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Study M1072

Study name

Teng T 2023

Title

Disturbances of purine and lipid metabolism in the microbiota-gut-brain axis in male adolescent nonhuman primates with depressive-like behaviors

Overall design

The aim of this study was to explore the unique characteristics and pathophysiological mechanisms of adolescent depression from a microbiota-gut-brain axis perspective. Male cynomolgus macaques (Macaca fascicularis) were divided into the following 2 groups (n = 5 in each group): (1) control group, and (2) CUMS group. The CUMS group was exposed to seven days of CUMS stress followed by a four-day behavior observation period; this regimen was conducted for five cycles. The metabolite profiles of microbiota-gut-brain axis including central (prefrontal cortex, hippocampus, and amygdala) and peripheral (plasma, gut and feces of cecum, ascending colon, transverse colon, and descending colon) samples were analyzed by metabolomic profiling.

Study Type

Type1;

Data available

Unavailable

Organism

Non-human primate; Cynomolgus monkey;

Categories of depression

Animal model; Chronic mild stress model; Chronic mild stress model;

Criteria for depression

Behavioral observations

Sample size

10

Tissue

Central; Brain; Prefrontal cortex;

Peripheral; Gut; Intestine;

Peripheral; Faece; Faece;

Central; Brain; Hippocampus;

Central; Brain; Amygdala;

Peripheral; Blood; Plasma;

Platform

MS-based; LC-MS: 1290 Infinity LC (Agilent Technologies) with AB SciexTripleTOF 6600;

PMID

37068733

DOI

10.1016/j.jare.2023.04.010

Citation

Teng T, Clarke G, Wu J, et al. Disturbances of purine and lipid metabolism in the microbiota-gut-brain axis in male adolescent nonhuman primates with depressive-like behaviors. J Adv Res. 2023 Apr 15:S2090-1232(23)00116-9.

Metabolite

Glyceric acid;

myo-Inositol;

Citric acid;

Pyroglutamic acid;

Stearic acid;

3-Hydroxybutyric acid;

Glutaric acid;

N-Acetyl-L-aspartic acid;

L-Glutamic acid;

L-Methionine;

Indole-3-propionic acid;

Homovanillic acid;

Adipic acid;

5-Hydroxyindoleacetic acid;

D-Glucose;

L-Arginine;

Uridine;

Pantothenic acid;

Taurocholic acid;

Cholic acid;

LysoPC(16:0);

Propionylcarnitine;

Phenylacetylglycine;

Indoleacetic acid;

Hydroxyphenyllactic acid;

Hypoxanthine;

Uric acid;

Xanthine;

Taurine;

Creatine;

N-Acetyl-L-glutamic acid;

Indolelactic acid;

Niacinamide;

2-Hydroxybutyric acid;

Docosahexaenoic acid;

Inosine;

Xanthosine;

Citrulline;

Phenylethylamine;

LysoPC(18:0);

Trimethylamine;

CDP-Ethanolamine;

5-Thymidylic acid;

dGTP;

Hydroxyisocaproic acid;

Guanosine monophosphate;

L-Acetylcarnitine;

L-Carnitine;

Adenine;

4-Deoxyerythronic acid;

Malonic acid;

D-Mannose;

Glycocholic acid;

LysoPC(15:0/0:0);

Oleamide;

Putrescine;

Uridine 5'-monophosphate;

4-Pyridoxic acid;

Thymine;

dGDP;

ADP;

Allantoin;

LysoPC(P-16:0);

LysoPC(16:1/0:0);

Deoxycholic acid glycine conjugate;

Octadecanamide;

Palmitic amide;

Deoxycholic acid;

Guanosine;

3-(3-Hydroxyphenyl)propanoic acid;

O-Phosphoethanolamine;

N-acetyltryptophan;

N-Acetylleucine;

Orotic acid;

L-Palmitoylcarnitine;

Alpha-Linolenic acid;

SM(d18:1/18:0);

MG(0:0/16:0/0:0);

(R)-3-hydroxybutyrylcarnitine;

Sphingosine;

Dihydroxyacetone;

gamma-Glutamylglutamic acid;

PE(P-16:0e/0:0);

Deoxycytidine;

LysoPC(20:0/0:0);

3-O-Sulfogalactosylceramide (d18:1/22:0);

Prostaglandin D2;

Palmitoylethanolamide;

Prostaglandin E2;

Uridine diphosphate-N-acetylglucosamine;

