This is a common symptom for many people. This is reported often in samples, and thus being examined if it reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. It does. We are not being specific about the type of fatigue. Each person use their own subject definition of fatigue, thus we do not expect strong statistical associations (and do not get it!)

Study Populations:

I include values for Special Studies: General ME/CFS below

Symptom	Reference	Study
General Fatigue	1095	134

• Bacteria Detected with z-score > 2.6: found 158 items, highest value was 5.3 (ME/CFS was 6.6)
• Enzymes Detected with z-score > 2.6: found 410 items, highest value was 6.0 (ME/CFS was 4.5)
• Compound Detected with z-score > 2.6: found 67 items, highest values was -4/4 (ME/CFS was 3.1)

So we have a weaker bacteria signature but stronger enzymes and compound signature than ME/CFS. Many people marking one will mark the other… so get your sodium chloride crystals out!

Interesting Significant Bacteria

All bacteria found significant had too low levels. The list of those with a z-score over 5 is small. Low Prevotella copri and Escherichia coli which appears on special studies on many co-morbid symptoms. The good news, is that there is work ongoing to produce a prevotella copri probiotic and several Escherichia coli probiotics are available.

We do see a few overgrowth These are seen only in some subsets.

Bacteria	Reference Mean	Study	Z-Score
Lactiplantibacillus pentosus (species)	114	22	5.3
Prevotella copri (species)	68098	21864	5.2
Gammaproteobacteria (class)	14382	5944	5.2
Veillonella (genus)	4022	2324	5.1
Escherichia coli (species)	829	196	5

Interesting Enzymes

Most enzymes found significant had too low levels. A few were higher (12 of 410), which are listed in a second table below

Enzyme	Reference Mean	Study Mean	Z-Score
[cysteine desulfurase]-S-sulfanyl-L-cysteine:[molybdopterin-synthase sulfur-carrier protein]-Gly-Gly sulfurtransferase (2.8.1.11)	5407	2420	6
3-(cis-5,6-dihydroxycyclohexa-1,3-dien-1-yl)propanoate:NAD+ oxidoreductase (1.3.1.87)	597	144	5.5
3-phenylpropanoate,NADH:oxygen oxidoreductase (2,3-hydroxylating) (1.14.12.19)	611	148	5.5
deoxyribocyclobutadipyrimidine pyrimidine-lyase (4.1.99.3)	4311	1668	5.5
tRNA-uridine65 uracil mutase (5.4.99.26)	4201	1733	5.4
S-adenosyl-L-methionine:23S rRNA (guanine2069-N7)-methyltransferase (2.1.1.264)	5850	3067	5.3
propanoyl-CoA:oxaloacetate C-propanoyltransferase (thioester-hydrolysing, 1-carboxyethyl-forming) (2.3.3.5)	1575	501	5.2
N4-acetylcytidine amidohydrolase (3.5.1.135)	3083	1279	5.2
ATP:D-tagatose 6-phosphotransferase (2.7.1.101)	415	112	5.1
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate pyruvate-lyase (succinate-forming) (4.1.3.30)	1524	484	5.1
acyl-CoA:sn-glycerol-3-phosphate 1-O-acyltransferase (2.3.1.15)	3385	1438	5.1
S-adenosyl-L-methionine:tRNA (cytidine32/uridine32-2′-O)-methyltransferase (2.1.1.200)	3437	1390	5.1
2-(glutathione-S-yl)-hydroquinone:glutathione oxidoreductase (1.8.5.7)	3263	1099	5.1
galactitol-1-phosphate:NAD+ oxidoreductase (1.1.1.251)	1042	292	5
acetyl-CoA:[elongator tRNAMet]-cytidine34 N4-acetyltransferase (ATP-hydrolysing) (2.3.1.193)	3430	1387	5
S-adenosyl-L-methionine:23S rRNA (uracil747-C5)-methyltransferase (2.1.1.189)	3379	1385	5
ATP phosphohydrolase (ABC-type, thiamine-importing) (7.6.2.15)	3637	1454	5
[50S ribosomal protein L16]-L-Arg81,2-oxoglutarate:oxygen oxidoreductase (3R-hydroxylating) (1.14.11.47)	3448	1440	5
7,8-dihydroneopterin 3′-triphosphate diphosphohydrolase (3.6.1.67)	3719	1634	5
ATP:N-acetyl-D-glucosamine 6-phosphotransferase (2.7.1.59)	3383	1369	5

Enzyme	Reference Mean	Study Mean	Z-Score
CTP:N,N’-diacetyllegionaminate cytidylyltransferase (2.7.7.82)	59568	76504	-2.9
1-phosphatidyl-1D-myo-inositol:a very-long-chain (2’R)-2′-hydroxy-phytoceramide phosphoinositoltransferase (2.7.1.227)	39144	50749	-2.9
1,5-anhydro-D-mannitol:NADP+ oxidoreductase (1.1.1.292)	65010	81029	-2.9
alginate oligosaccharide 4-deoxy-alpha-L-erythro-hex-4-enopyranuronate-(1->4)-hexananopyranuronate lyase (4.2.2.26)	79725	99196	-2.8
phosphatidylglycerophosphate phosphohydrolase (3.1.3.27)	87820	105463	-2.7
chondroitin-sulfate-ABC endolyase (4.2.2.20)	71773	88107	-2.7
chondroitin-sulfate-ABC exolyase (4.2.2.21)	71773	88107	-2.7
arabinogalactan 4-beta-D-galactanohydrolase (3.2.1.89)	107701	128121	-2.7
cephalosporin-C acetylhydrolase (3.1.1.41)	86153	104494	-2.7
UDP-N-acetyl-alpha-D-glucosamine 4-epimerase (5.1.3.7)	83349	100761	-2.6
N-sulfo-D-glucosamine sulfohydrolase (3.10.1.1)	59634	73685	-2.6
6-alpha-D-glucan 6-glucanohydrolase (3.2.1.11)	64035	78529	-2.6
GDP-alpha-D-mannose:2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol 6-alpha-D-mannosyltransferase (configuration-retaining) (2.4.1.346)	43744	55284	-2.6

Interesting Compound

Unlike most of the special studies we have many compounds that are significant. I have listed the high and low in separate tables below. Spot checking most of these found no useful information. For Maltodextrin which becomes  glucose would fit with fatigue — i.e. low sugar being produced.

Of the low items, the following appear to be available as supplements and potentially could help with fatigue

• Maltodextrin
• Inosine
• Thymine (Vitamin B1)
• Cytosine (as N-acetylcysteine)

Names	Z-Score
beta-D-Ribofuranose (C16639)	4
1,2-Diacyl-3-alpha-D-glucosyl-sn-glycerol (C06364)	3.8
Coproporphyrin III (C05770)	3.3
Cys-Gly (C01419)	3.2
Deoxyinosine (C05512)	3.2
UDP-N-acetyl-alpha-D-glucosamine 3′-phosphate (C20245)	3.2
Inosine (C00294)	3.1
Carboxylate (C00060)	3.1
Thymine (C00178)	2.9
3-(4-Hydroxyphenyl)pyruvate (C01179)	2.9
Acetoacetyl-CoA (C00332)	2.8
beta-D-Galactosyl-(1->3)-N-acetyl-D-galactosamine (C07278)	2.8
Prokaryotic ubiquitin-like protein (C21177)	2.8
dTDP (C00363)	2.7
tRNA with a 3′ CCA end (C19085)	2.7
Cytosine (C00380)	2.7
alpha-D-Aldose 1-phosphate (C00991)	2.7
5′-O-Phosphonoadenylyl-(3′->5′)-adenosine (C22092)	2.7
Hexadecanoic acid (C00249)	2.6
Maltodextrin (C01935)	2.6
Hydroquinone (C15603)	2.6

Names	Z-Score
beta-D-Ribopyranose (C08353)	-4
Chitobiose (C01674)	-3.6
Deoxyadenosine (C00559)	-3.5
Glutaredoxin (C07292)	-3
tRNA(Leu) (C01645)	-3
Lacto-N-biose (C06372)	-3
alpha-D-Glucosamine 1-phosphate (C06156)	-3
Pantetheine 4′-phosphate (C01134)	-2.9
UDP-N-acetylmuramate (C01050)	-2.9
L-Formylkynurenine (C02700)	-2.9
tRNA uridine (C00868)	-2.9
(S)-3-Hydroxybutanoyl-CoA (C01144)	-2.9
Amino acid (C00045)	-2.8
1,2-Diacyl-sn-glycerol (C00641)	-2.8
L-Glutamate 5-semialdehyde (C01165)	-2.8
Taurine (C00245)	-2.8
tRNA with a 3′ cytidine (C19078)	-2.8
tRNA precursor (C02211)	-2.8
Sucrose (C00089)	-2.8
UTP (C00075)	-2.8
beta-D-Glucose 1-phosphate (C00663)	-2.8
UDP-N-acetylmuramoyl-L-alanyl-gamma-D-glutamyl-L-lysine (C05892)	-2.7
tRNA(Lys) (C01646)	-2.7
L-Threonine (C00188)	-2.7
2-Succinylbenzoate (C02730)	-2.7
Oxygen (C00007)	-2.7
UDP-sugar (C05227)	-2.7
Phenyl acetate (C15583)	-2.7
Isopentenyl diphosphate (C00129)	-2.7
Cyclomaltodextrin (C00973)	-2.7

Similarly, items that are too high are likely to be avoided, including the following

• Sucrose
• Taurine
• Threonine

All of these suggestions are theoretical based in the model. Some literature to consider that appears to confirm the above (a.k.a. cross-validation)

• A caffeine-maltodextrin mouth rinse counters mental fatigue [2018]
• Effect of inosine supplementation on aerobic and anaerobic cycling performance [1996]
• Thiamine and fatigue in inflammatory bowel diseases: an open-label pilot study [2013]

Bottom Line

II was not expecting much from this special study. I was pleased to see some suggestions being generated that can be implemented (or soon will be)

• Probiotics:
  • Escherichia coli
  • Prevotella copri
• Supplements
  • Maltodextrin
  • Inosine
  • Thymine (Vitamin B1)
  • Cytosine (as N-acetylcysteine)

In looking at the suggestions below, remember we are using two very different models. Above we use KEGG data to identify what the bacteria are producing (the items going to the farmer’s market). Below, we use what has been reported to influence the population of the bacteria that we are too low in (i.e. “Fertilizer”)

This is a common symptom for many people. This is reported often in samples, and thus being examined if it reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. It does.

