Figure 5

The MSTM networks (229 nodes and 1,044 edges). Yellow circle: gut microbiota; pink circle: signaling pathway; orange circle: target; violet circle: metabolite. (A) Microbiota. Firmicutes: FM; Fusobacteria: FB; Escherichia coli; E.coli; Lactobacillus acidophilus ATCC 4357: LA; Lactobacillus rhamnosus GG: LRGG; Lactobacillus: LB; Dictyostelium discoideum: DD; Enterococcus durans M4-5: ED; Lactobacillus paracasei JS1: LPJS1; Faecalibacterium prausnitzii A2-165: FPA; Eubacterium limosum: EL; Enterococcus durans EP1: EDEP1; Enterococcus durans EP2: EDEP2; Enterococcus durans EP3: EDEP3; Lachnospiraceae: LS; Streptococcus salivarius JIM8772: SSJ; Faecalibacterium prausnitzii L2-6: FPL; Faecalibacterium prausnitzii M 21/2: FPM; Faecalibacterium prausnitzii CNCM I-4541: FPI4541; Faecalibacterium prausnitzii CNCM I-4543: FPI4543, Faecalibacterium prausnitzii CNCM I-4546: FPI4546; Faecalibacterium prausnitzii CNCM I-4573: FPI4573; Faecalibacterium prausnitzii CNCM I-4644: FPI4644; Faecalibacterium prausnitzii CNCM I-4575: FPI4575; Bifidobacterium adolescentis: BA; Bacteroides vulgatus: BV; Bacteroides distasonis: BD; Streptococcus salivarius: SS; Faecalibacterium prausnitzii: FP; Lactobacillus plantarum L9: LPL9; Bacteroides fragilis ATCC 23,745: BF; Streptococcus salivarius CIP102503: SSC; Akkermansia muciniphila ATCC BAA-835: AMBA; Faecalibacterium prausnitzii A2 < U + 2013 > 165: FPA2; Akkermansia muciniphila: AM; Eubacterium: EB; Enterococcus: EC; Bifidobacterium: BFB; Bacteroides: BI; Salmonella enterica: SE; Clostridium butyricum ATCC 19,398: CB. (B) Signaling pathways. hsa04620: Toll-like receptor signaling pathway; hsa04657: IL-17 signaling pathway; hsa04933: AGE-RAGE signaling pathway in diabetic complications; hsa04668: TNF signaling pathway; hsa04917: Prolactin signaling pathway; hsa04660: T cell receptor signa;ing pathway; hsa05120: Epithelial cell signaling in Helicobacter pylori infection; hsa04722: Neurotrophin signaling pathway; hsa04662: B cell receptor signaling pathway; hsa04370: VEGF signaling pathway; hsa04071: Sphingolipid signaling pathway; hsa04068: FoxO signaling pathway; hsa04919: Thyroid hormone signaling pathway; hsa04064: NF-kappa B signaling pathway; hsa04920: Adipocytokine signaling pathway; hsa04062: Chemokine signaling pathway; hsa04630: JAK-STAT signaling pathway; hsa04926: Relaxin signaling pathway; hsa04622: RIG-I-like receptor signaling pathway; hsa04621: NOD-like receptor signaling pathway; hsa04915: Estrogen signaling pathway; hsa04024: cAMP signaling pathway; hsa04910: Insulin signaling pathway; hsa04072: Phospholipase D signaling pathway; hsa04150: mTOR signaling pathway; hsa04912: GnRH signaling pathway; hsa04151: PI3K-Akt signaling pathway; hsa04010: MAPK signaling pathway; hsa04921: Oxytocin signaling pathway; hsa04371: Apelin signaling pathway; hsa04014: Ras signaling pathway; hsa04022: cGMP-PKG signaling pathway; hsa04261: Adrenergic signaling in cardiomyocytes; hsa04015: Rap1 signaling pathway; hsa04310: Wnt signaling pathway; hsa04550: Signaling pathways regulating pluripotency of stem cells; hsa04330: Notch signaling pathway. (C) Targets. HDAC5: Histone deacetylase 5; ADRA2B: Alpha-2B adrenergic receptor; HCAR2: Hydroxycarboxylic acid receptor 2; ADRB2: Adrenoceptor Beta 2; HDAC3: Histone Deacetylase 3; HDAC2: Histone Deacetylase 2; HDAC1: