Table 1.
Summary of Recent Publications Related to Metabolomics, Gut Microbiome and Xenobiotic Exposure
| Xenobiotics, dose |
(Animal strain) Sample type for metabolomics |
Sample preparation (extraction solvent; ISs; derivatization reagent for GC) |
Column for analytical platform |
Nontargeted metabolomics | Targeted metabolomics | Transcriptomics | Genomics | References | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Analytical platform |
Listed differential metabolites |
Analytical platform |
Target analytes |
|||||||
| BDE-3, 0.0015-30 (mg/kg) | (C57BL/6J) Mouse testis, urine, serum | 80% MeOH (testis), MeOH (urine, serum); 2-Chloro-L-phenylalanine | XSelect HSS T3 | UPLC-Q-TOF/MS | 76, 38, and 31 metabolites in testis, urine, and serum | - | - | - | - | Wei et al. (2018) [128] |
| BDE-47, 10.0 (mg/kg) | (SD) Rat serum | MeOH; N/A; BSTFA | HP-5MS | GC-MS | 26 metabolites | - | - | - | Fecal 16S rRNA Seq | Gao et al. (2021) [129] |
| 18 PBDE congeners, N/A | Human placenta | 80% MeOH; tridecanoate and 3 deuterated ISs; MSTFA | DB-5MS | GC-MS | 66 metabolites | - | - | - | - | Wang et al. (2022) [130] |
| BDE-47, 48.5; BDE-99, 56.5 (mg/kg) | (C57BL/6J) Mouse serum, liver, small and large intestine content | MeOH (serum), ACN-MeOH (liver, small and large intestine content); 5 deuterated ISs | XSelect HSS T3 | - | - | UPLC-QQQ-MS | 56 BAs | Liver RNA-Seq | Fecal 16S rRNA Seq | Li et al. (2018) [86] |
| BDE-47, 48.5; BDE-99, 56.5 (mg/kg) | (C57BL/6J) Mouse serum, liver, small and large intestine content | MeOH (serum), 80% MeOH (liver, small intestine content, large intestine content); 2 13C-labeled ISs | Xbridge BEH Amide | - | - | UPLC-QQQ-MS | >300 aqueous metabolites | Liver RNA-Seq | Fecal 16S rRNA Seq | Scoville et al. (2019) [87] |
| BDE-47, 0.2; TBBPA, 0.2; BPS, 0.2 (mg/kg) | (CD-1) Mouse liver, fecal; fecal (SCFAs) | BAs: ACN-MeOH; 5 deuterated ISs SCFAs: MeOH-H2O; hexanoic acid-6,6,6-d3; MTBSTFA | ZORBAX Eclipse Plus C18; HP-5MS | - | - | UPLC-QQQ-MS; GC-MS | 56 BAs, 14 SCFAs | BA-processing related genes and cytokines in liver | Fecal 16S rRNA Seq | Gomez et al. (2021) [135] |
| PCB 126, 1.0 (μmol/kg) | (Ldlr −/−) Mouse liver; fecal (SCFAs) | SCFAs: MTBE; N/A; MTBSTFA | ACQUITY UPLC BEH C18, UPLC BEH Amide | - | - | UPLC-Q-Exactive; GC-MS | 25 Hepatic Metabolism metabolites; 5 SCFAs | Inflammatory, metabolic, and gut health markers in jejunum and colon | Fecal 16S rRNA Seq | Petriello et al. (2018) [134] |
| Fox River PCB mixture, 6-30 (mg/kg) | (C57BL/6J) Mouse liver, serum | MeOH (serum), 80% MeOH (liver); 2 13C-labeled ISs | XBridge BEH Amide | - | - | UPLC-QQQ-MS | >300 aqueous metabolites | Liver RNA-Seq | Fecal 16S rRNA Seq | Lim et al. (2020) [182] |
| PCB 126, 1.0 (μg/L) | (D.rerio) Zebrafish intestine, serum | 50% ACN (Metabolomics) MeOH and MTBE (lipidomics) ; N/A | ACQUITY UPLC BEH Amide, ACQUITY UPLC HSS T3 | UPLC-Q-Exactive (metabolomics, lipidomics) | - | - | - | BA metabolism related genes in liver | Fecal Metagenomic Seq | Hu et al. (2021) [137] |