Oleoylethanolamide;

LysoPC(18:2(9Z,12Z));

LysoPC(O-18:0);

LysoPC(20:4/0:0);

Sphinganine;

13-HODE;

Uridine diphosphate glucose;

LysoPE(0:0/18:0);

LysoPE(20:2(11Z,14Z)/0:0);

PI(18:0/0:0);

LysoPE(16:0/0:0);

1-heptadecanoyl-sn-glycero-3-Phosphocholine;

FAD;

LysoPC(20:3(8Z,11Z,14Z)/0:0);

LysoPC(20:2(11Z,14Z)/0:0);

PE(20:4(5Z,8Z,11Z,14Z)/P-16:0);

Urocanic acid;

3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid;

2,4,12-Octadecatrienoic acid isobutylamide;

VPGPR Enterostatin;

Isonicotinic acid;

LysoPC(17:0/0:0);

2-Indolecarboxylic acid;

2E,4E,8Z,10E-Dodecatetraenoic acid;

Docosadienoate (22:2n6);

Muramic acid;

D-Glucaric acid;

D-Ornithine;

Galactose 1-phosphate;

5-(2-Hydroxyethyl)-4-methylthiazole;

LysoPC(18:1(9Z));

1-Hexanol;

Sorbitan stearate;

LysoPC(14:0/0:0);

Cyclohexylamine;

Ceanothenic acid;

LysoPI(16:0/0:0);

3'-AMP;

Coprocholic acid;

LysoPE(0:0/22:4(7Z,10Z,13Z,16Z));

PS(20:3(8Z,11Z,14Z)/22:6(4Z,7Z,10Z,13Z,16Z,19Z));

Tetradecanedioic acid;

Hexadecanedioic acid;

N1-Acetylspermidine;

C17 Sphinganine;

N2-Acetylornithine;

Androsterone glucuronide;

N-Acetylcadaverine;

Adenosine diphosphate ribose;

Phenylacetylglutamine;

3-Methoxy-4-Hydroxyphenylglycol sulfate;

Hesperetin;

Guanosine diphosphate;

N-Acetylgalactosamine;

MG(0:0/16:1(9Z)/0:0);

Indole-3-carbinol;

LysoPI(0:0/18:0);

LysoPE(0:0/22:2(13Z,16Z));

PC(18:1(11Z)/20:4(5Z,8Z,11Z,14Z));

LysoPC(P-18:1(9Z));

SM(d18:0/16:1(9Z));

LysoPC(P-18:0/0:0);

LysoPA(18:1(9Z)/0:0);

LysoPA(16:0/0:0);

Ricinoleic acid;

Docosahexaenoyl Ethanolamide;

8-Amino-7-oxononanoic acid;

4-[5]-Ladderane-butanoic acid;

9,10-DHOME;

Xestoaminol C;

2(R)-hydroxydocosanoic acid;

Daidzein;

13-Tetradecen-2,4-diyn-1-ol;

1-(11Z-eicosenoyl)-glycero-3-phosphate;

1,3-Dihydro-(2H)-indol-2-one;

Glycitein;

Ethyl (±)-3-hydroxybutyrate;

Phosphoadenosine phosphosulfate;

Acetylvalerenolic acid;

Adenosine 3',5'-diphosphate;

Allocystathionine;

Arginylglutamic acid;

Histidylproline;

9-OxoODE;

2-Ethyl-2-Hydroxybutyric acid;

Prostaglandin F3a;

Ceanothine E;

PE(16:0/18:2(9Z,12Z));

N-Acetylmannosamine;

3-Hydroxypristanic acid;

LysoPE(18:2(9Z,12Z)/0:0);

Ciclesonide;

LysoPI(18:1(9Z)/0:0);

LysoPG(16:0/0:0);

LysoPC(18:1(11Z)/0:0);

Glutamylmethionine;

9,10,13-TriHOME;

CPA(18:1(11Z)/0:0);

Valylproline;

Linoleoyl ethanolamide;

Genistein;

9,10-Epoxystearic acid;

LysoPE(0:0/20:1(11Z));

Lathosterol;

Ammonia;

Ursodeoxycholic acid;

21-Deoxycortisol;

LysoPC(18:3(9Z,12Z,15Z)/0:0);

(9S,10S)-9,10-dihydroxyoctadecanoate;

3-Hydroxytetradecanedioic acid;

5'-Deoxyadenosine;

