. R2 increased by 10 fold but really a long away from significance.

You can almost see signs of a trend in the middle of lots of noise.

A Non-parametric Way

We use classic Chi2. The process is simple

  • For bacteria A we determine the percentage with a value of 100 or higher, say 5%
  • For bacteria B we determine the percentage with a value of 1000 or higher, say 5%
  • We filter the samples to those with bacteria A being higher than 100
  • If there are no interactions than we expect 5% of bacteria B to be 1000 or more.
  • If we find that 30% of bacteria B is more than 1000, then it appears that high Levels of A results in higher levels of B

From the above we can compute a statistics,Chi2, and thus the statistical significance. In this case, very very significant.

This means that we isolate the impact of high values and low values which the earlier methods did not do, We do not know how the middle value interact but for clinical issues, it is abnormally high and abnormally low values that are of interest.

Implementation

The first question is to pick the high and low threshold values. People can pick arbitrary values and try them. I have my own preference a patent pending algorithm to produce ranges.

The second question or issue is the number of computations. People can download my data set from https://citizenscience.microbiomeprescription.com/ and do the same calculation.

The number of calculations to be done were done in the following datasets with 5%ile and above, and 95%ile and above. The bigger the sample, the better sensitivity and more interactions likely to be discovered.

  • All: 5,191,562 possible pairs on 5189 samples –> 1,270,000+ Interactions found
  • Biomesight: 1,717,410 possible pairs on 2534 samples –> 275,000+ Interactions found
  • Ombre: 1,743,720 possible pairs on 1540 samples –> 220,000+ Interactions found
  • uBiome: 132,860 possible pairs on 791 samples –> 4,700+ Interactions found

For each pair of taxa we have 4 scenarios (Low versus Low, Low vs High, High vs High, High vs Low) Or about 32 million queries retrieving data sets and performing calculations. The bigger the sample size, the more items that are likely to be identified. For thresholds, we use a patent pending algorithm that appears to yield good results (shown above). The alternative would be to enumerate percentages and find the ones that work best (so 100 x 100 x 32 million = 320,000,000,000 queries).

Illustration of the code is below.

Select Sum(Case when c1.Percentile < 19.274700171330668 
                  /* 577309 Low Percentile Threshold*/
           then 1 else 0 End) Obs, /*Low Count that is filtered sample */
         Count(1) Cnt, /*Filtered sample Count*/
         cast(Count(1) * 19.274700171330668/100 as float) [Expected Value]
from UserCounts c1 Join Usercounts c2
on C1.sampleId=c2.sampleId
And C1.taxon=204516
And C2.Taxon=577309
Join Users U on C1.SampleId=SequenceId
Where c2.Percentile < 12.890741292051205 /* 577309 Low Percentile Threshold*/
Group by C1.Taxon,C2.Taxon
dependentindependentLabelObsDirectionExpectedChi2%
204516577309L,L158>7998.5200%
204516577309L,H204<238686%
204516577309H,L138<20239.568%
204516577309H,H724>60943.1119%
Phocaeicola massiliensisParaprevotella
Example of results with counts

There is a question of using Chi2 or using the percentage increased or decreased.

Example:

  • High Paraprevotella, we get more high count and less low count of Phocaeicola massiliensis. In other words Phocaeicola massiliensis numbers increase as a result (i.e. median likely moved up).
  • Low Example: Paraprevotella, we get less high count and more low count of Phocaeicola massiliensis. In other words Phocaeicola massiliensis numbers decrease as a result (i.e. median likely moved up).

Looking at doing linear regression, we do not see the relationship.

Chi2 Low Chi2 HighNumber of Interaction Found
6501427931
50150301973
15025035584
2503507966
3504503172
4505501303
550649695
9501050610
650750505
750850483
851950376
10511150349
12501350223
11501250218
13501450213
15511650158
14501549153
16511750141
18501949138
17511847126
1950205098
2050215083
2150224968
2252234864
2350244956
2451254833
2551265031
2951304328
2753284527
2659274127
3057315026
3153324223
3253334820
2856294919
3862394818
3365345016
4057414114
3470354812
3752384212
355536259
365237498
395640468
416242486
427843293
486749053
576357822
437344232
510251392
477147711
518951891
473747371
If you use your own limits, this can be used to determine if the limits are better or not.