• “Motility” is a term used to describe the contraction of the muscles that mix and propel contents in the gastrointestinal (GI) tract. [Src] thus it has similarity to constipation (See Special Studies: Constipation)

• “An excess of intracolonic saturated long-chain fatty acids (SLCFAs) was associated with enhanced bowel motility in NMS rats. Heptadecanoic acid (C17:0) and stearic acid (C18:0), as the most abundant odd- and even-numbered carbon SLCFAs in the colon lumen, can promote rat colonic muscle contraction and increase stool frequency” [2018]

Study Populations:

Symptom	Reference	Study
Poor gut motility	1171	55

• Bacteria Detected with z-score > 2.6: found 170 items, highest z-score value was 8.8
• Enzymes Detected with z-score > 2.6: found 336 items, highest z-score value was 6.4
• Compound Detected with z-score > 2.6: found No items

Interesting Significant Bacteria

All bacteria that was found significant are too low. This is a common pattern for most of the special studies and really challenge the internet myth of the cause being too many bad bacteria. One bacteria really stands out — and there is ongoing work on making this one bacteria, Prevotella copri , available as a probiotics!

Bacteria	Reference Mean	Study	Z-Score
Prevotella copri (species)	64568	5498	8.8
Sutterella stercoricanis (species)	3098	410	7.5
Prevotella paludivivens (species)	144	26	7.1
Prevotella (genus)	72220	20587	6.2
Alkalibacterium (genus)	102	21	6
Prevotellaceae (family)	79801	32549	5.2
Leptospiraceae (family)	67	24	5.2
Leptospira (genus)	67	24	5.2
Leptospirales (order)	67	24	5.2
Leptospira licerasiae (species)	67	24	5.2
Ruminiclostridium (genus)	1000	348	5.1
Phocaeicola sartorii (species)	807	375	5.1

• “For example, abundances of Lactobacillus, Prevotella and Alistipes spp. are significantly decreased in patients with constipation ” [2018]

Interesting Enzymes

Most of the enzymes are too low, however a few are too high which is not the usual pattern seen in other of these special studies.

S-methyl-5′-thioadenosine:phosphate S-methyl-5-thio-alpha-D-ribosyl-transferase (2.4.2.28)	3740	1373	6.4
n/a (3.4.14.13)	1270	248	5.9
D-alanine:2-oxoglutarate aminotransferase (2.6.1.21)	2687	959	5.9
1-aminocyclopropane-1-carboxylate aminohydrolase (isomerizing) (3.5.99.7)	1428	337	5.9
succinyl-CoA:3-oxo-acid CoA-transferase (2.8.3.5)	1307	291	5.8
N-acyl-D-amino acid amidohydrolase (3.5.1.81)	1777	396	5.8
4-hydroxyphenylpyruvate:oxygen oxidoreductase (hydroxylating, decarboxylating) (1.13.11.27)	1446	225	5.6
carotenoid beta-end group lyase (ring-opening) (5.5.1.19)	1450	134	5.6
ATP:L-threonine O3-phosphotransferase (2.7.1.177)	2320	486	5.6
n/a (3.4.15.6)	1585	391	5.6
hydrogen-sulfide:flavocytochrome c oxidoreductase (1.8.2.3)	1164	108	5.5
15-cis-phytoene:acceptor oxidoreductase (lycopene-forming) (1.3.99.31)	2233	902	5.5
all-trans-zeta-carotene:acceptor oxidoreductase (1.3.99.26)	2233	902	5.5
15-cis-phytoene:acceptor oxidoreductase (zeta-carotene-forming) (1.3.99.29)	2233	902	5.5
15-cis-phytoene:acceptor oxidoreductase (neurosporene-forming) (1.3.99.28)	2233	902	5.5
[SoxY protein]-S-sulfosulfanyl-L-cysteine sulfohydrolase (3.1.6.20)	1183	106	5.5
CTP:5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-alpha-L-manno-nonulosonic acid cytidylyltransferase (2.7.7.81)	1139	119	5.5
medium-chain acyl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase (1.3.8.7)	1300	325	5.4
2-carboxy-2,5-dihydro-5-oxofuran-2-acetate lyase (ring-opening) (5.5.1.2)	1332	198	5.3
sulfite:oxygen oxidoreductase (1.8.3.1)	1199	107	5.3
alkane,reduced-rubredoxin:oxygen 1-oxidoreductase (1.14.15.3)	1087	107	5.3
4-hydroxybenzoate,NADPH:oxygen oxidoreductase (3-hydroxylating) (1.14.13.2)	1319	203	5.2
protocatechuate:oxygen 3,4-oxidoreductase (ring-opening) (1.13.11.3)	1319	199	5.2
dihydro-NAD(P):oxygen oxidoreductase (H2O2-forming) (1.6.3.5)	1290	145	5.2
glutaryl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase (decarboxylating) (1.3.8.6)	1257	258	5.2
3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming) (6.4.1.4)	1114	205	5.1
N-acyl-L-homoserine-lactone amidohydrolase (3.5.1.97)	1044	126	5.1
4a-hydroxytetrahydrobiopterin hydro-lyase (6,7-dihydrobiopterin-forming) (4.2.1.96)	1314	223	5.1

Too High Enzymes

Enzyme	Reference Mean	Study Mean	Z-Score
L-leucyl-tRNALeu:[protein] N-terminal L-lysine/L-arginine leucyltransferase (2.3.2.6)	130285	170931	-2.9
polyphosphate phosphohydrolase (3.6.1.11)	171217	211918	-2.8
guanosine-5′-triphosphate-3′-diphosphate 5′-phosphohydrolase (3.6.1.40)	171217	211918	-2.8
1-deoxy-D-xylulose 5-phosphate:thiol sulfurtransferase (2.8.1.10)	198195	242062	-2.7
(R)-2-carboxy-2,5-dihydro-5-oxofuran-2-acetate carboxy-lyase (4,5-dihydro-5-oxofuran-2-acetate-forming) (4.1.1.44)	199133	242528	-2.7
ATP phosphohydrolase (P-type, Ca2+-transporting) (7.2.2.10)	234154	280063	-2.7
acetyl-CoA:maltose O-acetyltransferase (2.3.1.79)	206724	252634	-2.7
3-methylbut-3-en-1-yl-diphosphate:ferredoxin oxidoreductase (1.17.7.4)	239452	285669	-2.7
L-aspartate:tRNAAsp ligase (AMP-forming) (6.1.1.12)	244534	289637	-2.6
5,10-methylenetetrahydrofolate:dUMP C-methyltransferase (2.1.1.45)	245078	290417	-2.6
D-arabinose aldose-ketose-isomerase (5.3.1.3)	188214	231505	-2.6
L-fucose aldose-ketose-isomerase (5.3.1.25)	188214	231505	-2.6
5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase (1.5.1.3)	247230	291626	-2.6

Bottom Line

While poor gut motility is often assumed to be due too many of some bacteria, the evidence suggestions that not enough is the more likely cause. There appears to be no simple model or answer.

• “The gut bacterium Prevotella copri (P. copri) has been shown to lower blood glucose levels in mice as well as in healthy humans, and is a promising candidate for a next generation probiotic aiming at prevention or treatment of obesity and type 2 diabetes” [2021]
• Cultivation of the gut bacterium Prevotella copri DSM 18205^T using glucose and xylose as carbon sources
• Prevotella copri as Next Generation Probiotics [firm that provides different strains for research purposes]

Prevotella copri will hopefully be available as a probiotic in a few year. There are two natural sources for P.Copri : Beer and Sauerkraut [2020], which may be an experiment for those that are prone to poor gut motility..

• “This species is more prevalent in non-Western populations likely due to its association with high fibre low fat diets” [2022]
• “Across all ethnicities, only coffee consumption was associated with an increased Prevotella relative abundance ” [2022]
• “Ancient stool samples suggest Westernization leads to P. copri underrepresentation” [2019]

The real bottom line is changing diet significantly. Consider some Indian style of food as part of supper every day, some examples ready to heat are here.

It should be noted that the B-Vitamins below are likely in the avoid list because they are usually provided thru meat in traditional diet.

This is a devastating mental infection of many people suffering severe ongoing health issues. The mythology is simple “Fix the root cause, and you will get better!” For acute, send yourself to the hospital, diseases this may be true, but there is another class of conditions where it is false.

Example, you developed rickets and developed skeletal deformities such as:

• Bowed legs or knock knees
• Thickened wrists and ankles
• Breastbone projection.

We know the root cause, not sufficient vitamin D. Will taking vitamin-D correct the skeletal deformities? No. Treatment will slow progression. You have lung cancer because you are a heavy smoker, will stop smoking cure lung cancer? You have Long COVID, ah the cure is to always wear a N95 mask?

Yes There was a Cause likely, but…

For items dealing with the microbiome, the cause starts a microbiome cascade that keeps going onwards. Think of a land slide, things are changed. There are side-effects like impact on fish or even getting into towns. So people start trying to cure the landslide by clearing the river or building a new road or…. and those attempt at curing, could cause more problems.

The best example that is well documented is the Bergen’s Giardia Infection. The root cause was Giardia infection. They eliminated the giardia — but the IBS, ME/CFS issues remained. They very well documented the root cause and dealt with it. No magical recovery.

Going Forward

I view many conditions as being supported (in a few cases totally caused) by the microbiome. Finding the root cause is very very unlikely to impact treatment and the way back to health. Focus on what is contributing to your current state and not ancient history!

I just banned someone called Ross Walter

Why? he has twice attacked me ad hominem (i.e. an attack on the person). I have made no secret that I am a high functioning ASD person (functioning in terms of mathematics), and that I did not learn to speak or form sentences until I was 9 y.o. I know that items like grammar are a great weakness. To attack a person with a recognized disability, for a disability is neither polite nor acceptable.
I apologize if my grammar is not perfect — my blog is not intended to be a literary masterpiece, but to convey data!

Alternative Title: Climate Change and your guts!

This is a common symptom for both ME/CFS and Long COVID. This is reported often in samples uploaded. We examine if the data reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. It does.

My default view is that this symptom is likely due to vesicular constriction/inflammation or “sticky blood” (which contains many possible coagulation issues). This results in slow blood flow causing issues with transferring heat to and from the body.

• temperature intolerance is generally placed under dysautonomia

Study Populations:

Symptom	Reference	Study
Intolerance of extremes of heat and cold	1159	54

• Bacteria Detected with z-score > 2.6: found 247 items, highest value was 8.8
• Enzymes Detected with z-score > 2.6: found 501 items, highest value was 6.7
• Compound Detected with z-score > 2.6: found No items

The number of bacteria and enzymes that are significant hints that it is a complex scenario, possibly with different subsets.

Interesting Significant Bacteria

All bacteria found significant had too low levels. The dominant order is Anaeroplasmatales and three significant genus are Holdemanella, Eubacterium, and Escherichia. Every one of the 247 bacteria found significant was LOW.