12S-hydroxy-5E,8Z,10Z,14Z-eicosatetraenoic acid;

Dodecanedioic acid;

PE(18:1(9Z)/0:0);

Tauroursodeoxycholic acid;

Tetracosahexaenoic acid;

PC(16:0/0:0);

9-Oxo-nonanoic acid;

2-Methyl-3-phenyl-2-propenal;

1-(Hydroxymethyl)-5,5-dimethyl-2,4-imidazolidinedione;

Phytolaccoside I;

MG(15:0/0:0/0:0);

5-Methylfuran-2-carboxylic acid;

trans-p-Menthane-1,7,8-triol 8-glucoside;

Hydroxybutyrylglycine;

Ethyl hydrogen sulfate;

Thiomorpholine 3-carboxylate;

Equol;

1-Isothiocyanato-7-(methylthio)heptane;

2-Hydroxy-2-(2-oxopropyl)butanedioic acid;

N-Oleoyl-L-Serine;

Laccaic acid D;

6-methoxy-3-(4-methoxyphenyl)-3,4-dihydro-2H-1-benzopyran-7-ol;

17beta-hydroxy-5beta-estran-3-one;

6-Hydroxyhexanoic acid;

(E)-2-Octen-1-ol;

L-alpha-Amino-1H-pyrrole-1-hexanoic acid;

(3R)-3,4-Dihydroxy-3-(hydroxymethyl)butanenitrile 4-glucoside;

2,4-octadienoylglycine;

Galactosyl 4-hydroxyproline;

3alpha-Hydroxyoreadone;

Isopropylbenzene;

6-Methylquinoline;

3-Hydroxy-2-oxoindole;

Alpha-Hydroxymidazolam;

Stercobilin;

2beta,9xi-Dihydroxy-8-oxo-1(10),4,11(13)-germacratrien-12,6alpha-olide;

12-Ketodeoxycholic acid;

xi-7-Hydroxyhexadecanedioic acid;

Alanylhydroxyproline;

Lumichrome;

3-Phenylpropyl acetate;

13-HOTE;

PS(18:1(9Z)/0:0);

MG(0:0/14:1(9Z)/0:0);

4-Hydroxyproline galactoside;

11-Hydroxy-9-tridecenoic acid;

8-Acetylegelolide;

PE(14:0/14:0);

2-Hydroxyglutaric acid lactone;

Enterolactone;

3beta-Hydroxychola-5,7-dien-24-oic Acid;

3,7,8,15-Scirpenetetrol;

gamma-Glutamyl-S-methylcysteine;

N-Acetylhistamine;

7alpha-hydroxy-3-oxochol-4-en-24-oic Acid;

N-Arachidonoyl tyrosine;

2-Formaminobenzoylacetate;

2-Oxo-1,2-dihydroquinoline-4-carboxylate;

2-Hydroxy-2,6,6-trimethylcyclohexanone;

3alpha,7alpha-Dihydroxycoprostanic acid;

9,12-Octadecadiynoic acid;

1-nonadecanoyl-glycero-3-phosphate;

13(S)-HODE methyl ester;

4,11,13,15-Tetrahydroridentin B;

LysoPE(15:0/0:0);

(3beta,5alpha,6alpha,7alpha,22E,24R)-5,6-Epoxyergosta-8,14,22-triene-3,7-diol;

N-Acetyl-L-tyrosine;

7,10-Hexadecadiynoic acid;

N1,N12-Diacetylspermine;

3,11,12-Trihydroxy-1(10)-spirovetiven-2-one;

3,4-Dihydroxy-2-hydroxymethyl-1-pyrrolidinepropanamide;

alpha-Methylphenylalanine;

Isoquinoline;

Antibiotic X 14889A;

Drostanolone;

Rishitin;

3,3-Dimethylglutaric acid;

Glyuranolide;

N5-(4-Methoxybenzyl)glutamine;

4-Methylbenzaldehyde;

LysoPE(14:0/0:0);

PE(14:0/0:0);

Pantothenamide;

Corchorifatty acid A;

12,20-DiHETE;

1-Hydroxy-3-nonanone;

2-(2-Aminoethyl)indole;

Trans-EKODE-(E)-Ib;

(S)-9-Hydroxy-10-undecenoic acid;

(S)-Piperidine-2-carboxamide;

Polysorbate 20;

(3beta,17alpha,23S)-17,23-Epoxy-3,29-dihydroxy-27-norlanost-8-en-24-one;