Next Project

Many taxa shifts have nothing in the literature affecting the taxa for use in a clinical context. Identifying taxa with a strong interaction that we can affect should allow us to indirectly influence the target taxa. Yes, gets complex but with modern computer power, very possible to do.

Biomesight #4 Sample: IBS and COVID

We have a varied history with some storms blowing us off courses. Here’s a list of the tests and prior blog posts:

His comments are short:

  • I would say some small subjective improvements since last time, but no major changes. Reminder: I have a friendly MD in terms of antibiotics.
  • Metronidazole was on top in the last samples, I did it back then.
    • Comment: Metronidazole is no longer at the top but dropped down to 16% of the highest value. It appears to have done its magic in reducing the bacteria pointing to it as a tool..

Base Analysis

When people have multiple samples, I like to do side-by-side comparisons, especially when someone has been doing some of the suggestions suggested. The suggestions are computed and may not always work. Expert Systems and AI are not perfect; they typically do better than a person with only a few years of experience that has training in the discipline (better consistency, remember more facts, etc). How are we doing objectively?

Scores

We see two positive shifts in the latest sample: Increase of Anti inflammatory Bacteria Score and decrease of Histamine Producers.

Sample2021-11-182022-05-202023-06-222023-09-04
Anti inflammatory Bacteria Score54%ile43%ile63%ile87%ile 🥰
Butyrate Bacteria Score57%ile56%ile57%ile54%ile
Histamine Producers78%ile82%ile81%ile67%ile 🥰

Percentages of Percentiles

We see a lot of bouncing around between samples. The middle two images matches the typical pattern seen with ME/CFS and Long COVID. Those shifts have faded over the last 3 months with a different pattern appearing indicating a different dialect of gut dysfunction.

Multi-Vector Comparison

The main numbers are below. The take away, less bacteria that are in the high percentile range (at 95%ile, 10 -> 28 -> 23 -> 8). The numbers bounce around with the middle two being similar and the other two also similar. There are no really clear shift in these measures.

Criteria11/18/20215/20/20226/22/20239/4/2023
Lab Read Quality8.15.54.77.2
Outside Range from JasonH6699
Outside Range from Medivere16161515
Outside Range from Metagenomics8877
Outside Range from MyBioma5566
Outside Range from Nirvana/CosmosId20202323
Outside Range from XenoGene29293535
Outside Lab Range (+/- 1.96SD)76173
Outside Box-Plot-Whiskers36695438
Outside Kaltoft-Moldrup93484788
Bacteria Reported By Lab652508542558
Bacteria Over 99%ile7462
Bacteria Over 95%ile1028238
Bacteria Over 90%ile29423622
Bacteria Under 10%ile2084150175
Bacteria Under 5%ile180198157
Shannon Diversity Index1.8531.8261.2721.556
Simpson Diversity Index0.0560.0380.0870.09
Rarely Seen 1%2271
Rarely Seen 5%145218
Pathogens41242936

From Special Studies

The top match was the same on all of the samples, with an increase when there was actually COVID.

Criteria11/18/20215/20/20226/22/20239/4/2023
COVID19 (Long Hauler)28%ile33%ile41%ile28%ile
Next one:15%ile26%ile20%ile13%ile
The “next one” dropping implies some reduction of dysbiosis

Health Analysis

Using Dr. Jason Hawrelak Recommendations, there are many items on the edge of being in range with some items of interest (I strike out those that are unlikely to be of great concern):

  • Faecalibacterium prausnitzii at 27% of the microbiome or 96%ile
  • Akkermansia — 0.009 % of the microbiome or 35%ile
  • Bifidobacterium 0.016 % of the microbiome or 16%ile
  • Bacteroides – 27% of microbiome, or 64%ile

Additionally, two indicate increased risk of Candida (new feature just added)

  • Phocaeicola dorei at 10% of the microbiome or 91%ile
  • Faecalibacterium prausnitzii at 27% of the microbiome or 96%ile

I would suggest a test for candida to be safe. The data suggests a risk. If confirmed, candida would contribute significantly to gut dysbiosis [The interplay between gut bacteria and the yeast Candida albicans[2021]). I did a “back-flip” check of the top prescription items, and all of them reduces Candida (studies cited below).