Bacteria	Reference Mean	Study	Z-Score
Holdemanella biformis (species)	3370	350	8.8
Holdemanella (genus)	3379	350	8.8
Eubacterium (genus)	2507	586	7.8
Lysobacter deserti (species)	29	11	6.5
Anaerolineae (class)	87	35	5.7
Opitutae (class)	163	46	5.5
Puniceicoccaceae (family)	158	44	5.5
Legionellales (order)	82	41	5.4
Leptospiraceae (family)	67	22	5.4
Leptospira (genus)	67	22	5.4
Leptospirales (order)	67	22	5.4
Leptospira licerasiae (species)	67	22	5.4
Bifidobacterium cuniculi (species)	79	26	5.3
Lactiplantibacillus pentosus (species)	116	22	5.3
Puniceicoccales (order)	110	37	5.3
Legionellaceae (family)	81	41	5.2
Legionella (genus)	81	41	5.2
Anaeroplasmataceae (family)	8102	20	5.2
Anaeroplasma (genus)	8102	20	5.2
Anaeroplasmatales (order)	8102	20	5.2
Chloroflexi (phylum)	128	55	5.1
Cerasicoccus arenae (species)	537	80	5.1
Caldilineaceae (family)	90	35	5.1
Caldilinea (genus)	90	35	5.1
Caldilineales (order)	90	35	5.1
Caldilinea tarbellica (species)	90	35	5.1
Caldilineae (class)	90	35	5.1
Escherichia (genus)	6016	1367	5.1
Cerasicoccus (genus)	312	60	5

Interesting Enzymes

Atypical distribution for enzymes in these studies, the number of highs and lows were of the same magnitude. 268 enzymes were low and 233 enzymes were high (see 2nd table) but none above our listing threshold of 5.0.

Enzyme	Reference Mean	Study Mean	Z-Score
(S)-2-hydroxyglutarate:quinone oxidoreductase (1.1.5.13)	2214	398	6.7
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate pyruvate-lyase (succinate-forming) (4.1.3.30)	1444	360	6.3
propanoyl-CoA:oxaloacetate C-propanoyltransferase (thioester-hydrolysing, 1-carboxyethyl-forming) (2.3.3.5)	1491	387	6.3
propanoate:CoA ligase (AMP-forming) (6.2.1.17)	1894	483	6.1
D-galactaro-1,4-lactone lyase (ring-opening) (5.5.1.27)	1698	393	5.8
thiosulfate:ferricytochrome-c oxidoreductase (1.8.2.2)	1381	272	5.4
gamma-butyrobetainyl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase (1.3.8.13)	1400	441	5.4
glutarate, 2-oxoglutarate:oxygen oxidoreductase ((S)-2-hydroxyglutarate-forming) (1.14.11.64)	1299	297	5.4
(E)-4-(trimethylammonio)but-2-enoyl-CoA:L-carnitine CoA-transferase (2.8.3.21)	1386	440	5.4
L-carnitinyl-CoA hydro-lyase [(E)-4-(trimethylammonio)but-2-enoyl-CoA-forming] (4.2.1.149)	1444	321	5.4
2-dehydrotetronate isomerase (5.3.1.35)	1406	482	5.3
(2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate hydro-lyase [(Z)-but-2-ene-1,2,3-tricarboxylate-forming] (4.2.1.79)	1297	439	5.2
3-phenylpropanoate,NADH:oxygen oxidoreductase (2,3-hydroxylating) (1.14.12.19)	581	142	5.2
1-aminocyclopropane-1-carboxylate aminohydrolase (isomerizing) (3.5.99.7)	1431	416	5.2
n/a (3.4.23.49)	1307	326	5.2
3-(cis-5,6-dihydroxycyclohexa-1,3-dien-1-yl)propanoate:NAD+ oxidoreductase (1.3.1.87)	568	140	5.2
ATP:2′-deoxyadenosine 5′-phosphotransferase (2.7.1.76)	1974	344	5.2
carotenoid beta-end group lyase (ring-opening) (5.5.1.19)	1452	201	5.1
RNA-3′-phosphate:RNA ligase (cyclizing, AMP-forming) (6.5.1.4)	1220	316	5.1
NTP:deoxycytidine 5′-phosphotransferase (2.7.1.74)	1885	287	5.1
L-threonate:NAD+ 2-oxidoreductase (1.1.1.411)	1410	492	5.1
succinyl-CoA:3-oxo-acid CoA-transferase (2.8.3.5)	1307	363	5.1
acyl-CoA,ferrocytochrome b5:oxygen oxidoreductase (6,7 cis-dehydrogenating) (1.14.19.3)	1063	277	5
L-carnitine:CoA ligase (AMP-forming) (6.2.1.48)	1373	517	5
hydrogen-sulfide:flavocytochrome c oxidoreductase (1.8.2.3)	1165	161	5
L-methionine methanethiol-lyase (deaminating; 2-oxobutanoate-forming) (4.4.1.11)	1272	288	5
L-carnitine,NAD(P)H:oxygen oxidoreductase (trimethylamine-forming) (1.14.13.239)	1186	320	5
4-hydroxy-2-oxoglutarate glyoxylate-lyase (pyruvate-forming) (4.1.3.16)	29	9	5

Bottom Line

Temperature intolerance is not an independently study topic. Existing studies are usually in the context of some other condition. This suggests that this is the first study on it’s microbiome.

•  “Diabetes is often associated with orthostatic hypotension and temperature intolerance.” [2005]

The suggestions below has some surprises on the to avoid list: Vitamins B-3, B-12, Curcumin,  N-Acetyl Cysteine (NAC) sitting high in the list with antibiotics. The absence of probiotics in the to take suggestions is note worthy for those that view probiotics as ‘cure all’. Not listed, but conceptually worth considering, are the E.Coli probiotics (Symbioflor-2 or Mutaflor).

Recently I have see pea appear often and I recall that peas were served with most meals as a child. Peas has largely disappear from the western menu. I am starting to wonder if having pea soup 3 times a week would help a lot of people.

This is a common symptom for many people. This is reported often in samples, and thus being examined if it reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. It does. We are not being specific about the type of constipation.

Study Populations:

We have 2 symptom annotations that could be included

• Comorbid: Constipation and diarrhea (not explosions) – 29 only
• Comorbid: Constipation and Explosions (not diarrhea) – 11 only
• Immune Manifestations: Constipation – 9.7 max z-score (70)
  • All of the above Constipation – 9.9 max z-score (83)

Taking all together we get 83 samples with an max z-score of 9.9

Symptom	Reference	Study
Constipation	1123	83

• Bacteria Detected with z-score > 2.6: found 123 items, highest value was 9.9
• Enzymes Detected with z-score > 2.6: found 511 items, highest value was 5.2
• Compound Detected with z-score > 2.6: found No items

Clearly some bacteria have strong associations, but the number of enzymes that are significant suggests that they may be more dimensions to the issue.

Previous studies have shown that the gut microbiota of constipated patients differs from healthy controls; however, many discrepancies exist in the findings, and no clear link has been confirmed between chronic constipation and changes in the gut microbiota.

Gut Microbiota Composition Changes in Constipated Women of Reproductive Age [2021]

The reason that I do not have Constipation on my US National Library of Medicine Studies list is that the studies are usually in the context of another microbiome altering condition. For example: Effects of Fermented Milk Containing Lacticaseibacillus paracasei Strain Shirota on Constipation in Patients with Depression [2021]

Interesting Significant Bacteria

Unusually bacteria was found significant with both high (13) and low (110). This far exceed the count expected as the false detection rate, so we should include and cite them.

Bacteria	Reference Mean	Study	Z-Score
Prevotella copri (species)	67087	7150	9.9
Prevotella (genus)	74786	17755	8
Prevotellaceae (family)	82267	29219	6.8
Veillonella (genus)	4003	2102	5
Lactiplantibacillus pentosus (species)	117	26	5

UNLIKE most of the other studies, we had a significant number of too many bacteria (far more than expected with a False Detection Rate).

Bacteria	Reference Mean	Study	Z-Score
Tannerellaceae (family)	24592	34890	-3.6
Parabacteroides (genus)	24587	34665	-3.6
Porphyromonadaceae (family)	26584	36605	-3.4
Bacteroides uniformis (species)	25682	42170	-3.2
Bacteroidaceae (family)	281711	337344	-3.1
Desulfosporosinus auripigmenti (species)	18	28	-3
Hathewaya histolytica (species)	2607	4093	-2.8
Bacteroides (genus)	232904	276348	-2.8
Oscillospira (genus)	22836	28653	-2.8
Anaerotruncus colihominis (species)	1739	2436	-2.8
Anaerotruncus (genus)	1834	2520	-2.7
Hathewaya (genus)	2618	4058	-2.7
Parabacteroides merdae (species)	7249	11459	-2.6

There is some agreement with studies on these findings, but as cited above — results are not consistent in studies.

• Fecal bacterial microbiota in constipated patients before and after eight weeks of daily Bifidobacterium infantis 35624 administration [2022] , “Oscillospira, was the taxon most strongly correlated”
• “high abundances of Prevotella,… may be the main factors in curing constipation.[2020]
• ” studies have found that Bacteroides were more abundant in colonic mucosa of patients with chronic constipation” [2017]

Interesting Enzymes

As with bacteria we had both too few and too many.

Enzyme	Reference Mean	Study Mean	Z-Score
UDP-N-acetyl-alpha-D-mannosamine:NAD+ 6-oxidoreductase (1.1.1.336)	121077	167870	-4.1
GDP-alpha-D-mannose:2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol 6-alpha-D-mannosyltransferase (configuration-retaining) (2.4.1.346)	43257	68972	-4.1
UDP-2-acetamido-3-amino-2,3-dideoxy-alpha-D-glucuronate:2-oxoglutarate aminotransferase (2.6.1.98)	44942	68064	-4.1
acetyl-CoA:UDP-2-acetamido-3-amino-2,3-dideoxy-alpha-D-glucuronate N-acetyltransferase (2.3.1.201)	67863	98332	-4
chondroitin AC lyase (4.2.2.5)	62785	90081	-3.8
alpha-N-acetyl-D-glucosaminide N-acetylglucosaminohydrolase (3.2.1.50)	170810	221135	-3.7
glycine:H-protein-lipoyllysine oxidoreductase (decarboxylating, acceptor-amino-methylating) (1.4.4.2)	188544	239012	-3.7
L-leucyl-tRNALeu:[protein] N-terminal L-lysine/L-arginine leucyltransferase (2.3.2.6)	129313	167839	-3.7
5-phospho-alpha-D-ribose 1,2-cyclic phosphate 2-phosphohydrolase (alpha-D-ribose 1,5-bisphosphate-forming) (3.1.4.55)	185457	234894	-3.7
(2E,6E)-farnesyl-diphosphate:isopentenyl-diphosphate farnesyltranstransferase (adding 5 isopentenyl units) (2.5.1.90)	195115	245998	-3.6

Enzyme	Reference Mean	Study Mean	Z-Score
propanoyl-CoA:oxaloacetate C-propanoyltransferase (thioester-hydrolysing, 1-carboxyethyl-forming) (2.3.3.5)	1509	500	5.2
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate pyruvate-lyase (succinate-forming) (4.1.3.30)	1458	500	4.9
N-succinyl-LL-2,6-diaminoheptanedioate amidohydrolase (3.5.1.18)	101418	72762	4.7
ADP-alpha-D-glucose:alpha-D-glucose-1-phosphate 4-alpha-D-glucosyltransferase (configuration-retaining) (2.4.1.342)	77187	49189	4.6
3-(cis-5,6-dihydroxycyclohexa-1,3-dien-1-yl)propanoate:NAD+ oxidoreductase (1.3.1.87)	580	183	4.5
3-phenylpropanoate,NADH:oxygen oxidoreductase (2,3-hydroxylating) (1.14.12.19)	593	189	4.4
D-tagatose 1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase (glycerone-phosphate-forming) (4.1.2.40)	89078	62686	4.4
UDP-N-acetyl-alpha-D-glucosamine:lipopolysaccharide N-acetyl-D-glucosaminyltransferase (2.4.1.56)	1077	376	4.3
D-aspartate:[beta-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n ligase (ADP-forming) (6.3.1.12)	87698	61735	4.3
penicillin amidohydrolase (3.5.1.11)	83364	57721	4.3

Bottom Line

While constipation is often assumed to be due too many of some bacteria, the evidence suggestions that not enough is the more likely cause. There appears to be no simple model or answer.

