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”)