| Aroclor 1260 PCB mixture, 20 (ng/kg) | Pig serum | MeOH-H2O-chloroform; 4 deuterated ISs for metabolomics, LPC (15:0), PC (15:0/15:0), and TG (17:0/17:0/17:0 for lipidomics | Hypersil Gold C18, ACQUITY CSH C18 | UPLC-Q-Exactive (metabolomics, lipidomics) | 33 polar metabolites, 39 lipids | - | - | - | - | Hernandez-Mesa et al. (2022) [131] |
| PCB 126, 24 (μg/kg) | (C57BL/6J) Mouse urine, cecal content, liver, fecal | Metabolomics: 80% MeOH BAs: MeOH; deuterated ISs | XSelect HSS T3 (metabolomics); ACQUITY C8 BEH (BAs quantification) | 1H NMR, UPLC-Q-Exactive (metabolomics, lipidomics) | - | UPLC-QQQ-MS | BAs | BA and FA metabolism related genes in liver and intestine | Cecal content 16S rRNA Seq, Cecal content metagenomic Seq | Tian et al. (2022) [230] |
| PCB 126, PCB 153, TCDF, 0.6-6 (μM); TCDD, 0.06-6 (μM) | (C57BL/6J) Mouse cecal microbiota (In vitro) | MeOH-H2O-chloroform; chlorpropamide and 15:0-18:1-d7-PC | Hydro-RP C18, CSH C18 column | 1H NMR, UPLC-Q-Exactive (metabolomics, lipidomics) | - | - | - | Cecal bacterial mixtures RNA-Seq | Cecal bacterial mixtures 16S rRNA Seq | Tian et al. (2020) [231] |
| PFOS, 0.3-30 (μg/g) | (C57BL/6J) Mouse fecal | Diethyl ether; N/A | Rtx-Wax | - | - | GC-MS | 5 SCFAs | Inflammation related genes in colon | Fecal 16S rRNA Seq | Wang et al. (2020) [240] |
| PFOS, 0.003-0.012% for mouse 5-50 (μg/g) for bacterial | (C57BL/6J) Mouse liver, cecal bacterial suspension | FAs: MeOH-chloroform; C15:0 free FA, methyl ester of C17:0 | HP-5MS | 1H NMR | - | GC-MS | 5 FAs | Inflammation and other metabolism related genes in liver | Cecal content 16S rRNA Seq | Zhang et al. (2020) [132] |
| PFOA, 2.5-30 (mg/kg) | (C57BL/6J) Mouse fecal | Diethyl ether; N/A | N/A | - | - | GC-MS | 5 SCFAs | - | Cecal content 16S rRNA Seq | Wang et al. (2021) [241] |
| PFOA, 0.5-3 (mg/kg) | (C57BL/6J) Mouse fecal | Ether; N/A | N/A | - | - | GC-MS | 6 SCFAs | Inflammation related genes in colon | Fecal 16S rRNA Seq | Shi et al. (2020) [242] |
| PFOA, 300 (mg/kg) | (C57BL/6J) Mouse fecal | Ether; N/A | Rtx-Wax | - | - | GC-MS | SCFAs | - | Fecal 16S rRNA Seq | Shi et al. (2021) [243] |
| PFAS, 32.7±1.1 (μg/L) | (Emydura macquarii macquarii) Turtle fecal | N/A; 2 13C labeled ISs | ZORBAX Extend C18 for targeted analysis | UPLC-Q-TOF/MS | - | UPLC-QQQ-MS | Central carbon metabolism metabolites | - | Fecal 16S rRNA Seq | Beale et al. (2022) [244] |
| As, 0.5-10 (ppm) | (SD) Rat serum | MeOH; N/A | Kinetex C18 | UPLC-Orbitrap | 18 metabolites in lipid, amino acid, and nucleotide metabolism | - | - | Lipids and AA metabolism related genes in liver | - | Wang et al. (2015) [259] |
| As, N/A | Human urine | Water (no extraction); N/A | ACQUITY UPLC HSS T3 | UPLC-Q-Exactive | 38 metabolites | - | - | - | - | Khanam et al. (2022) [260] |
| As, 10 (ppm) | (C57BL/6J) Mouse fecal, urine, plasma | MeOH (urine, plasma), 50% MeOH (fecal) ; N/A | Waters C18 T3 | UPLC-Q-TOF/MS | 370 features in fecal, 40 and 10 metabolites in urine and plasma | - | - | - | Fecal 16S rRNA Seq | Lu et al. (2014) [261] |
| As, 10 (ppm) | (C57BL/6J) Mouse serum | MeOH; N/A | Poroshell 120 EC-C18 | UPLC-Q-TOF/MS | 33 metabolites | - | - | - | - | Xue et al. (2019) [262] |