Prevotella copri will hopefully be available as a probiotic in a few year. There are two natural sources for P.Copri : Beer and Sauerkraut [2020], which may be an experiment for those that are prone to constipation..

Looking at the suggestions — Constipation caused by Antibiotics!

This is not a “new discovery” — rather it appears to confirm that the mathematic model being used is reasonable and thus Dr. Artificial Intelligence suggestions are reasonable!

This is a common symptom for many people. This is reported often in samples, and thus being examined if it reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. It does. We are not being specific about the type of allergy.

Sub-Series Study Populations:

We have 5 symptom annotations that this sub-series are examining, I tried different combination to see which resulted in a higher z-score to identify probable siblings (in a statistical sense)

• New food sensitivities – 12.1 z-score
• Medication sensitivities -8.8 z-score
  • Combined, dropped to 6.4
• Alcohol intolerance – 8.6 z-score
  • with Medication sensitivities 9.9 z-score and less bacteria
• Allergic Rhinitis (Hay Fever) – 8.6 z-score
  • When combined with any of the above, a major drop of z-scores
• Allergies – 9.2 z-score
  • With new food sensitivities – 9.9 z-score
  • When combined with any of the other, a major drop of z-scores

We have broken this down into 3 sub-groups of microbiome shifts:

• Allergies and Food Sensitivity
• Alcohol intolerance + Medication sensitivities
• Allergic Rhinitis (Hay Fever) (this study)

Symptom	Reference	Study
Allergic Rhinitis (Hay Fever)	1161	42

• Bacteria Detected with z-score > 2.6: found 222 items, highest value was 8.6
• Enzymes Detected with z-score > 2.6: found 250 items, highest value was 6.8
• Compound Detected with z-score > 2.6: found No items

Interesting Significant Bacteria

All bacteria found significant (except 1) had too low levels. This is a common pattern found with these studies, it is not “bad bacteria bogie man bacteria” but an absence of “upstanding citizens bacteria”.

The key bacteria are very different from the other two studies in this sub-series. We do see one retail level probiotic in the list: Bifidobacterium animalis (species)

Bacteria	Reference Mean	Study	Z-Score
Desulfovibrio (genus)	2770	625	8.6
Bacteroides stercoris (species)	14185	2169	7.8
Desulfovibrio simplex (species)	213	27	6.9
Phocaeicola sartorii (species)	807	276	6.4
Opitutae (class)	164	40	6.1
Actinobacillus pleuropneumoniae (species)	56	16	6
Planifilum (genus)	80	34	5.9
Planifilum fimeticola (species)	80	34	5.9
Puniceicoccaceae (family)	159	40	5.9
Cerasicoccus (genus)	313	36	5.8
Actinobacillus porcinus (species)	182	62	5.4
Veillonella (genus)	3935	1927	5.3
Desulfurispora thermophila (species)	68	35	5.3
Desulfurispora (genus)	68	35	5.3
Tepidanaerobacteraceae (family)	55	24	5.3
Thermoactinomycetaceae (family)	81	37	5.3
Rhodanobacteraceae (family)	838	249	5.3
Eggerthella sinensis (species)	179	45	5.2
Lactiplantibacillus pentosus (species)	120	25	5.2
Tepidanaerobacter (genus)	54	24	5.1
Tepidanaerobacter syntrophicus (species)	54	24	5.1
Absiella (genus)	728	74	5.1
delta/epsilon subdivisions (subphylum)	6122	3174	5.1
Veillonellales (order)	17250	11649	5
Bifidobacterium animalis (species)	1160	124	5

Looking at published studies we see many close matches, with most of the species cited in those studies being too low.

• Phocaeicola sartorii (species) <=> Phocaeicola massiliensis (NCBI:204516 )
• Bifidobacterium animalis (species) <=> Bifidobacterium (NCBI:1678 )
• Clostridium chartatabidum (species), Clostridia (class) <=> Clostridium butyricum (NCBI:1492 )
• Dialister invisus (species) <=> Dialister succinatiphilus (NCBI:487173 )

Note: This study and published studies suffer from the issues described in The taxonomy nightmare before Christmas…

Interesting Enzymes

All 250 enzymes found significant had too low levels.

Enzyme	Reference Mean	Study Mean	Z-Score
chorismate hydro-lyase (3-[(1-carboxyvinyl)oxy]benzoate-forming) (4.2.1.151)	1654	360	6.8
dolichyl-diphosphooligosaccharide:protein-L-asparagine N-beta-D-oligopolysaccharidotransferase (2.4.99.18)	1611	318	6.8
S-adenosyl-L-methionine:3-[(1-carboxyvinyl)-oxy]benzoate adenosyltransferase (HCO3–hydrolysing, 6-amino-6-deoxyfutalosine-forming) (2.5.1.120)	1624	363	6.8
dehypoxanthine futalosine:S-adenosyl-L-methionine oxidoreductase (cyclizing) (1.21.98.1)	1615	363	6.7
2-amino-3,7-dideoxy-D-threo-hept-6-ulosonate:NAD+ oxidoreductase (deaminating) (1.4.1.24)	1548	345	6.6
ATP phosphohydrolase (ABC-type, tungstate-importing) (7.3.2.6)	1378	302	6.6
hydrogen:ferricytochrome-c3 oxidoreductase (1.12.2.1)	1388	320	6.6
[TtuB sulfur-carrier protein]-Gly-NH-CH2-C(O)SH:tRNA (5-methyluridine54-2-O)-sulfurtransferase (2.8.1.15)	1359	307	6.5
isethionate sulfite-lyase (4.4.1.38)	1524	318	6.5
ATP phosphohydrolase (ABC-type, capsular-polysaccharide-exporting) (7.6.2.12)	949	239	6.5
6-amino-6-deoxyfutalosine deaminase (3.5.4.40)	1667	459	6.3
hydrogen-sulfide:[DsrC sulfur-carrier protein],acceptor oxidoreductase (1.8.99.5)	1304	323	6.2
futalosine ribohydrolase (3.2.2.26)	1241	311	6.1
siroheme carboxy-lyase (4.1.1.111)	1340	531	6
propanoyl-CoA:oxaloacetate C-propanoyltransferase (thioester-hydrolysing, 1-carboxyethyl-forming) (2.3.3.5)	1479	366	5.9
S-methyl-5′-thioadenosine:phosphate S-methyl-5-thio-alpha-D-ribosyl-transferase (2.4.2.28)	3646	1532	5.8
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate pyruvate-lyase (succinate-forming) (4.1.3.30)	1430	379	5.6
2-dehydrotetronate isomerase (5.3.1.35)	1399	447	5.4
L-threonate:NAD+ 2-oxidoreductase (1.1.1.411)	1405	446	5.3
5-aminopentanoate:2-oxoglutarate aminotransferase (2.6.1.48)	2363	797	5.2
(S)-3-amino-2-methylpropanoate:2-oxoglutarate aminotransferase (2.6.1.22)	2356	796	5.2
(2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate hydro-lyase [(Z)-but-2-ene-1,2,3-tricarboxylate-forming] (4.2.1.79)	1290	383	5.1
3-deoxy-alpha-D-manno-octulopyranosonate:oxygen 8-oxidoreductase (1.1.3.48)	699	196	5
GTP:molybdenum cofactor guanylyltransferase (2.7.7.77)	17411	9662	5
1-phosphatidyl-1D-myo-inositol-4,5-bisphosphate 4-phosphohydrolase (3.1.3.78)	1912	326	5

Bottom Line

We appear to have general agreement with published studies. The purpose of this series is to identify the shifts using a lab/analysis that is available to anyone world wide with the ability to identify the bacteria causing the issue with reliability and higher statistical significance than most studies.

This is a common symptom for many people with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This is reported often in samples, and thus being examined if it reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. It does. We are not being specific about the type of allergy.

Sub-Series Study Populations:

We have 5 symptom annotations that this sub-series are examining, I tried different combination to see which resulted in a higher z-score to identify probable siblings (in a statistical sense)

• New food sensitivities – 12.1 z-score
• Medication sensitivities -8.8 z-score
  • Combined, dropped to 6.4
• Alcohol intolerance – 8.6 z-score
  • with Medication sensitivities 8.6 z-score and less bacteria
• Allergic Rhinitis (Hay Fever) – 8.6 z-score
  • When combined with any of the above, a major drop of z-scores
• Allergies – 9.2 z-score
  • With new food sensitivities – 9.9 z-score
  • When combined with any of the other, a major drop of z-scores

We have broken this down into 3 sub-groups of microbiome shifts:

• Allergies and Food Sensitivity
• Alcohol intolerance + Medication sensitivities (this study).
• Allergic Rhinitis (Hay Fever)

Symptom	Reference	Study
Alcohol intolerance + Medication sensitivities	1144	59

• Bacteria Detected with z-score > 2.6: found 130 items, highest value was 8.6
• Enzymes Detected with z-score > 2.6: found 507 items, highest value was 7.9
• Compound Detected with z-score > 2.6: found No items

The bacteria that was most significant was NOT Prevotella copri (species) which we saw with Special Studies: Allergies And Food Sensitivity.

Interesting Significant Bacteria

All bacteria found significant (except 1) had too low levels. This is a common pattern found with these studies, it is not “bad bacteria bogie man bacteria” but an absence of “upstanding citizens bacteria”. The signature is very interesting because it is specific Bifidobacterium species — despite this, the Bifidobacterium genus was not found to be statistically significant. This drops us into the odd space of general Bifidobacterium probiotics likely not be effective, but specific strains may be(unfortunately those strains are not available as probiotics). There is one retail probiotics that contains Enterbacter, General Biotics/Equilibrium which give an experiment to try.

