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. About 8 out of 10 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%.
I was unable to find any specific diseases / conditions associated with it.
Bottom Line
This is a fungi that I would take no action on because it does not appear to produce any clear harm. If you have other fungi of concern, the treatment of those will likely reduce this one. Some of it’s children are reported sensitive to Itraconazole.
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. About 8 out of 10 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%.
Thorne only provided only order-level information unfortunately.
CAUTION: Baby Bella and Button Mushrooms belong to this order. To prevent false positive for this order, refrain from any mushroom consumption for a week before the test.
Agaricales contains about 30 families, about 350 genera, and some 10,000 species. [Britannica]
“The patient was treated with voriconazole and itraconazole successively.”
Bottom Line
Our ability to drill down further is limited because the results only report at the family level. Itraconazole, an antifungal that is the top choice for other fungi reviewed appears to work. This order-level fungi has a significant risk of misidentification because it also contains common mushrooms that are consumed.
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. About 8 out of 10 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%.
Thorne only provided only order-level information unfortunately.
The Pleosporales is the largest order in the fungal class Dothideomycetes. By a 2008 estimate, it contained 23 families, 332 genera and more than 4700 species.[Wikipedia]
“Several of these Alternaria mycotoxins can have adverse effects on humans such as salivation, vomiting, erythema, convulsions, and gastrointestinal hemorrhage.”
Organisms of the genus Bipolaris [a member of Pleosporales] are found in the soil and plant material. These fungi are known to be plant pathogens and infection may result from either inoculation or inhalation of the organism. Infections due to this genus are probably more common than previously recognized and have been increasingly reported in apparently immunocompetent[healthy] hosts. Currently, they should be included in the differential diagnosis of disseminated fungal disease. Genus Bipolaris have been associated with central nervous system infections, sinusitis, keratitis, peritonitis associated with continuous ambulatory peritoneal dialysis, orbitopathy and allergic bronchopulmonary disease. . In addition to the ability of this genus to cause invasive as well as ‘allergic’ disease in humans, it is reported that a rnycotoxin produced by Bipolaris may induce lung and liver adenomas ill mice
Disseminated Bipolaris Infection in an Immunocompetent Host: An Atypical Presentation [2000]
Our ability to drill down further is limited because the results only report at the order level. Itraconazole, an antifungal that is the top choice for other fungi reviewed appears to work.
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%.
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.
“Different research found that Cordyceps militaris extract suppresses dextran sodium sulfate-induced acute colitis in BALB/c mice by suppressing disease symptoms such as body weight loss, diarrhea and gross bleeding. The extracts prevented shortening of the colon and crypt length and the epithelial damage” [2011]
“Moreover, recent studies have shown that Cordyceps pruinosa extract is a inhibitor of NF‐ κB activation and can enhance weak immune functions. Based on these facts, I hypothesize that Cordyceps pruinosa extract may thus exert its therapeutic effect on IBD by regulating NF‐κB activity and improving impaired immune functions” [2009]
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.
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 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%.
“The black yeast E. dermatitidiswas detected in 47% of the dishwashers, primarily at the dishwasher rubber seals, at up to 106 CFU/cm2“
“Eighteen percent of all of the washed items were contaminated with fungi, irrespective of the type of material they were made from.”
“Exophiala species are common environmental fungi often associated with decaying wood and soil enriched with organic wastes….Phaeohyphomycosis caused by Exophiala species has been reported in both normal and immunosuppressed patients.” [Mycology]
E. dermatitidis is, among other species, a common colonizer of the respiratory tract of patients with CF [2018]
“predisposing factors for E. dermatitidis infections are diabetes mellitus, steroid medication, concurrent bacterial and fungal infections and nutritional deficiencies” [2018]
“Immunosuppressed and elderly patients suffer from infections with E. dermatitidis most commonly in the form of phaeohyphomycosis, keratitis or chromoblastomycosis;”[2018]
“Fatal brain infections caused by the neurotropic E. dermatitidis occurred in otherwise healthy individuals in the Asian population” [2018]
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.”
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
Overview: The Malassezia Genus in Skin and Systemic Diseases [2012] which cites “A common characteristic of systemic infections of Malassezia yeasts in adults is the existence of a central venous catheter and total parenteral nutrition . Hematologic malignancies, cancer, and Crohn’s disease were the background of Malassezia systemic infections. ”
“the presence of Malassezia had significant consequences on the outcomes of Crohn’s disease models.” [2021]
“Pyrithione zinc kills Malassezia and all other fungi, and is highly effective against the Malassezia species actually found on scalp” [2005] – but that is a topical treatment.