Addendum – Predicted Symptoms

This was just added to the site today as a further refactor based on New Special Studies on Symptoms data. These are from [My Profile Tab]

Criteria11/18/20215/20/20226/22/20239/4/2023
Forecast Major SymptomsNeurological: Cognitive/Sensory Overload
40 % match on 25 taxa

DePaul University Fatigue Questionnaire : Racing heart
38 % match on 13 taxa

DePaul University Fatigue Questionnaire : Difficulty falling asleep
37 % match on 27 taxa

DePaul University Fatigue Questionnaire : Difficulty finding the right word
35 % match on 20 taxa
Autonomic Manifestations: urinary frequency dysfunction
66 % match on 6 taxa
Immune Manifestations: Bloating
37 % match on 45 taxa

Neurological-Audio: hypersensitivity to noise
35 % match on 28 taxa
NoneNeurological-Sleep: Chaotic diurnal sleep rhythms (Erratic Sleep)
50 % match on 18 taxa

Neurological: Spatial instability and disorientation
37 % match on 16 taxa

This can be helpful for judging possible severity (and potential improvement of some symptoms), for example: Neurological: Cognitive/Sensory Overload. See [Special Studies] tab.

  • 2021 – 40% matches
  • 2022- 24% matches
  • 6/22/23 – 16% matches
  • 9/4/2023 – 4% matches

Going Forward

COVID has had quite an impact on this microbiome. I am going to just go with the “Just Give Me Suggestions” option with the addition of what matched his diagnosis:

  • Irritable Bowel Syndrome  (68 %ile) 7 of 68

To explain a bit more. First I click the button below

And then click I could click the consensus report to see what the top items are:

Which are shown below.

In this case, I want to add Irritable Bowel Syndrome suggestions (on the Changing Microbiome Tab)

Instead of the usual 4 packages of suggestions, we have 5

When we look at the consensus report we see the same items there, but the values have increased.

The intent is put a little bias on the numbers towards specific conditions of greatest concern.

PDF Suggestions

I tend to favor the PDF suggestions because it simplifies things for many readers. Also the PDF gives a good list of citations (never complete) used to make the citations to persuade MDs to see that the suggestions are based on studies — a lot of studies.

The PDF suggestions are below (using the consensus view is another option for those more technically orientated). I clip from the PDF to keep the blog simpler for the typical reader.

This is a little longer list than usual, so I went to the consensus report to get priority data. Top value was 618, so 309 is the 50% threshold.

These appear to be of low influence with the exception of l.bulgaricus:

Minor note: quercetin with resveratrol is an avoid, quercetin is a take. resveratrol by itself is a negative (-113). At times, you need to look at the technical details/consensus to clarify things; the data we are using is incomplete and sparse…. If clearly contradictory suggestions appear, then don’t do them (thing an abundance of caution).

Because he has an antibiotic friendly MD, the following are the TOP antibiotics with notes:

CFS Antibiotics are also above the threshold. Since the prior sample had a strong Long COVID or ME/CFS Profile, I would be inclined to include one of those below in the antibiotic rotation. The microbiome cannot make a diagnosis of most things, with most ME/CFS microbiomes there is a particular pattern which you had in your last sample but which has disappeared from your current sample which looks more like your first sample. I read this as recovering from ME/CFS….  in likely a fragile state since relapse is very common with ME/CFS.

My own experience is that it is better to overcure ME/CFS and when there are signs of recovery…. no backflips of joy or running marathons; keep doing slow walks that becomes a bit further each week for 6-12 months. Your microbiome is fragile and can quickly slip back.

I prefer to use the strategy of going for prescription items that are both suggested from the microbiome and been shown to help with one or more of the diagnosis conditions. This usually encounter low resistance from physicians — they are clueless for the microbiome, but very accepting of published studies. An antibiotic that is used as a prophylaxis usually encounter little resistance.

