Special Studies: Depression

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

High Anxiety and Anxiety/tension114985
  • 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”.

BacteriaReference MeanStudyZ-Score
Shuttleworthia (genus)273427.8
Actinobacillus (genus)339806.6
Actinobacillus porcinus (species)181486
Haemophilus (genus)15984255.9
Haemophilus parainfluenzae (species)15984245.9
Pasteurellaceae (family)19735345.8
Pasteurellales (order)19735345.8
Pasteurellaceae incertae sedis (norank)143435.8
[Pasteurella] aerogenes-[Pasteurella] mairii-[Actinobacillus] rossii complex (species group)143435.8
Legionellaceae (family)80405.7
Legionella (genus)80405.7
[Actinobacillus] rossii (species)143465.6
Legionellales (order)81435.2
Thiobacillus thiophilus (species)81245.2
Veillonella dispar (species)823595.1
Thiobacillaceae (family)81255
Thiobacillus (genus)80255

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.

EnzymeReference MeanStudy MeanZ-Score
[cysteine desulfurase]-S-sulfanyl-L-cysteine:[molybdopterin-synthase sulfur-carrier protein]-Gly-Gly sulfurtransferase (
tRNA-uridine65 uracil mutase (
deoxyribocyclobutadipyrimidine pyrimidine-lyase (
acyl-CoA:sn-glycerol-3-phosphate 1-O-acyltransferase (
7,8-dihydroneopterin 3′-triphosphate diphosphohydrolase (
(1->4)-alpha-D-galacturonan lyase (
N4-acetylcytidine amidohydrolase (
diacylglycerol-3-phosphate phosphohydrolase (
1,2-diacyl-sn-glycerol 3-phosphate phosphohydrolase (
acetyl-CoA:[elongator tRNAMet]-cytidine34 N4-acetyltransferase (ATP-hydrolysing) (
S-adenosyl-L-methionine:tRNA (cytidine32/uridine32-2′-O)-methyltransferase (
S-adenosyl-L-methionine:23S rRNA (uracil747-C5)-methyltransferase (
protein dithiol:quinone oxidoreductase (disulfide-forming) (
ATP phosphohydrolase (ABC-type, thiamine-importing) (
ATP:(Kdo)-lipid IVA 3-deoxy-alpha-D-manno-oct-2-ulopyranose 4-phosphotransferase (
[50S ribosomal protein L16]-L-Arg81,2-oxoglutarate:oxygen oxidoreductase (3R-hydroxylating) (
D-glucarate hydro-lyase (5-dehydro-4-deoxy-D-glucarate-forming) (
ATP:N-acetyl-D-glucosamine 6-phosphotransferase (
fatty acyl-[acyl-carrier protein]:alpha-Kdo-(2->4)-alpha-Kdo-(2->6)-(acyl)-[lipid IVA] O-acyltransferase (
[RNA] 5′-hydroxy-ribonucleotide-3′-[RNA fragment]-lyase (cyclicizing; [RNA fragment]-3′- nucleoside-2′,3′-cyclophosphate-forming and hydrolysing) (
ATP:N-acyl-D-mannosamine 6-phosphotransferase (
n/a (
coproporphyrinogen:oxygen oxidoreductase (decarboxylating) (
D-amino acid:quinone oxidoreductase (deaminating) (
gamma-L-glutamyl-L-cysteinyl-glycine:spermidine amidase (
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] (
CMP-N-acetyl-beta-neuraminate:beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-R (2->3)-N-acetyl-alpha-neuraminyltransferase (configuration-inverting) (
galactarate hydro-lyase (5-dehydro-4-deoxy-D-glucarate-forming) (
methanesulfonate,FMNH2:oxygen oxidoreductase (
alkanesulfonate,FMNH2:oxygen oxidoreductase (
donor:hydrogen-peroxide oxidoreductase (
D-glucose:ubiquinone oxidoreductase (
glutathione:hydroperoxide oxidoreductase (
3-hydroxybutanoyl-CoA 3-epimerase (
acetyl-CoA:glyoxylate C-acetyltransferase [(S)-malate-forming] (
L-methionine:2-oxo-acid aminotransferase (
S-adenosyl-L-methionine:23S rRNA (guanine2069-N7)-methyltransferase (
ferredoxin:NAD+ oxidoreductase (
choline:acceptor 1-oxidoreductase (
n/a (
isocitrate glyoxylate-lyase (succinate-forming) (
acetyl-CoA:dTDP-4-amino-4,6-dideoxy-alpha-D-galactose N-acetyltransferase (
(S)-3-hydroxyacyl-CoA:NAD+ oxidoreductase (
N-acyl-D-amino acid amidohydrolase (
2-(glutathione-S-yl)-hydroquinone:glutathione oxidoreductase (
S-(hydroxymethyl)glutathione:NAD+ oxidoreductase (
succinyl-CoA:3-oxo-acid CoA-transferase (
n/a (
L-2,4-diaminobutanoate carboxy-lyase (propane-1,3-diamine-forming) (
formate:[oxidized hydrogenase] oxidoreductase (
S-methyl-5-thio-D-ribulose 1-phosphate 1,3-isomerase (
RX:glutathione R-transferase (
n/a (
gamma-L-glutamyl-L-cysteine:glycine ligase (ADP-forming) (
D-glucose:NAD(P)+ 1-oxidoreductase (
propanoyl-CoA:phosphate propanoyltransferase (
(S)-2-hydroxyglutarate:quinone oxidoreductase (
4-hydroxyphenylpyruvate:oxygen oxidoreductase (hydroxylating, decarboxylating) (
thiosulfate:ferricytochrome-c oxidoreductase (

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.

Escherichia coli200.9
Bacillus thuringiensis70.2
Bacillus licheniformis67
Bacillus subtilis64.5
Bacillus subtilis subsp. natto63
Bacillus pumilus58
Bacillus velezensis57.8
Bacillus amyloliquefaciens56.8
Brevibacillus laterosporus45
Lactobacillus plantarum subsp. plantarum31.5
Lactiplantibacillus plantarum31.4
Clostridium beijerinckii28.3
Lacticaseibacillus rhamnosus23
Lacticaseibacillus casei23

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.