Histone Deacetylase 1; CTSD: Cathepsin D; IL2: Interleukin 2; TLR4: Toll-like receptor 4; TLR9: Toll-like receptor 9; AKT1: AKT Serine/Threonine Kinase 1; EGFR: Epidermal Growth Factor Receptor; CXCL8: C-X-C Motif Chemokine Ligand 8; PTGS2: Prostaglandin-Endoperoxide Synthase 2; MAPK8: Mitogen-Activated Protein Kinase 8; IL6: Interleukin-6; JUN: Jun Proto-Oncogene, AP-1 Transcription Factor Subunit; GSK3B: Glycogen synthase kinase-3 beta; RELA: RELA Proto-Oncogene, NF-KB Subunit; MAPK14: Mitogen-Activated Protein Kinase 14; CASP3: Caspase 3; MAPK1: Mitogen-Activated Protein Kinase 1. (D) Metabolites. Phenylacetylglutamine: PAG; Naringenin chalcone: NC; Caffeic acid: CA; Phenylacetic acid: PA; Equol: EQ; Dihydroisoferulic acid: DA; 1,3-Diphenylpropan-2-ol: 1,3-D-2; Enterodiol: ETD; 3-Phenylpropionic acid: 3-PA; Pioglitazone: PGZ; Lunularin: LL; 3-Indolepropionic acid: 3-IA; Tretinoin: TN; Phloretin: PR; Icaritin: IR; Secoisolariciresinol: SLS; Apigenin: AG; Luteolin: LTL; Diosmetin: DS; Kaempferol: KP; Genistein: GS; Demethyltexasin: DMT; Quercimeritrin: QCM; Phenylalanine: PLA; Indole-3-lactic acid: I-3-LA; 11-Methoxycurvularin: 11-M; Dihydroresveratrol: DHR; Ethyl phenyllactate, (-)-: EP; Stilbene-3,4-diol: S-3,4-D; (S,R)-1-O-caffeoylglycerol: 1-O-C; Daidzein: DZ; Quercetin: QR; Acacetin: AC; Chrysin: CS; Urolithin A: UA; Indole-3-carboxylic acid: I-3-C; 3,4-Dihydroxyphenylacetic acid: 3,4-DA; Isoquercitrin: IQ; 10-Keto-12Z-octadecenoic acid: 10-K-12-O; Compound K: CK; 3-Methyloxindole: 3M; Oxindole: OI; (20S)-Protopanaxadiol: 20SP; Protopanaxadiol: PPD; Diosgenin: DG; Baohuoside I: BAI; Myricetin: MC; Baicalein: BAC; CHEBI:137478: C13; Levodopa: LD; Butyrate: BT; 10-Oxo-11-octadecenoic acid: 10-O-11-O; Baicalin: BC; Phloretic acid: PHA; HPLA: HP; Glycitein: GC; Dopamine: DP; Iuro-a: IA; Indole-3-acrylic acid: I-3-A; Dihydroglycitein: DHG; Leucocianidol: LCA; Ponciretin: PC; Danshensuan A: DANA; Hesperetin dihydrochalcone: HD; Platycodin D: PD; Didemethylmatairesinol: DMM; D-Mannose: DM; Acetic: AT; Genipin: GN; (+)-p-Hydroxyhydratropic acid: (+)-p–H; 5-HIAA: 5-HI; 4-Hydroxyphenylacetic acid: 4-HA; Hydroxyquercitrin: HQ; Quercitrin: QC; Acifran: AF; PhlP: PH; Dihydrocaffeic acid: DHDA; AI3-32,395: AI3; luro-a: IA; Serotonin: ST; Glycocholic acid: GCA; Lacto-N-tetraose: LNT; Nicotinic acid: NA; Colibactin: CBC; Palmitic acid: PAA; 8-Prenylnaringenin: 8P; 5-OH-Equol: 5OE; Dihydrogenistein: DHG; Dihydrodaidzein: DHDD; Arctigenin: ATG; Naringenin: NRG; DIF-3: D3; Q51617483: Q5; 3-Hydroxy-4-methoxybenzenepropanoic acid: 3H4A; 5-(Hydroxy-3-indolyl)lactic acid: 5HL; p-Cresol sulfate: p-Cs; Norathyriol: NTR; Phloroglucinol: PRG; Hydroumbellic acid: HDQ; CHEBI:10980: C10; Hydroquinone: HDQ; 5-hydroxyindole-3-lactic acid: 5H3L; 6′-OH-O-Dma: 6OOD; O-Desmethylangolensin: OD; 10-oxo-12Z-octadecenoic acid: 12O; Lithocholic acid: LIA; Ursodeoxycholic acid: URA; Deoxycholic acid: DEA; p-Cresol glucuronide: PCG; Ginsenoside-Rd: GRD; Ginsenoside Rh2: GRH; 20(R)-Ginsenoside Rh2: 20GR; LNnT: LN; Folic acid: FA; 5-(3,4-Dihydroxyphenyl)-valerolactone: 5V; Acetoin: ATI; (R)-3-Hydroxybutyrate: R3H; (S)-3-Hydroxybutyric acid: S3HA; Isovaleric acid: ISVA; Isobutyric acid: ISBA; Succinate: SC; Valerate: VL; 4-Hydroxybenzoic acid: 4HBA; 3-Hydroxybenzoic acid: 3HBA; 2-Acetoxypropanoic acid: 2APA; D-Glucuronic Acid: DGA.