KEGG Suggestions

This is done by using information from the bacteria found with some fudge factors. I am in discussion with some Ph.D. candidates to build this concept directly from the FASTQ files and will hopefully have this as an added feature next year.

The KEGG probiotics is the usual pattern for ME/CFS and Long COVID with the top one being the usual, with the top reasonably available ones for other families shown below. I usually like to compare the values with those from consensus to minimum risk (i.e. two thumbs up, we do; mixed, we skipped)

KEGG Supplements

From the list, we will look only at those with a z-score (statistical significance) over 2. After each we put the consensus value (if it is listed)

Only two items are with high confidence.

How to Proceed Suggestions

The suggestions should be thought as influencers. The human population is often a good analogy or parable for the microbiome population. Each influencer shifts the population in the desired direction. Based on Cecile Jadin’s work and several studies, I am a firm believer in short duration (1-2 weeks) of each influencers. Just as with human influencers, people stop listening if the same person just keeps droning on and on. If a different person starts speaking, you get persuaded more. If a mob start to shout, yet a different human behavior will occur. In terms of the microbiome, “stop listening” means mutations that are resistant to the item will start to increase. Items line vitamins and minerals can be taken continuously; items that are likely to have bacteria resistance developed should be taken for a week and then another item replace it.

The items to rotate:

  • Antibiotics listed above
  • Probiotics: lactobacillus salivarius and lactobacillus bulgaricus
  • Herbs and spices: cinnamon, ginger, black cumin, thyme, rosemary, quercetin (suggests just before each antibiotic with a few days of overlap because it has potential synergistic activity with antibiotics [2020], [2016],[2018] )

Remember our goal is to destabilize a stable microbiome dysfunction.

Questions and Answers

While there has not been significant changes in many of the vectors between this sample and the prior sample from a few months earlier, there has been two significant objective changes:

  • Significant improvement of Anti inflammatory Bacteria Score (higher) and Histamine Producers (Lower).
  • The lost of the ME/CFS – Long COVID spike in the 0-9%ile

Q: Do you/should I use the colored list now instead of the consensus list?

  • Either are fine, the color list (from PDF) is what I tend to use in post because it is easier for new readers to understand (and automatically sent on new uploads). The consensus page is more complex but allows people to apply their own logic and priorities.

Q: “Quercetin (suggests just before each antibiotic with a few days of overlap because it has potential synergistic activity with antibiotics”

Q: I just did Mutaflor for 8 days and felt really tired all the time (but in the end I also got a flu/cold, so maybe that was the reason and not mutaflor). Nevertheless, if it was a herx reaction, I wonder if I should have taken it for longer until the reaction disappeared? (I stopped it 4 days ago.) Not sure if this question even makes sense.

  • My personal choice would be to keep taking it for at least a week (perhaps 2). Remember that the traditional pattern for a herx is feeling bad for X hours and then things get better. The duration of the feeling bad usually decrease from day to day. Catching a cold makes interpretation challenging.

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 can compute items to take, those computations do not provide information on rotations etc.

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.

New Special Studies on Symptoms

Recently I did a much more rigorous implementation of the Kaltoft-Moldrup ranges as part of a periodic review and refactor. Today, I tested a hypothesis that those ranges may be good for detecting the taxa (bacteria) associated with a self-reporting symptom. The results exceeded expectations.

The methodology is simple to understand. Suppose we have 1000 samples. The KM lower limit is 5%ile and upper limit is 85%ile across the entire population.

For those with brain fog as a symptom we found that instead of the expected 5% of 1000 (i.e. 50), we only have just 5 samples in this range. That is a dramatic (and statistically significant shift).

On the other end, we do not have our expected 150 (100%-85% * 1000) but 300 sample in this range.

We can conclude that those with less than the 5%ile is associated with brain fog as well as those with more than 85%ile.

Most of the time we will find just one shift being significant. At times, both can be — i.e. values cascaded away from the range is both directions.

I have determined the taxa/bacteria for a stack of symptoms using P < 0.01. Because different labs identifies taxa information (see Nightmare ). This is why there is often no replication of (or contrary) results in many published studies. I created a table that is lab specific for each taxa.

Overview Page

This shows the number of bacteria found significant for each symptom. “All” usually will have more because it has more samples to use and thus can detect lesser associations better.