(23S,24S)-17,23-Epoxy-24,29-dihydroxy-27-norlanost-8-ene-3,15-dione;

Pubesenolide;

N,N-dimethyl-Safingol;

Ganoderic acid G;

Bisnorcholic acid;

Ananasic acid;

Polyporusterone E;

(17alpha,23S)-Epoxy-28,29-dihydroxy-27-norlanost-8-ene-3,24-dione;

Camelliagenin C;

Arachidoyl Ethanolamide;

3,4-Dihydrocadalene;

Atracurium;

Palmitoleamide;

5-Hydroxy-7-eicosanone;

Glabric acid;

Agavasaponin C;

Camellenodiol;

PE(15:0/14:0);

PE(14:0/P-16:0);

Isolinderanolide;

7-Ketodeoxycholic acid;

Perillyl alcohol;

N-(1-Deoxy-1-fructosyl)proline;

Goshuyic acid;

Deuteroporphyrin IX;

9Z,13-Tetradecadien-11-ynal;

Cis-Quinceoxepane;

9,12,15-Octadecatrien-1-ol;

Crucigasterin 277;

PE(16:0/15:0);

Tetracosahexaenoic acid, n-3;

PE(18:0/18:2(9Z,12Z));

5-Isopropyl-2-(2-methylpropyl)-2-cyclohexen-1-one;

Cer(t18:0/16:0);

DG(22:4n6/0:0/22:5n3);

PE(15:0/18:2(9Z,12Z));

Medicagenic acid;

16beta-16-Hydroxy-3-oxo-1,12-oleanadien-28-oic acid;

Fumonisin B1;

Cer(d18:0/18:0(2OH));

SM(d18:0/16:0);

L-Histidine trimethylbetaine;

15-Keto-13,14-dihydroprostaglandin A2;

S-Allylcysteine;

Ercalcitriol;

PE(P-18:1(11Z)/18:3(6Z,9Z,12Z));

11'-Carboxy-gamma-chromanol;

2,3,6-Trimethylbenzaldehyde;

(3beta,17alpha,23R)-17,23-Epoxy-3,29-dihydroxy-27-norlanost-8-ene-15,24-dione;

3-O-cis-Coumaroylmaslinic acid;

PE(P-18:1(11Z)/14:0);

Tanacetol B;

Cer(d14:1(4E)/20:0(2OH));

PE-NMe(18:0/20:2(11Z,14Z));

Dihydroferuperine;

Yuzu lactone;

R1128B;

TG(18:1(11Z)/20:3(5Z,8Z,11Z)/20:5(5Z,8Z,11Z,14Z,17Z));

TG(18:1(11Z)/20:3(5Z,8Z,11Z)/22:6(4Z,7Z,10Z,13Z,16Z,19Z));

Ganoderic acid L;

4-Methylthiazole;

PI-Cer(d20:0/16:0(2OH));

Topaquinone;

Norophthalmic acid;

(2R,3R,4R)-2-Amino-4-hydroxy-3-methylpentanoic acid;

PI(16:0/20:4(8Z,11Z,14Z,17Z));

L-a-Lysophosphatidylserine;

C16 Sphingosine;

3-O-Caffeoyl-1-O-methylquinic acid;

Dimethadione;

Cascaroside C;

4-Hydroxy-2-oxoglutaric acid;

Maltotetraose;

LysoPE(0:0/22:0);

1,4-beta-D-Glucan;

Goshonoside F5;

D-4'-Phosphopantothenate;

Pectic acid;

Aquifoliunine EII;

3alpha-Hydroxy-5beta-chola-7,9(11)-dien-24-oic Acid;

Soyasaponin III;

2-Acetyl-1,5,6,7-tetrahydro-6-hydroxy-7-(hydroxymethyl)-4H-azepine-4-one;

Chenodeoxycholic acid sulfate;

2-Methylguanosine;

Gamma-L-Glutamyl-L-pipecolic acid;

Ginsenoyne A linoleate;

15(S)-Hydroxyeicosatrienoic acid;

D-Urobilinogen;

Glycinol;

3,4,5-trihydroxy-6-(3-phenylpropoxy)oxane-2-carboxylic acid;

Cortolone;

(2xi,4xi)-4,4',5,7-Tetrahydroxyflavan;

N2,N2-Dimethylguanosine;

13,14-Dihydro-15-keto-PGE1;