Bacteria	Reference Mean	Study	Z-Score
Bifidobacterium gallicum (species)	3698	136	8.6
Bifidobacterium catenulatum subsp. kashiwanohense (subspecies)	316	55	6.9
Bifidobacterium kashiwanohense PV20-2 (strain)	315	55	6.8
Enterobacter (genus)	1361	127	5.6
Bifidobacterium angulatum (species)	183	20	5.2
Gammaproteobacteria (class)	14010	5636	5
Aeromonadaceae (family)	157	25	5

Interesting Enzymes

All 507 enzymes found significant had too low levels. This places it into the same class of massive enzyme disruptions as seen in Special Studies: Depression . As with that one, apologies for the massive list — I am keeping to my practice for these studies of listing everything with 5.0 z-score or higher.

Enzyme	Reference Mean	Study Mean	Z-Score
2-acetylphloroglucinol C-acetyltransferase (2.3.1.272)	177	28	7.9
[cysteine desulfurase]-S-sulfanyl-L-cysteine:[molybdopterin-synthase sulfur-carrier protein]-Gly-Gly sulfurtransferase (2.8.1.11)	5231	1805	7.7
S-adenosyl-L-methionine:tellurite methyltransferase (2.1.1.265)	5238	1938	7
decenoyl-[acyl-carrier protein] Delta2-trans-Delta3-cis-isomerase (5.3.3.14)	6010	2276	6.9
tRNA-uridine65 uracil mutase (5.4.99.26)	4052	1226	6.8
coproporphyrinogen:oxygen oxidoreductase (decarboxylating) (1.3.3.3)	3163	746	6.8
donor:hydrogen-peroxide oxidoreductase (1.11.1.21)	3030	672	6.7
2-(1,2-epoxy-1,2-dihydrophenyl)acetyl-CoA isomerase (5.3.3.18)	3097	1059	6.7
3-hydroxybutanoyl-CoA 3-epimerase (5.1.2.3)	2951	696	6.7
ATP:nicotinamide-nucleotide adenylyltransferase (2.7.7.1)	5076	2200	6.7
ATP:1-(beta-D-ribofuranosyl)-nicotinamide 5′-phosphotransferase (2.7.1.22)	5025	2187	6.6
isocitrate glyoxylate-lyase (succinate-forming) (4.1.3.1)	2955	730	6.6
D-amino acid:quinone oxidoreductase (deaminating) (1.4.5.1)	2485	686	6.5
L-methionine:2-oxo-acid aminotransferase (2.6.1.88)	2759	652	6.5
2-(glutathione-S-yl)-hydroquinone:glutathione oxidoreductase (1.8.5.7)	3140	748	6.5
D-glucose:ubiquinone oxidoreductase (1.1.5.2)	2200	462	6.5
methanesulfonate,FMNH2:oxygen oxidoreductase (1.14.14.34)	2239	489	6.5
alkanesulfonate,FMNH2:oxygen oxidoreductase (1.14.14.5)	2239	489	6.5
glutathione:NADP+ oxidoreductase (1.8.1.7)	5947	2494	6.5
triphosphate phosphohydrolase (3.6.1.25)	4494	2012	6.4
S-(hydroxymethyl)glutathione:NAD+ oxidoreductase (1.1.1.284)	2862	759	6.4
(S)-3-hydroxyacyl-CoA:NAD+ oxidoreductase (1.1.1.35)	3374	926	6.4
ferredoxin:NAD+ oxidoreductase (1.18.1.3)	1992	455	6.4
acyl-CoA:sn-glycerol-3-phosphate 1-O-acyltransferase (2.3.1.15)	3270	1139	6.4
S-adenosyl-L-methionine:tRNA (cytidine32/uridine32-2′-O)-methyltransferase (2.1.1.200)	3316	1093	6.3
[50S ribosomal protein L16]-L-Arg81,2-oxoglutarate:oxygen oxidoreductase (3R-hydroxylating) (1.14.11.47)	3334	1114	6.3
choline:acceptor 1-oxidoreductase (1.1.99.1)	2748	562	6.3
acetyl-CoA:glyoxylate C-acetyltransferase [(S)-malate-forming] (2.3.3.9)	3116	950	6.3
siroheme ferro-lyase (sirohydrochlorin-forming) (4.99.1.4)	2565	539	6.2
deoxyribocyclobutadipyrimidine pyrimidine-lyase (4.1.99.3)	4156	1337	6.2
acetyl-CoA:[elongator tRNAMet]-cytidine34 N4-acetyltransferase (ATP-hydrolysing) (2.3.1.193)	3309	1094	6.2
7,8-dihydroneopterin 3′-triphosphate diphosphohydrolase (3.6.1.67)	3607	1299	6.2
n/a (3.4.11.23)	3312	1083	6.2
acetyl-CoA:dTDP-4-amino-4,6-dideoxy-alpha-D-galactose N-acetyltransferase (2.3.1.210)	2766	673	6.2
ATP:N-acetyl-D-glucosamine 6-phosphotransferase (2.7.1.59)	3263	1071	6.2
L-2,4-diaminobutanoate carboxy-lyase (propane-1,3-diamine-forming) (4.1.1.86)	2127	304	6.2
chorismate pyruvate-lyase (4-hydroxybenzoate-forming) (4.1.3.40)	2596	567	6.2
protein dithiol:quinone oxidoreductase (disulfide-forming) (1.8.5.9)	3557	1276	6.2
fatty acyl-[acyl-carrier protein]:alpha-Kdo-(2->4)-alpha-Kdo-(2->6)-(acyl)-[lipid IVA] O-acyltransferase (2.3.1.243)	3322	1097	6.2
ATP:L-threonine O3-phosphotransferase (2.7.1.177)	2358	350	6.1
ditrans-octacis-undecaprenyl-diphosphate:alpha-D-Kdo-(2->4)-alpha-D-Kdo-(2->6)-lipid-A phosphotransferase (2.7.4.29)	2852	1008	6.1
D-sorbitol-6-phosphate:NAD+ 2-oxidoreductase (1.1.1.140)	2447	677	6.1
diacylglycerol-3-phosphate phosphohydrolase (3.1.3.4)	3284	1105	6.1
1,2-diacyl-sn-glycerol 3-phosphate phosphohydrolase (3.1.3.81)	3284	1105	6.1
(R)-lactate:quinone 2-oxidoreductase (1.1.5.12)	2328	510	6.1
(S)-lactate:ferricytochrome-c 2-oxidoreductase (1.1.2.3)	2368	544	6.1
methyl DNA-base, 2-oxoglutarate:oxygen oxidoreductase (formaldehyde-forming) (1.14.11.33)	2304	475	6.1
ATP:D-ribulose-5-phosphate 1-phosphotransferase (2.7.1.19)	2435	543	6.1
(2S,3S)-2,3-dihydro-2,3-dihydroxybenzoate:NAD+ oxidoreductase (1.3.1.28)	2240	476	6.1
D-mannitol-1-phosphate:NAD+ 5-oxidoreductase (1.1.1.17)	2672	727	6
2-O-(alpha-D-mannopyranosyl)-D-glycerate D-mannohydrolase (3.2.1.170)	1248	396	6
S-formylglutathione hydrolase (3.1.2.12)	2402	554	6
gamma-L-glutamyl-L-cysteinyl-glycine:spermidine amidase (3.5.1.78)	3189	1059	6
gamma-L-glutamyl-L-cysteinyl-glycine:spermidine ligase (ADP-forming) [spermidine is numbered so that atom N-1 is in the amino group of the aminopropyl part of the molecule] (6.3.1.8)	3189	1059	6
S-adenosyl-L-methionine:23S rRNA (uracil747-C5)-methyltransferase (2.1.1.189)	3257	1112	6
S-adenosyl-L-methionine:uridine in tRNA 3-[(3S)-3-amino-3-carboxypropyl]transferase (2.5.1.25)	1704	303	6
succinate-semialdehyde:NAD+ oxidoreductase (1.2.1.24)	2416	449	6
Fe(II)-siderophore:NADP+ oxidoreductase (1.16.1.9)	2344	447	6
ATP phosphohydrolase (ABC-type, taurine-importing) (7.6.2.7)	2185	521	6
geraniol:NADP+ oxidoreductase (1.1.1.183)	2470	466	6
ATP:N-acyl-D-mannosamine 6-phosphotransferase (2.7.1.60)	3204	1098	5.9
L-serine:[L-seryl-carrier protein] ligase (AMP-forming) (6.2.1.72)	2199	454	5.9
galactarate hydro-lyase (5-dehydro-4-deoxy-D-glucarate-forming) (4.2.1.42)	3015	963	5.9
propanoyl-CoA:phosphate propanoyltransferase (2.3.1.222)	1738	358	5.9
ATP:thiamine phosphotransferase (2.7.1.89)	2372	492	5.9
ATP phosphohydrolase (ABC-type, putrescine-importing) (7.6.2.16)	2302	503	5.9
ubiquinol:oxygen oxidoreductase (superoxide-forming) (1.10.3.17)	2232	475	5.9
S-adenosyl-L-methionine:23S rRNA (guanine1835-N2)-methyltransferase (2.1.1.174)	2258	485	5.9
riboflavin:NAD(P)+ oxidoreductase (1.5.1.41)	2323	491	5.9
D-erythrose 4-phosphate:NAD+ oxidoreductase (1.2.1.72)	2267	485	5.9
CDP-diacylglycerol phosphatidylhydrolase (3.6.1.26)	2239	499	5.9
D-glucarate hydro-lyase (5-dehydro-4-deoxy-D-glucarate-forming) (4.2.1.40)	2953	1125	5.9
6-phospho-D-gluconate hydro-lyase (2-dehydro-3-deoxy-6-phospho-D-gluconate-forming) (4.2.1.12)	2260	495	5.8
ATP:propanoate phosphotransferase (2.7.2.15)	2215	469	5.8
isochorismate pyruvate-hydrolase (3.3.2.1)	2164	473	5.8
(3Z/3E)-alk-3-enoyl-CoA (2E)-isomerase (5.3.3.8)	2225	487	5.8
ATP phosphohydrolase (ABC-type, L-arabinose-importing) (7.5.2.12)	2214	473	5.8
n/a (3.4.24.55)	2279	492	5.8
diacylphosphatidylethanolamine:alpha-D-Kdo-(2->4)-alpha-D-Kdo-(2->6)-lipid-A 7”-phosphoethanolaminetransferase (2.7.8.42)	2371	500	5.8
2,3-dihydroxybenzoate:L-serine ligase (6.3.2.14)	2179	611	5.8
2-O-(alpha-D-glucopyranosyl)-D-glycerate:phosphate alpha-D-glucosyltransferase (configuration-retaining) (2.4.1.352)	1217	249	5.8
pyrimidine-5′-nucleotide phosphoribo(deoxyribo)hydrolase (3.2.2.10)	2222	495	5.8
6-sulfo-alpha-D-quinovosyl diacylglycerol 6-sulfo-D-quinovohydrolase (3.2.1.199)	1113	222	5.8
(9Z)-hexadec-9-enoyl-[acyl-carrier protein]:Kdo2-lipid IVA O-palmitoleoyltransferase (2.3.1.242)	2356	502	5.8
[RNA]-adenosine-cytidine 5′-hydroxy-adenosoine ribonucleotide-3′-[RNA fragment]-lyase (cyclicizing; [RNA fragment]-3′-cytidine-2′,3′-cyclophosphate-forming and hydrolysing) (4.6.1.21)	2312	470	5.8