Link: https://microbiomeprescription.com/Library/CitizenScience

Detail Page

This page can get confusing because the labs use different sequences of RNA to infer the bacteria. The actual association

PDF A Priori Suggestions

This is done using the ALL profile.

New Scientist: You and Your Microbiome

The following are permissible extracts (200 words per article). Click [more] to read more…

How the microbiome changes our idea of what it means to be human

YOU may, quite reasonably, think you are an individual of the species Homo sapiens. Once you have finished reading what follows, you will hopefully have been convinced that there is far more to us than that. Trillions of other organisms live on (and, more notably, in) your body. As you will see in the reports that follow, their impact on you is such that you will probably never think about yourself in the same way again. Your microbes change who you are and what it means to be you. With knowledge of this facet of ourselves growing rapidly, exploring it has never been more relevant.

Until recently, scientists believed that there were three discrete parts of our nature that reflected solid aspects of an individual self: the immune system, the genome and the brain. “None of these pillars of the traditional definitions of the self – immunity, genome integrity, the central nervous system – are free of microbial impact,” says Thomas Bosch at Kiel University in Germany.

The microbes that colonise us, collectively known as the microbiome, challenge the concept of a discrete self. These include bacteria, viruses and fungi, although the bacteria are the best-studied. [more]

The best way to care for your microbiome to keep it healthy as you age

Your gut microbiome is a vital support system for mental and physical health, supplying the body with all-important nutrients and helping tune the immune system.  

As we get older, the balance of microbes in our gut changes. There are declines in beneficial types, such as the anti-inflammatory Faecalibacterium, and an increase in species that lead to more inflammation, which is implicated in multiple age-related conditions, including heart disease, cancer and cognitive decline. Many studies, with participants ranging from an isolated rural population in India to a wealthy semi-urban community in Italy, show striking similarities in the microbiome signatures of old age. One key finding is that people who have no significant health concerns in older age have an abundance of distinct beneficial microbes that are lost when there is a shift to physiological decline.

It isn’t clear whether the microbiomes of healthy older people are driving their vitality or are a result of the way they live, but an astonishing study in mice by John Cryan at University College Cork, Ireland, and his colleagues found that transplanting gut microbiota from young animals to elderly ones reversed age-associated impairments in brain function. [more]

Can probiotics and supplements really improve your gut microbiome?

If you have a condition like irritable bowel syndrome (IBS), a finnicky gut or just want to keep your microbiome in top condition, you might be tempted by products and treatments that offer a microbial tune-up. But what really works? Here are the main tools to engineer a better gut.

Probiotics

Probiotics are microbes that may help to restore healthy gut microbiota. If they also improve your mood, they are called psychobiotics. You can typically get them from eating naturally fermented foods like yogurt that contain beneficial bacteria, such as Lactobacillus or Bifidobacterium.

But as an adult, these microbes are unlikely to colonise your intestines. To the extent that they are helpful, their benefit comes while they are passing through. Such probiotics stimulate immune cells in the gut to reduce inflammation, increase mucus production and deter pathogens by producing lactic acid. But as mere visitors, they need daily top-ups.

Probiotic supplements have been used (with mixed success) for more than a century to help with the gut conditions of Crohn’s disease, colitis and IBS. They have also been shown to help with weight loss in people who are overweight and are increasingly being used for other conditions… [more]

Secrets of a long and healthy life reside in your gut microbiome

WHY do we age? As youngsters, we seem invincible. We climb trees, frolic in the dirt and blithely share alarming quantities of mucus. At college, we can thrive on a diet of ramen and beer, party all night and still sit an exam the next day. But in our 30s, we start to wind down. It becomes harder to maintain muscle tone and avoid illness. Our joints start to ache and our memory begins to dim. And it is mostly downhill from there.

People have long attempted to stop or reverse this process. But fountains of youth and secrets of immortality remain firmly in the realms of fiction. Our bodies wear out, even if we no longer do the back-breaking physical labour our ancestors did. And the world seems determined to grind us down with a plethora of disease-causing microbes. To help fend off these pathogens, our bodies recruit other microbes, vast numbers of which reside in our intestines, where we feed them in exchange for their services. But, as we age, this gut microbiota becomes less effective at fighting diseases too. [more]

Where does your gut microbiome really come from – and does it matter?