N,N-Didesmethyltramadol;

Methyl-10-hydroperoxy-8E,12Z,15Z-octadecatrienoate;

Di-4-coumaroylputrescine;

Demethoxyshogaol;

LysoPA(O-18:0/0:0);

Mupirocin;

22-Angeloylbarringtogenol C;

9(S)-HOTrE;

6-[5]-ladderane-hexanoic acid;

Kinetensin 1-3;

3-Methyl-5-pentyl-2-furannonanoic acid;

Neuromedin N (1-4);

Styrene;

Punicic acid;

10-Hydroxy-octadec-12Z-enoate-9-beta-D-glucuronide;

Polyethylene, oxidized;

Dihydrodaidzein;

Tyrosyl-Isoleucine;

Methyl linolenate;

(10E,12Z)-(9S)-9-Hydroperoxyoctadeca-10,12-dienoic acid;

Pisumsaponin II;

Neuraminic acid;

Cavipetin A;

1-Stearoylglycerophosphoglycerol;

13(S)-Hydroperoxylinolenic acid;

12-oxo-PDA;

6-Hydroxynicotinic acid;

Soyasaponin II;

PC(19:0/0:0);

(4E,8E,10E-d18:3)sphingosine;

Secasterone;

1,4,5-Naphthalenetriol;

(±)-(Z)-2-(5-Tetradecenyl)cyclobutanone;

Pelargonidin;

Frangulanine;

Pokeberrygenin;

Sterebin E;

Lucyin A;

Mangiferic acid;

Methyl ricinoleate;

Rockogenin;

Glabranin;

Soyasaponin I;

Soyasaponin IV;

Cucurbitacin B;

Gingerglycolipid A;

Cucurbic acid;

CPA(18:2(9Z,12Z)/0:0);

Alfacalcidol;

7C-aglycone;

Dibutyl malate;

Lucidone B;

PC(14:0/0:0);

Lysylproline ;

Quinaprilat;

Diosmetin;

4-(4-Methyl-3-pentenyl)-3-cyclohexene-1-carboxaldehyde;

p-Mentha-1,3,5,8-tetraene;

DG(15:0/20:4(8Z,11Z,14Z,17Z)/0:0);

sn-glycero-3-Phosphoethanolamine;

Dehydrocyanaropicrin;

cis-3-Hexenyl trans-2-hexenoate;

7-Methylguanosine 5'-phosphate;

Farrerol;

2-n-Propyl-4-oxopentanoic acid;

2-Linoleoyl Glycerol;

4-Methyl-1-phenyl-2-pentanol;

Presqualene diphosphate;

6-[2-(2H-1,3-benzodioxol-5-yl)ethyl]-4-hydroxy-5,6-dihydro-2H-pyran-2-one;

Tetrahydro-2-furanmethanol;

8-Hydroxy-5,6-octadienoic acid;

Benzofuran;

Calamusenone;

Ganoderenic acid C;

10-Hydroxymelleolide;

Cytochalasin Ppho;

PE(16:0/0:0);

2-Piperidinone;

(24S)-24,25-dihydroxyvitamin D3;

N2,N5-Dibenzoyl-L-ornithine;

8,11-eicosadiynoic acid;

4'-O-methyl-(-)-epicatechin-5-O-beta-glucuronide;

Methyl (3b,11x)-3-Hydroxy-8-oxo-6-eremophilen-12-oate;

Lithocholate 3-O-glucuronide;

N1,N10-Dicoumaroylspermidine;

cis-Uvariamicin IB;

6-[5]-ladderane-1-hexanol;

6-hydroxysphingosine;

Polyoxyethylene (600) monoricinoleate;

Malvidin;

Gamma-Glutamylvaline;

PC(17:1(9Z)/0:0);

Coumarin;

Soyasapogenol C;

1-Oleoylglycerophosphoserine;

PE(O-16:0/0:0);

[3-(3,7-dihydroxy-3,4-dihydro-2H-1-benzopyran-2-yl)phenyl]oxidanesulfonic acid;

12-Oxo-20-trihydroxy-leukotriene B4;

Estrane-3alpha,17alpha-diol;

1-Hydroxyepiacorone;

Goshonoside F2;

Beta-Cortolone;

Cis-12-Octadecenoic Acid methyl ester;

MG(19:0/0:0/0:0);

N-Stearoyl Proline;

6,8,10,12-pentadecatetraenal;

PS(O-16:0/0:0);