| As, 30 (mg/kg) | (C57BL/6J) Mouse brain | Metabolomics: MeOH-ACN-H2O Lipidomics: MeOH and MTBE; 3 deuterated ISs | ACQUITY UPLC HSS T3, Kinetex C18 | UPLC-Q-TOF-MS/MS (metabolomics), UPLC-Q-Exactive (lipidomics) | 118 polar metabolites, 17 lipids | - | - | - | Fecal 16S rRNA Seq | Wang et al. (2021) [263] |
| As, 30 (mg/kg) | (C57BL/6J) Mouse fecal, plasma, cortex | MeOH-ACN-H2O (fecal, brain); MTBE (plasma) ; N/A | N/A | UPLC-Q-Exactive | 31, 1, and 17 metabolites in fecal, cortex, and plasma | - | - | - | Fecal 16S rRNA Seq | Luo et al. (2023) [133] |
| Cd, 1-5 (μmol/L) | Human urine, Pancreatic beta cells (In vitro) | Urine: No extraction, L-2-chlorophenylalanine Cells: MeOH-ACN | HILIC column | UPLC-TOF/MS | 76 metabolites in cells, 53 metabolites in human urine | - | - | Mitochondrial TCA cycle and fatty acid oxidation related genes in pancreatic beta cells and mouse pancreas | - | Hong et al. (2022) [266] |
| Cd, 1-50 (ppm) | (C57BL/6J) Mouse brain | MeOH-H2O; 13C3-lactate | ACQUITY UPLC BEH C18 | UPLC-Q-Exactive | 101 altered metabolites | UPLC-Orbitrap ID-X | Lactate | Brain RNA-Seq | - | Hudson et al. (2021) [267] |
| Cd 0.6-3 (mg/L) | (Humanized ApoE3-KI and ApoE4-K1) Mouse plasma | MeOH-H20; hexanoic acid-6,6,6-d3; MTBSTFA | HP-5MS | - | - | GC-MS | SCFAs | Liver RNA-Seq and inflammation related genes in liver | Large intestinal content 16S rRNA Seq | Zhang et al. (2021) [268] |
| Cd, As, 50 (ppm) | (C57BL/6J) Mouse fecal | ACN-H2O; N/A | self-packed 15 cm C18 column | UPLC-Q-Exactive | 33 and 2 features in Cd and As treated group | - | - | - | Fecal 16S rRNA Seq | Li et al. (2019) [269] |
| Cd, 0.24-0.46; Se, 0.6-6 (mg/L) | Honey bee abdomen | MeOH-ACN-H2O-isopropanol; N/A | CSH phenyl-hexyl column | UPLC-Q-TOF/MS | 2 Cd-induced and 7 Se-induced metabolites | - | - | - | Whole-bee 16S rRNA Seq | Rothman et al. (2019) [270] |
| Mn, 20 (mg/kg) | (C57BL/6J) Mouse fecal | MeOH-H2O-chloroform; N/A; BSTFA | N/A | GC-MS | 36 and 32 metabolites in female and male mice | - | - | - | Fecal 16S rRNA Seq, Fecal metagenomic Seq | Chi et al. (2017) [275] |
| Mn, 200 (mg/L) | (SD) Rat plasma | MeOH-ACN; N/A | ACQUITY UPLC HSS T3 | UPLC-Q-TOF/MS | 17 metabolites | - | - | - | Fecal 16S rRNA Seq, Fecal metagenomics Seq | Wang et al. (2020) [276] |
| Pb, N/A | Human fecal | MeOH-H2O-chloroform; 11 ISs; BSTFA | HP-5MS | GC-MS | 19 metabolites | - | - | - | Fecal 16S rRNA Seq | Zeng et al. (2022) [277] |
| PM2.5, 198.52 ± 21.56 (μg/m3) | (Balb/C) Mouse ileum | MeOH-H2O-chloroform (nontargeted metabolomics), MeOH (targeted analysis); 2-chlorobenzalanine | ACQUITY UPLC HSS T3 C18 | UPLC-Orbitrap | 31 metabolites | UPLC-QQQ-MS | 17 metabolites in arachidonic acid metabolism | Inflammation related genes in ileum | Fecal 16S rRNA Seq | Dai et al. (2022) [292] |
| TRAP, N/A | Human plasma, saliva | ACN; N/A | HILIC column (pos ionization mode), C18 column (negionization mode) | UPLC-Q-Exactive | 1291 associated features | - | - | - | - | Liang et al. (2018) [293] |
| TRAP, N/A | Human plasma | ACN; 14 isotopic labeled ISs | C18 column | UPLC-Q-Exactive | 5112 associated features | - | - | - | - | Li et al. (2021) [294] |
N/A: no information provided.