Imagine a remote island, recently formed by volcanic activity, in the middle of the ocean. At first, it is lifeless, but a growing variety of plants take hold, providing food for pioneering animal species, until eventually there is a diverse and flourishing ecosystem.

This is a useful way to think about how our gut ecosystems develop. “Your microbiome goes on a journey,” says Alan Walker at the University of Aberdeen, UK. “When you’re born, some bugs get in and then, when you start eating solid foods, other bugs replace them. There’s a dynamic process where your microbiome changes until you get to mid-to-late childhood. Then, through adult life, you’ve got a reasonably stable microbial community.”

Does a C-section affect a baby’s microbiome?

The first individuals that colonise an island can have long-lasting influences on its ecosystem, an idea known as the founder effect. Until recently, the thinking went that if the founder bacteria in a baby’s gut were unusual – because the baby was born by Caesarean section, for instance – this might disrupt their bacterial ecosystems. This idea has led some parents to take radical steps to get their children’s microbiomes back on the right track.  [more]

What is the role of the microbiome in diseases like chronic fatigue

ONE of the most compelling discoveries about the gut microbiome is its influence on the immune system. Between 70 and 80 per cent of immune cells are in the gut, where they are constantly communicating with microbes. This crosstalk helps fight disease, strengthen immune responses and regulate inflammation, our body’s first line of defence against infection. Controlling inflammation is critical, as too much damages cells and helps drive chronic illness.

It is no surprise, then, that a growing body of evidence implicates the gut microbiome in various chronic diseases, from arthritis to Alzheimer’s. It is still early days, and most of these findings only point to associations. But they raise the possibility that gut microbes may contribute to, or even cause, some of our most intractable conditions, an idea that has already inspired new treatments.

It is now well established that gut microbiomes in people with conditions like multiple sclerosis, type 1 and type 2 diabetes, Parkinson’s disease and even asthma differ significantly from those of people without an underlying illness. Two papers published earlier this year showed that people with chronic fatigue syndrome – also known as myalgic encephalomyelitis, or ME/CFS – have less of a gut bacterium called Faecalibacterium prausnitzii  [more]

How your microbiome is shaped by your friends, family, lovers and pets

When we are born, we get most of our gut microbes from our mothers (see “Where does your gut microbiome really come from – and does it matter?”). But as we get older and form other close relationships, including with intimate partners, friends and pets, we start to pick up their microbes too. This could potentially affect our risk of developing conditions like obesity, inflammatory bowel disease, asthma and allergies (see “What is the role of the microbiome in diseases like chronic fatigue?”).

“I jokingly say that your dating app profile should include your microbiome profile,” says Brett Finlay at the University of British Columbia in Canada.

The strongest evidence comes from work published in January by Mireia Valles-Colomer at the University of Trento, Italy, and her colleagues, who conducted the largest study to date of how our gut microbiomes are shaped by the people around us. They analysed DNA in the faeces of more than 7000 people from households around the world, including rural parts of Africa and South America and cities in the US, Europe and China, to find out which bacterial strains were in their guts and what proportion they shared with others. [more]

—————– from older issues ———————-

Your gut microbiome is linked to your fitness and biological age

The diversity of microbes in the gut could affect a person’s fitness and their biological age. Better understanding this may one day lead to probiotics that alter the gut’s microbial make-up to promote health.

Zsolt Radak at the Hungarian University of Sports Science and his colleagues studied 80 amateur rowers, aged 38 to 84, who participated in the 2019 World Rowing Masters Regatta in Velence, Hungary.

The rowers, whose training regimens ranged from practising every day to once a week, each provided a stool sample to identify the bacteria in their guts. The researchers also took blood samples to gauge the participants’ biological ages – a measure based on DNA markers, rather than the number of years someone has been alive.

The researchers found that having higher levels of gut microbiome diversity was linked to lower levels of fitness and an accelerated rate of biological ageing. This somewhat goes against previous research that linked lower gut microbial diversity to conditions such as obesity and type 2 diabetes. [more]