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]
” 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 restricta. Malassezia was associated with the need for treatment escalation during follow-up”
“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 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%.
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.
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 Name
Tax rank
Tinnitus Mean
Others Mean
unclassified Herbaspirillum
norank
50.3
22.6
Lacrimispora saccharolytica
species
78.1
53.1
unclassified Sutterella
norank
31.1
52.6
Collinsella tanakaei
species
60.1
43.0
Prevotella paludivivens
species
32.9
48.7
Proteus
genus
61.6
46.0
Desulfonatronovibrio
genus
54.2
38.8
Tepidimicrobium xylanilyticum
species
62.3
47.1
Prevotella oralis
species
37.7
52.5
Bifidobacterium gallicum
species
33.1
47.9
Bifidobacterium adolescentis
species
36.7
48.8
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
Percentile
Expected
Obs
Chi2
1
0.79
13
190.6
9
7.11
29
74.1
10
7.9
30
68.7
22
17.38
40
37.7
31
24.49
45
24.9
36
28.44
49
23.2
47
37.13
51
9.8
49
38.71
52
8.9
50
39.5
53
9.2
51
40.29
54
9.5
52
41.08
55
9.8
53
41.87
56
10.1
54
42.66
58
12.0
55
43.45
60
14.0
56
44.24
61
14.4
62
48.98
62
9.1
63
49.77
63
9.5
64
50.56
65
11.5
68
53.72
66
8.8
69
54.51
66
7.8
71
56.09
67
7.3
72
56.88
68
7.8
73
57.67
69
8.2
75
59.25
71
9.3
78
61.62
72
7.9
79
62.41
74
10.2
86
67.94
75
5.2
91
71.89
76
2.6
93
73.47
77
2.4
96
75.84
78
1.5
99
78.21
79
0.8
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.
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.”
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.
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.
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_Name
Tax_rank
Symptom Frequency
No Symptom Frequency
Suggests
Bifidobacterium adolescentis
species
33.5
48.8
Take
Bifidobacterium pseudocatenulatum
species
8.9
7.7
Avoid
Lactococcus
genus
42.9
55.6
Take
Bifidobacterium gallicum
species
18.8
27.7
Take
Bifidobacterium kashiwanohense PV20-2
strain
10.7
20.3
Take
Bifidobacterium indicum
species
27.4
39.8
Take
Bifidobacterium
genus
83.8
94.4
Take
Bifidobacterium catenulatum subsp. kashiwanohense
subspecies
13.7
21.9
Take
Bifidobacteriaceae
family
85.3
95.4
Take
Bifidobacteriales
order
85.5
95.4
Take
Lactobacillus rogosae
species
22.8
26.6
Take
Bifidobacterium bombi
species
13.7
21.3
Take
Lactobacillaceae
family
91.1
96.7
Take
Lactobacillus iners
species
10.2
14.1
Take
Bifidobacterium subtile
species
22.6
26.8
Take
Lactobacillus
genus
83.2
89
Take
Bifidobacterium thermacidophilum
species
12.2
14.7
Take
Lactobacillales
order
97
100
Take
Lactococcus lactis
species
14
18.3
Take
In terms of bacteria patterns found, the following were found statistically significant
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).
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 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
dependent
independent
Label
Obs
Direction
Expected
Chi2
%
204516
577309
L,L
158
>
79
98.5
200%
204516
577309
L,H
204
<
238
6
86%
204516
577309
H,L
138
<
202
39.5
68%
204516
577309
H,H
724
>
609
43.1
119%
Phocaeicola massiliensis
Paraprevotella
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 High
Number of Interaction Found
6
50
1427931
50
150
301973
150
250
35584
250
350
7966
350
450
3172
450
550
1303
550
649
695
950
1050
610
650
750
505
750
850
483
851
950
376
1051
1150
349
1250
1350
223
1150
1250
218
1350
1450
213
1551
1650
158
1450
1549
153
1651
1750
141
1850
1949
138
1751
1847
126
1950
2050
98
2050
2150
83
2150
2249
68
2252
2348
64
2350
2449
56
2451
2548
33
2551
2650
31
2951
3043
28
2753
2845
27
2659
2741
27
3057
3150
26
3153
3242
23
3253
3348
20
2856
2949
19
3862
3948
18
3365
3450
16
4057
4141
14
3470
3548
12
3752
3842
12
3555
3625
9
3652
3749
8
3956
4046
8
4162
4248
6
4278
4329
3
4867
4905
3
5763
5782
2
4373
4423
2
5102
5139
2
4771
4771
1
5189
5189
1
4737
4737
1
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.
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