ATP phosphohydrolase (ABC-type, D-allose-importing) (7.5.2.8)	2146	431	5.8
6-methoxy-3-methyl-2-(all-trans-polyprenyl)-1,4-benzoquinol,acceptor:oxygen oxidoreductase (5-hydroxylating) (1.14.99.60)	2180	540	5.8
NADPH:NAD+ oxidoreductase (Si-specific) (1.6.1.1)	2204	490	5.8
taurine, 2-oxoglutarate:oxygen oxidoreductase (sulfite-forming) (1.14.11.17)	2122	496	5.8
(deoxy)cytidine 5′-triphosphate diphosphohydrolase (3.6.1.65)	2307	500	5.7
2-(all-trans-polyprenyl)phenol,NADPH:oxygen oxidoreductase (6-hydroxylating) (1.14.13.240)	2178	535	5.7
dTDP-N-acetyl-alpha-D-fucose:N-acetyl-beta-D-mannosaminouronyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol N-acetylfucosaminyltransferase (2.4.1.325)	2308	507	5.7
ATP:[isocitrate dehydrogenase (NADP+)] phosphotransferase (2.7.11.5)	2142	516	5.7
2,3-dihydroxybenzoate:[aryl-carrier protein] ligase (AMP-forming) (6.2.1.71)	2118	604	5.7
5,6,7,8-tetrahydromonapterin:NADP+ oxidoreductase (1.5.1.50)	2159	476	5.7
glutathione gamma-glutamyl cyclotransferase (5-oxo-L-proline producing) (4.3.2.7)	2158	500	5.7
iron(III)-enterobactin hydrolase (3.1.1.108)	2204	491	5.7
N,N’-diacetylchitobiose acetylhydrolase (3.5.1.105)	2304	508	5.7
N-succinyl-L-glutamate amidohydrolase (3.5.1.96)	2172	518	5.7
protein-Npi-phospho-L-histidine:N-acetyl-D-muramate Npi-phosphotransferase (2.7.1.192)	2283	474	5.7
4-alpha-D-[(1->4)-alpha-D-glucano]trehalose glucanohydrolase (trehalose-producing) (3.2.1.141)	1335	181	5.7
acetyl-CoA:N6-hydroxy-L-lysine 6-acetyltransferase (2.3.1.102)	708	159	5.6
4-aminobutanoate:2-oxoglutarate aminotransferase (2.6.1.19)	3600	1155	5.6
ATP:(S)-4,5-dihydroxypentane-2,3-dione 5-phosphotransferase (2.7.1.189)	1415	220	5.6
inosine/xanthosine 5′-triphosphate phosphohydrolase (3.6.1.73)	2071	496	5.6
6-deoxy-6-sulfofructose-1-phosphate 2-hydroxy-3-oxopropane-1-sulfonate-lyase (glycerone-phosphate-forming) (4.1.2.57)	1346	295	5.6
protein-Npi-phospho-L-histidine:2-O-alpha-mannopyranosyl-D-glycerate Npi-phosphotransferase (2.7.1.195)	1163	234	5.6
2,3-dihydroxypropane-1-sulfonate:NAD+ 3-oxidoreductase (1.1.1.373)	1341	295	5.6
4-aminobutanal:NAD+ 1-oxidoreductase (1.2.1.19)	2237	491	5.6
N-succinyl-L-glutamate 5-semialdehyde:NAD+ oxidoreductase (1.2.1.71)	2135	535	5.6
protein-dithiol:NAD(P)+ oxidoreductase (1.8.1.8)	2151	540	5.6
succinyl-CoA:acetyl-CoA C-succinyltransferase (2.3.1.174)	1445	205	5.6
succinyl-CoA:L-arginine N2-succinyltransferase (2.3.1.109)	2135	536	5.6
3-oxo-5,6-dehydrosuberyl-CoA semialdehyde:NADP+ oxidoreductase (1.2.1.91)	1461	221	5.6
2-oxepin-2(3H)-ylideneacetyl-CoA hydrolase (3.3.2.12)	1461	221	5.6
N2-succinyl-L-arginine iminohydrolase (decarboxylating) (3.5.3.23)	2134	536	5.6
ATP phosphohydrolase (ABC-type, nitrate-importing) (7.3.2.4)	1523	142	5.6
7,8-dihydroneopterin 3′-triphosphate 2′-epimerase (5.1.99.7)	1928	468	5.5
N4-acetylcytidine amidohydrolase (3.5.1.135)	2966	1096	5.5
N2-succinyl-L-ornithine:2-oxoglutarate 5-aminotransferase (2.6.1.81)	2254	677	5.5
(1->4)-alpha-D-glucan 1-alpha-D-glucosylmutase (5.4.99.15)	1319	183	5.5
ATP:2-dehydro-3-deoxy-D-galactonate 6-phosphotransferase (2.7.1.58)	1536	299	5.5
2-dehydro-3-deoxy-6-phospho-D-galactonate D-glyceraldehyde-3-phospho-lyase (pyruvate-forming) (4.1.2.21)	1538	299	5.5
(S)-ureidoglycolate:NAD+ oxidoreductase (1.1.1.350)	1729	436	5.5
ATP:D-glyceraldehyde 3-phosphotransferase (2.7.1.28)	1512	115	5.5
ATP:glycerone phosphotransferase (2.7.1.29)	1512	115	5.5
FAD AMP-lyase (riboflavin-cyclic-4′,5′-phosphate-forming) (4.6.1.15)	1512	115	5.5
tRNA 2-(methylsulfanyl)-N6-prenyladenosine37,donor:oxygen 4-oxidoreductase (trans-hydroxylating) (1.14.99.69)	1565	158	5.5
S-methyl-5′-thioadenosine:phosphate S-methyl-5-thio-alpha-D-ribosyl-transferase (2.4.2.28)	3673	1543	5.4
primary-amine:oxygen oxidoreductase (deaminating) (1.4.3.21)	1495	217	5.4
UDP-4-amino-4-deoxy-alpha-L-arabinose:ditrans,octacis-undecaprenyl phosphate 4-amino-4-deoxy-alpha-L-arabinosyltransferase (2.4.2.53)	2107	573	5.4
(2S)-2-hydroxy-3,4-dioxopentyl phosphate aldose-ketose-isomerase (5.3.1.32)	1529	259	5.4
acyl-CoA:acetyl-CoA C-acyltransferase (2.3.1.16)	3869	1876	5.4
2,3-didehydroadipoyl-CoA:acetyl-CoA C-didehydroadipoyltransferase (double bond migration) (2.3.1.223)	1516	224	5.4
10-formyltetrahydrofolate:UDP-4-amino-4-deoxy-beta-L-arabinose N-formyltransferase (2.1.2.13)	2048	470	5.4
UDP-alpha-D-glucuronate:NAD+ oxidoreductase (decarboxylating) (1.1.1.305)	2048	470	5.4
4-amino-4-deoxy-alpha-L-arabinopyranosyl ditrans,octacis-undecaprenyl-phosphate:lipid IVA 4-amino-4-deoxy-L-arabinopyranosyltransferase (2.4.2.43)	2044	473	5.4
5-(methylsulfanyl)-D-ribulose-1-phosphate 4-hydro-lyase [5-(methylsulfanyl)-2,3-dioxopentyl-phosphate-forming] (4.2.1.109)	1552	181	5.3
UDP-4-amino-4-deoxy-beta-L-arabinose:2-oxoglutarate aminotransferase (2.6.1.87)	2070	480	5.3
phenylacetyl-CoA:oxygen oxidoreductase (1,2-epoxidizing) (1.14.13.149)	1375	278	5.3
ATP phosphohydrolase (ABC-type, D-xylose-transporting) (7.5.2.10)	1473	308	5.3
5-(methylsulfanyl)-2,3-dioxopentyl-phosphate phosphohydrolase (isomerizing) (3.1.3.77)	1689	121	5.3
N-benzoylamino-acid amidohydrolase (3.5.1.32)	1712	408	5.3
phenylacetaldehyde:NAD+ oxidoreductase (1.2.1.39)	1391	271	5.3
L-glutamate:putrescine ligase (ADP-forming) (6.3.1.11)	1902	448	5.3
iron(III)-salmochelin complex hydrolase (3.1.1.109)	727	159	5.3
2-O-(alpha-D-mannosyl)-3-phosphoglycerate phosphohydrolase (3.1.3.70)	2061	498	5.3
4-(gamma-L-glutamylamino)butanoate amidohydrolase (3.5.1.94)	1914	445	5.3
GDP-alpha-D-mannuronate:mannuronan D-mannuronatetransferase (2.4.1.33)	154	39	5.2
[mannuronan]-beta-D-mannuronate 5-epimerase (5.1.3.37)	154	39	5.2
3-(indol-3-yl)pyruvate carboxy-lyase [(2-indol-3-yl)acetaldehyde-forming] (4.1.1.74)	1802	138	5.2
quinate:quinol 3-oxidoreductase (1.1.5.8)	1523	124	5.2
betaine-aldehyde:NAD+ oxidoreductase (1.2.1.8)	2057	434	5.2
catechol:oxygen 2,3-oxidoreductase (ring-opening) (1.13.11.2)	3240	1416	5.2
1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-3-one:oxygen oxidoreductase (formate- and CO-forming) (1.13.11.53)	1714	283	5.2
1,2-dihydroxy-5-(methylsulfanyl)pent-1-en-3-one:oxygen oxidoreductase (formate-forming) (1.13.11.54)	1714	283	5.2
ATP phosphohydrolase (ABC-type, thiamine-importing) (7.6.2.15)	3503	1300	5.2
citrate:N6-acetyl-N6-hydroxy-L-lysine ligase (AMP-forming) (6.3.2.38)	797	193	5.1
RX:glutathione R-transferase (2.5.1.18)	2968	1025	5.1
N2-citryl-N6-acetyl-N6-hydroxy-L-lysine:N6-acetyl-N6-hydroxy-L-lysine ligase (AMP-forming) (6.3.2.39)	795	193	5.1
putrescine:2-oxoglutarate aminotransferase (2.6.1.82)	3168	1490	5.1
UDP-alpha-D-glucose:enterobactin 5′-C-beta-D-glucosyltransferase (configuration-inverting) (2.4.1.369)	807	200	5.1
4-hydroxybutanoate:NAD+ oxidoreductase (1.1.1.61)	2322	607	5.1
D-xylonate hydro-lyase (2-dehydro-3-deoxy-D-arabinonate-forming) (4.2.1.82)	621	178	5
D-glycerate:NAD(P)+ oxidoreductase (1.1.1.60)	1888	516	5
galactitol-1-phosphate:NAD+ oxidoreductase (1.1.1.251)	997	277	5
alkylmercury mercury(II)-lyase (alkane-forming) (4.99.1.2)	577	115	5
(S)-2-hydroxyglutarate:quinone oxidoreductase (1.1.5.13)	2192	670	5
(R)-3-hydroxyacyl-CoA:NADP+ oxidoreductase (1.1.1.36)	523	154	5

Bottom Line

These two symptoms tend to be ignored by the medical establishment. There are studies on the microbiome impacting the efficiency of prescription drugs but not sensitivities or hyper-reactivity. This means that this post is likely the first study on these in existence.

