Special Studies: General Fatigue

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

SymptomReferenceStudy
General Fatigue1095134
  • 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.

BacteriaReference MeanStudyZ-Score
Lactiplantibacillus pentosus (species)114225.3
Prevotella copri (species)68098218645.2
Gammaproteobacteria (class)1438259445.2
Veillonella (genus)402223245.1
Escherichia coli (species)8291965

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

EnzymeReference MeanStudy MeanZ-Score
[cysteine desulfurase]-S-sulfanyl-L-cysteine:[molybdopterin-synthase sulfur-carrier protein]-Gly-Gly sulfurtransferase (2.8.1.11)540724206
3-(cis-5,6-dihydroxycyclohexa-1,3-dien-1-yl)propanoate:NAD+ oxidoreductase (1.3.1.87)5971445.5
3-phenylpropanoate,NADH:oxygen oxidoreductase (2,3-hydroxylating) (1.14.12.19)6111485.5
deoxyribocyclobutadipyrimidine pyrimidine-lyase (4.1.99.3)431116685.5
tRNA-uridine65 uracil mutase (5.4.99.26)420117335.4
S-adenosyl-L-methionine:23S rRNA (guanine2069-N7)-methyltransferase (2.1.1.264)585030675.3
propanoyl-CoA:oxaloacetate C-propanoyltransferase (thioester-hydrolysing, 1-carboxyethyl-forming) (2.3.3.5)15755015.2
N4-acetylcytidine amidohydrolase (3.5.1.135)308312795.2
ATP:D-tagatose 6-phosphotransferase (2.7.1.101)4151125.1
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate pyruvate-lyase (succinate-forming) (4.1.3.30)15244845.1
acyl-CoA:sn-glycerol-3-phosphate 1-O-acyltransferase (2.3.1.15)338514385.1
S-adenosyl-L-methionine:tRNA (cytidine32/uridine32-2′-O)-methyltransferase (2.1.1.200)343713905.1
2-(glutathione-S-yl)-hydroquinone:glutathione oxidoreductase (1.8.5.7)326310995.1
galactitol-1-phosphate:NAD+ oxidoreductase (1.1.1.251)10422925
acetyl-CoA:[elongator tRNAMet]-cytidine34 N4-acetyltransferase (ATP-hydrolysing) (2.3.1.193)343013875
S-adenosyl-L-methionine:23S rRNA (uracil747-C5)-methyltransferase (2.1.1.189)337913855
ATP phosphohydrolase (ABC-type, thiamine-importing) (7.6.2.15)363714545
[50S ribosomal protein L16]-L-Arg81,2-oxoglutarate:oxygen oxidoreductase (3R-hydroxylating) (1.14.11.47)344814405
7,8-dihydroneopterin 3′-triphosphate diphosphohydrolase (3.6.1.67)371916345
ATP:N-acetyl-D-glucosamine 6-phosphotransferase (2.7.1.59)338313695
Most Significant (all LOW)
EnzymeReference MeanStudy MeanZ-Score
CTP:N,N’-diacetyllegionaminate cytidylyltransferase (2.7.7.82)5956876504-2.9
1-phosphatidyl-1D-myo-inositol:a very-long-chain (2’R)-2′-hydroxy-phytoceramide phosphoinositoltransferase (2.7.1.227)3914450749-2.9
1,5-anhydro-D-mannitol:NADP+ oxidoreductase (1.1.1.292)6501081029-2.9
alginate oligosaccharide 4-deoxy-alpha-L-erythro-hex-4-enopyranuronate-(1->4)-hexananopyranuronate lyase (4.2.2.26)7972599196-2.8
phosphatidylglycerophosphate phosphohydrolase (3.1.3.27)87820105463-2.7
chondroitin-sulfate-ABC endolyase (4.2.2.20)7177388107-2.7
chondroitin-sulfate-ABC exolyase (4.2.2.21)7177388107-2.7
arabinogalactan 4-beta-D-galactanohydrolase (3.2.1.89)107701128121-2.7
cephalosporin-C acetylhydrolase (3.1.1.41)86153104494-2.7
UDP-N-acetyl-alpha-D-glucosamine 4-epimerase (5.1.3.7)83349100761-2.6
N-sulfo-D-glucosamine sulfohydrolase (3.10.1.1)5963473685-2.6
6-alpha-D-glucan 6-glucanohydrolase (3.2.1.11)6403578529-2.6
GDP-alpha-D-mannose:2-O-alpha-D-mannosyl-1-phosphatidyl-1D-myo-inositol 6-alpha-D-mannosyltransferase (configuration-retaining) (2.4.1.346)4374455284-2.6
The enzymes that are in excess.

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

NamesZ-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
Chemical that have low production
NamesZ-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
Chemical that have high production

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)

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)

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”)

Pro forma Suggestions

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