Social Thread

This is a common symptom for many people. This is reported often in samples, and thus being examined if it reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. It does. We are not being specific about the type of allergy.

Sub-Series Study Populations:

We have 5 symptom annotations that this sub-series are examining, I tried different combination to see which resulted in a higher z-score to identify probable siblings (in a statistical sense)

• New food sensitivities – 12.1 z-score
• Medication sensitivities -8.8 z-score
  • Combined, dropped to 6.4
• Alcohol intolerance – 8.6 z-score
  • with Medication sensitivities 9.9 z-score and less bacteria
• Allergic Rhinitis (Hay Fever) – 8.6 z-score
  • When combined with any of the above, a major drop of z-scores
• Allergies – 9.2 z-score
  • With new food sensitivities – 9.9 z-score
  • When combined with any of the other, a major drop of z-scores

We have broken this down into 3 sub-groups of microbiome shifts:

• Allergies and Food Sensitivity (this study).
• Alcohol intolerance + Medication sensitivities
• Allergic Rhinitis (Hay Fever)

Symptom	Reference	Study
Allergies And Food Sensitivity	1130	73

• Bacteria Detected with z-score > 2.6: found 163 items, highest value was 9.9
• Enzymes Detected with z-score > 2.6: found 364 items, highest value was 6.8
• Compound Detected with z-score > 2.6: found No items

The bacteria that was most significant was Prevotella copri (species) which seems to occur often in these special studies.

Interesting Significant Bacteria

All bacteria found significant (except 1) had too low levels. This is a common pattern found with these studies, it is not “bad bacteria bogie man bacteria” but an absence of “upstanding citizens bacteria”. What is very striking is that with allergies, Prevotella copri is 1/10 that of the reference population, but as you move up to it’s genus (Prevotella) and family (Prevotellaceae) the ratio becomes less and less extreme. The species is where things are happening. There is one retail probiotic species listed (E.Coli – i.e. Mutaflor or Symbioflor-2) and two Bifidobacterium species which hopefully will become available one day.

” Since its discovery in 2007, the importance of the human gut bacterium Prevotella copri (P. copri) has been widely recognized with its links to diet and health status and potential as next generation probiotic” [2021]

Bacteria	Reference Mean	Study	Z-Score
Prevotella copri (species)	66190	6097	9.9
Shuttleworthia (genus)	279	61	6.9
Prevotella (genus)	73487	24101	6.2
Tepidanaerobacter (genus)	55	25	6.2
Tepidanaerobacter syntrophicus (species)	55	25	6.2
Tepidanaerobacteraceae (family)	55	25	6.2
Prevotellaceae (family)	81231	33160	5.8
Sporolactobacillaceae (family)	174	60	5.7
Sporolactobacillus (genus)	176	62	5.6
Sporolactobacillus putidus (species)	176	62	5.6
Thermosediminibacterales (order)	53	18	5.6
Bifidobacterium catenulatum subsp. kashiwanohense (subspecies)	322	89	5.6
Bifidobacterium kashiwanohense PV20-2 (strain)	321	89	5.6
Caldilineaceae (family)	91	37	5.4
Caldilinea (genus)	91	37	5.4
Caldilineales (order)	91	37	5.4
Caldilinea tarbellica (species)	91	37	5.4
Caldilineae (class)	91	37	5.4
Lactiplantibacillus pentosus (species)	119	22	5.3
Escherichia (genus)	6123	1549	5.1

Prevotella copri is called out in several studies

• Metagenome-wide association of gut microbiome features in children with moderate-severe house dust mite allergic rhinitis [2022]
• Altered Gut Microbiota Diversity and Composition in Chronic Urticaria. [2019]
• Microbial signature in IgE-mediated food allergies. [2020]

Interesting Enzymes

All enzymes (except 3) found significant had too low levels. Given 364 items and 99% confidence, 3 is what you would expect with False Detection Rate, so we can dismiss these one.

Enzyme	Reference Mean	Study Mean	Z-Score
propanoyl-CoA:oxaloacetate C-propanoyltransferase (thioester-hydrolysing, 1-carboxyethyl-forming) (2.3.3.5)	1513	369	6.8
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate pyruvate-lyase (succinate-forming) (4.1.3.30)	1461	369	6.5
(2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate hydro-lyase [(Z)-but-2-ene-1,2,3-tricarboxylate-forming] (4.2.1.79)	1317	385	6
S-methyl-5′-thioadenosine:phosphate S-methyl-5-thio-alpha-D-ribosyl-transferase (2.4.2.28)	3705	1541	5.9
L-carnitinyl-CoA hydro-lyase [(E)-4-(trimethylammonio)but-2-enoyl-CoA-forming] (4.2.1.149)	1472	346	5.6
5-aminopentanoate:2-oxoglutarate aminotransferase (2.6.1.48)	2407	793	5.6
(S)-3-amino-2-methylpropanoate:2-oxoglutarate aminotransferase (2.6.1.22)	2400	790	5.6
2-dehydrotetronate isomerase (5.3.1.35)	1424	528	5.5
n/a (3.4.23.49)	1333	354	5.5
L-threonate:NAD+ 2-oxidoreductase (1.1.1.411)	1430	527	5.5
glutarate, 2-oxoglutarate:oxygen oxidoreductase ((S)-2-hydroxyglutarate-forming) (1.14.11.64)	1319	340	5.5
(R)-lactate hydro-lyase (4.2.1.130)	1584	348	5.4
L-carnitine,NAD(P)H:oxygen oxidoreductase (trimethylamine-forming) (1.14.13.239)	1212	333	5.4
UDP-N-acetyl-alpha-D-glucosamine:lipopolysaccharide N-acetyl-D-glucosaminyltransferase (2.4.1.56)	1094	293	5.3
protein-Npi-phospho-L-histidine:D-mannitol Npi-phosphotransferase (2.7.1.197)	72060	43158	5.3
acyl-CoA,ferrocytochrome b5:oxygen oxidoreductase (6,7 cis-dehydrogenating) (1.14.19.3)	1088	316	5.3
2,4,6/3,5-pentahydroxycyclohexanone 2-isomerase (5.3.99.11)	89479	62562	5.3
ATP:L-threonine O3-phosphotransferase (2.7.1.177)	2381	463	5.2
alpha-maltose-6′-phosphate 6-phosphoglucohydrolase (3.2.1.122)	72165	44303	5.1
2-acetylphloroglucinol C-acetyltransferase (2.3.1.272)	179	63	5.1
L-carnitine:CoA ligase (AMP-forming) (6.2.1.48)	1387	572	5.1
RNA-3′-phosphate:RNA ligase (cyclizing, AMP-forming) (6.5.1.4)	1232	371	5.1
D-serine ammonia-lyase (pyruvate-forming) (4.3.1.18)	70096	42804	5
(E)-4-(trimethylammonio)but-2-enoyl-CoA:L-carnitine CoA-transferase (2.8.3.21)	1397	563	5
gamma-butyrobetainyl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase (1.3.8.13)	1411	566	5
3-dehydro-4-phosphotetronate carboxy-lyase (4.1.1.104)	1698	647	5

Bottom Line

There is an excellent article on different strains and how they are related to diet with discussion of KEGG Enzymes, Distinct Genetic and Functional Traits of Human Intestinal Prevotella copri Strains Are Associated with Different Habitual Diets [2021] which states ” Interestingly, Italian V and VG clustered with Western populations, suggesting that a Western plant-based diet is still not effective in establishing a P. copri strain consortium typical of a traditional agrarian diet, and supporting the existence of a geographically based distribution of different strain patterns” — which hints how a change of diet is causing an uptick in allergies.

” Prevotella copri is a bacterium naturally present .. in sauerkraut and beer.” [2020] So the German Beer Hall Diet!! 😉

This is a common symptom for our times, especially with climate change and politics in some places. This is reported often in samples, and thus being examined if it reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. It does.

Depression is likely a part of a feedback loop — depression chemicals modify the microbiome resulting in more depression triggering chemicals being released.

Study Populations:

We have 2 symptom annotations that could be included

• General: Depression
• Official Diagnosis: Depression

Taking the first two together we get 85 samples with an max z-score of 5.7

Symptom	Reference	Study
High Anxiety and Anxiety/tension	1149	85

• Bacteria Detected with z-score > 2.6: found 156 items, highest value was 7.8
• Enzymes Detected with z-score > 2.6: found 508 items, highest value was 8.3
• Compound Detected with z-score > 2.6: found No items

This hints that the enzymes being produced are likely more significant than the bacteria and the number of enzymes found significant is slightly overwhelming! (I dare not say depressing)

Interesting Significant Bacteria

All bacteria found significant (except 2) had too low levels. These two are almost expected as the false detection rate, so we can likely exclude them. This is a common pattern found with these studies, it is not “bad bacteria bogie man bacteria” but an absence of “upstanding citizens bacteria”.

Bacteria	Reference Mean	Study	Z-Score
Shuttleworthia (genus)	273	42	7.8
Actinobacillus (genus)	339	80	6.6
Actinobacillus porcinus (species)	181	48	6
Haemophilus (genus)	1598	425	5.9
Haemophilus parainfluenzae (species)	1598	424	5.9
Pasteurellaceae (family)	1973	534	5.8
Pasteurellales (order)	1973	534	5.8
Pasteurellaceae incertae sedis (norank)	143	43	5.8
[Pasteurella] aerogenes-[Pasteurella] mairii-[Actinobacillus] rossii complex (species group)	143	43	5.8
Legionellaceae (family)	80	40	5.7
Legionella (genus)	80	40	5.7
[Actinobacillus] rossii (species)	143	46	5.6
Legionellales (order)	81	43	5.2
Thiobacillus thiophilus (species)	81	24	5.2
Veillonella dispar (species)	823	59	5.1
Thiobacillaceae (family)	81	25	5
Thiobacillus (genus)	80	25	5

Similar findings have been reported in some studies, for example: low Haemophilus, Pasteurellaceae, uncultured_Veillonellaceae_bacterium reported in Gut Microbiome Composition Associated With Major Depressive Disorder and Sleep Quality [2021].

Interesting Enzymes

All 508 enzymes found significant, had too low levels. Excuse the long list, but my practice has been to list everything with a z-score over 5.0; there are a lot with depression.

Enzyme	Reference Mean	Study Mean	Z-Score
[cysteine desulfurase]-S-sulfanyl-L-cysteine:[molybdopterin-synthase sulfur-carrier protein]-Gly-Gly sulfurtransferase (2.8.1.11)	5236	1517	8.3
tRNA-uridine65 uracil mutase (5.4.99.26)	4059	971	7.6
deoxyribocyclobutadipyrimidine pyrimidine-lyase (4.1.99.3)	4156	1179	6.8
acyl-CoA:sn-glycerol-3-phosphate 1-O-acyltransferase (2.3.1.15)	3270	976	6.7
7,8-dihydroneopterin 3′-triphosphate diphosphohydrolase (3.6.1.67)	3609	1084	6.6
(1->4)-alpha-D-galacturonan lyase (4.2.2.2)	2352	706	6.4
N4-acetylcytidine amidohydrolase (3.5.1.135)	2970	842	6.4
diacylglycerol-3-phosphate phosphohydrolase (3.1.3.4)	3287	920	6.3
1,2-diacyl-sn-glycerol 3-phosphate phosphohydrolase (3.1.3.81)	3287	920	6.3
acetyl-CoA:[elongator tRNAMet]-cytidine34 N4-acetyltransferase (ATP-hydrolysing) (2.3.1.193)	3309	938	6.3
S-adenosyl-L-methionine:tRNA (cytidine32/uridine32-2′-O)-methyltransferase (2.1.1.200)	3312	963	6.3
S-adenosyl-L-methionine:23S rRNA (uracil747-C5)-methyltransferase (2.1.1.189)	3260	931	6.3
protein dithiol:quinone oxidoreductase (disulfide-forming) (1.8.5.9)	3555	1117	6.3
ATP phosphohydrolase (ABC-type, thiamine-importing) (7.6.2.15)	3506	973	6.2
ATP:(Kdo)-lipid IVA 3-deoxy-alpha-D-manno-oct-2-ulopyranose 4-phosphotransferase (2.7.1.166)	1514	380	6.2
[50S ribosomal protein L16]-L-Arg81,2-oxoglutarate:oxygen oxidoreductase (3R-hydroxylating) (1.14.11.47)	3328	978	6.2
D-glucarate hydro-lyase (5-dehydro-4-deoxy-D-glucarate-forming) (4.2.1.40)	2958	997	6.1
ATP:N-acetyl-D-glucosamine 6-phosphotransferase (2.7.1.59)	3257	947	6.1
fatty acyl-[acyl-carrier protein]:alpha-Kdo-(2->4)-alpha-Kdo-(2->6)-(acyl)-[lipid IVA] O-acyltransferase (2.3.1.243)	3318	960	6.1
[RNA] 5′-hydroxy-ribonucleotide-3′-[RNA fragment]-lyase (cyclicizing; [RNA fragment]-3′- nucleoside-2′,3′-cyclophosphate-forming and hydrolysing) (4.6.1.19)	1515	390	6.1
ATP:N-acyl-D-mannosamine 6-phosphotransferase (2.7.1.60)	3204	932	6.1
n/a (3.4.11.23)	3305	966	6.1
coproporphyrinogen:oxygen oxidoreductase (decarboxylating) (1.3.3.3)	3153	824	6.1
D-amino acid:quinone oxidoreductase (deaminating) (1.4.5.1)	2484	681	6.1
gamma-L-glutamyl-L-cysteinyl-glycine:spermidine amidase (3.5.1.78)	3185	940	6
gamma-L-glutamyl-L-cysteinyl-glycine:spermidine ligase (ADP-forming) [spermidine is numbered so that atom N-1 is in the amino group of the aminopropyl part of the molecule] (6.3.1.8)	3185	940	6
CMP-N-acetyl-beta-neuraminate:beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-R (2->3)-N-acetyl-alpha-neuraminyltransferase (configuration-inverting) (2.4.99.6)	1603	406	6
galactarate hydro-lyase (5-dehydro-4-deoxy-D-glucarate-forming) (4.2.1.42)	3014	886	5.9
methanesulfonate,FMNH2:oxygen oxidoreductase (1.14.14.34)	2237	511	5.9
alkanesulfonate,FMNH2:oxygen oxidoreductase (1.14.14.5)	2237	511	5.9
donor:hydrogen-peroxide oxidoreductase (1.11.1.21)	3019	797	5.8
D-glucose:ubiquinone oxidoreductase (1.1.5.2)	2196	497	5.8
glutathione:hydroperoxide oxidoreductase (1.11.1.27)	1753	413	5.8
3-hydroxybutanoyl-CoA 3-epimerase (5.1.2.3)	2940	826	5.7
acetyl-CoA:glyoxylate C-acetyltransferase [(S)-malate-forming] (2.3.3.9)	3109	993	5.7
L-methionine:2-oxo-acid aminotransferase (2.6.1.88)	2749	745	5.7
S-adenosyl-L-methionine:23S rRNA (guanine2069-N7)-methyltransferase (2.1.1.264)	5685	2608	5.7
ferredoxin:NAD+ oxidoreductase (1.18.1.3)	1990	481	5.6
choline:acceptor 1-oxidoreductase (1.1.99.1)	2739	655	5.6
n/a (3.1.25.1)	1543	442	5.5
isocitrate glyoxylate-lyase (succinate-forming) (4.1.3.1)	2942	859	5.5
acetyl-CoA:dTDP-4-amino-4,6-dideoxy-alpha-D-galactose N-acetyltransferase (2.3.1.210)	2762	745	5.5
(S)-3-hydroxyacyl-CoA:NAD+ oxidoreductase (1.1.1.35)	3361	1073	5.5
N-acyl-D-amino acid amidohydrolase (3.5.1.81)	1787	412	5.4
2-(glutathione-S-yl)-hydroquinone:glutathione oxidoreductase (1.8.5.7)	3124	916	5.4
S-(hydroxymethyl)glutathione:NAD+ oxidoreductase (1.1.1.284)	2850	892	5.3
succinyl-CoA:3-oxo-acid CoA-transferase (2.8.3.5)	1306	319	5.3
n/a (3.4.23.51)	5016	2311	5.3
L-2,4-diaminobutanoate carboxy-lyase (propane-1,3-diamine-forming) (4.1.1.86)	2120	382	5.3
formate:[oxidized hydrogenase] oxidoreductase (1.17.98.4)	5990	2916	5.3
S-methyl-5-thio-D-ribulose 1-phosphate 1,3-isomerase (5.3.3.23)	1135	95	5.1
RX:glutathione R-transferase (2.5.1.18)	2961	1021	5.1
n/a (3.4.24.74)	4279	1132	5.1
gamma-L-glutamyl-L-cysteine:glycine ligase (ADP-forming) (6.3.2.3)	2808	901	5.1
D-glucose:NAD(P)+ 1-oxidoreductase (1.1.1.47)	1243	309	5.1
propanoyl-CoA:phosphate propanoyltransferase (2.3.1.222)	1725	417	5
(S)-2-hydroxyglutarate:quinone oxidoreductase (1.1.5.13)	2190	601	5
4-hydroxyphenylpyruvate:oxygen oxidoreductase (hydroxylating, decarboxylating) (1.13.11.27)	1437	255	5
thiosulfate:ferricytochrome-c oxidoreductase (1.8.2.2)	1361	336	5

This high count is actually reflected in recent literature, although it was with animal models and not humans (in our case).

 Moreover, the fecal metabolomic analysis identified 468 differential expressed metabolites. Among all the differential metabolites, 11 specific pathways significantly altered, which were mainly belonged to lipid and amino acid metabolism.

Comparative analysis of gut microbiota and fecal metabolome features among multiple depressive animal models [2022]

Given the huge numbers of enzymes, I decided to see what came up from KEGG calculations for appropriate probiotics. If you have depression, the site will compute those specific for yourself. As seems to happen often, E.Coli produces a lot of different enzymes and thus at the top of the list.

Tax_Name	Contribution
Escherichia coli	200.9
Bacillus thuringiensis	70.2
Bacillus licheniformis	67
Bacillus subtilis	64.5
Bacillus subtilis subsp. natto	63
Bacillus pumilus	58
Bacillus velezensis	57.8
Bacillus amyloliquefaciens	56.8
Brevibacillus laterosporus	45
Lactobacillus plantarum subsp. plantarum	31.5
Lactiplantibacillus plantarum	31.4
Clostridium beijerinckii	28.3
Lacticaseibacillus rhamnosus	23
Lacticaseibacillus casei	23

Bottom Line

The high number of statistically significant enzymes was a surprise — but checking the literature, it appears to be in agreement with other studies. The special study suggestions engines are available now. Either via the a priori suggestion or the suggestions specific for your microbiome.

Given these facts, fixing depression may be a challenge until someone develops a Shuttleworthia and a Actinobacillus probiotic.

One thing about dealing with the microbiome is the need to constantly check and test your assumptions and revised from the results of tests. The series of A new specialized selection of suggestions links shattered several reasonable assumptions that appears to be false for most people, namely:

• A surplus of specific bacteria is not the cause (no statistical significance was found)
• A surplus of specific enzymes is not the cause (no statistical significance was found)
• Abundance or deficiency of certain compounds rarely has any statistical significance.

What keeps showing up as statistically significant are:

• An insufficient number of “good guy” bacteria — I do NOT mean traditional internet-lore good guy bacteria.
• An insufficient number of specific enzymes being produced.

In every study we have had 99% of the items being statistically significant at the 99% level being deficiency, i.e. with a condition, the mean of those with the condition is less than the mean of the reference group. The 1% that show up as too high are usually at relatively low z-score and is a surprising good match to the number expected from the False Detection Rate. In other words, they were false significant.

This means that some refactoring is planned. The first one is to give an option to get suggestions ONLY from the undergrowth. The second one, revised the probiotic suggestions from using the genomic data from KEGG: Kyoto Encyclopedia of Genes and Genomes to match the pattern. This has just been done.

A common pattern that I have seen in the enzyme data has been that the mean of the study group was about 30% of the mean of the reference group. So, the shotgun approach is to flag in a sample all of the enzymes that are less than 30% of the refence group (using lab specific data). From the flagged enzymes, we look at all of the available probiotics as well as potential probiotics species and see which ones produces the most of the missing enzymes. My expectation is that often the best of these probiotics may “kick ass”, in the case of a ME/CFS person “Just started it and wow does this one give me crazy dreams and headaches. I even tried it in the morning and still the same result.  Did you just power though or any pointers to deal with the herx” 

PLACEHOLDER — VIDEO COMING