. 2020 Apr 22;11:502. doi: 10.3389/fphar.2020.00502

Table 1.

Metabolomic-based potential biomarkers of sepsis and the levels change of metabolites responding to three different interventions.

No.	Metabolites	Theoretical mass (m/z)	Measured mass (m/z)	Delta (ppm)	RT (min)	Ion Mode	VIP	Fold Change (Model/Sham)	Fold Change (XBJ/Model)	Fold Change (BIPM/Model)	Fold Change (COM/Model)	Classification
1	Lactic acid^#	89.02441	89.02436	-0.644	1.15	n	1.63	1.83↑^**	0.55↓^**	0.55↓^**	0.59↓^**	Organic acids
2	Choline	104.10699	104.10700	0.090	0.88	p	1.42	2.15↑^*	–	0.53↓^*	0.51↓^*	Organonitrogen compounds
3	Glyceric acid	105.01933	105.01932	-0.114	1.14	n	1.12	1.57↑^*	–	–	–	Organic acids
4	Cytosine	112.05053	112.05052	-0.164	0.88	p	1.47	1.81↑^**	–	0.71↓^*	0.74↓^*	Pyrimidines
5	Uracil	113.03455	113.03449	-0.566	1.14	p	1.37	3.41↑^*	–	–	–	Pyrimidines
6	Creatinine^#	114.06618	114.06629	0.890	0.86	p	1.36	1.48↑^**	–	–	0.65↓^**	other
7	2-Oxovaleric acid	115.04006	115.03997	-0.847	2.48	n	1.24	1.34↑^**	–	–	–	Organic acids
8	Betaine^#	118.08625	118.08626	0.041	0.89	p	1.18	0.44↓^**	–	–	–	other
9	Nicotinamide^#	123.05528	123.05530	0.086	1.14	p	1.14	0.54↓^*	–	–	1.78↑^*	other
10	Pyroglutamic acid^†	130.04986	130.05000	1.002	0.89	p	1.60	1.47↑^**	0.72↓^**	0.71↓^**	0.75↓^*	Amino acids
11	4-Oxoproline^†	128.03531	128.03531	-0.050	1.15	n	1.56	1.74↑^**	0.67↓^*	0.59↓^**	0.63↓^**	Amino acids
12	Pipecolic acid	130.08625	130.08636	0.806	0.88	p	1.35	1.55↑^**	–	–	–	Amino acids
13	Creatine^#	132.07675	132.07684	0.658	0.87	p	1.72	2.45↑^**	–	0.64↓^*	0.49↓^**	Organic acids
14	2-hydroxycaproic acid	131.07136	131.07121	-1.202	3.98	n	1.16	1.85↑^*	–	0.57↓^*	0.58↓^*	Organic acids
15	Threonic acid	135.02989	135.02983	-0.493	0.90	n	1.71	1.77↑^**	–	0.58↓^**	0.60↓^**	Organic acids
16	3-Dehydroxycarnitine	146.11755	146.11763	0.511	0.90	p	1.52	1.58↑^**	–	–	0.69↓^**	other
17	Glutamine^#†	147.07641	147.07649	0.485	0.89	p	1.58	1.49↑^**	0.71↓^**	0.72↓^**	0.70↓^**	Amino acids
18	β-Ureidoisobutyric acid^†	147.07641	147.07652	0.689	0.89	p	1.50	1.46↑^**	0.73↓^*	0.72↓^**	0.72↓^**	Organic acids
19	Lysine^#	147.11280	147.11284	0.243	0.75	p	1.40	1.58↑^**	–	–	0.68↓^**	Amino acids
20	Glutamate^#†	146.04588	146.04597	0.609	0.90	n	1.33	1.81↑^*	0.57↓^*	0.55↓^*	0.64↓^*	Amino acids
21	Methionine^#†	150.05832	150.05843	0.694	1.14	p	1.70	1.64↑^**	–	0.73↓^**	0.69↓^**	Amino acids
22	Allantoin^†	157.03671	157.03656	-0.977	0.90	n	1.12	1.58↑^*	0.58↓^*	–	0.62↓^*	other
23	3-Dehydrocarnitine	158.08226	158.08223	-0.231	3.89	n	1.07	0.30↓^*	–	–	–	other
24	2-Hydroxycinnamic acid^#	165.05462	165.05475	0.784	1.16	p	1.04	1.36↑^*	–	0.71↓^*	0.76↓^*	Organic acids
25	Phenylalanine^#†	166.08625	166.08633	0.451	1.95	p	1.07	1.34↑^*	–	0.66↓^*	0.70↓^*	Amino acids
26	Uric acid^#^†	169.03561	169.03566	0.257	1.14	p	1.42	6.08↑^*	0.30↓^*	–	0.26↓^*	Organic acids
27	1-Methylhistidine	170.09240	170.09254	0.805	0.77	p	1.55	2.54↑^*	–	0.59↓^*	0.44↓^**	Amino acids
28	Hippuric acid^#†	178.05096	178.05099	0.132	3.73	n	1.32	0.19↓^**	–	–	2.45↑^*	Organic acids
29	Inositol	179.05611	179.05617	0.328	0.94	n	1.15	0.63↓^*	–	–	1.56↑^*	other
30	Tyrosine^#†	182.08116	182.08131	0.770	1.15	p	1.04	1.36↑^*	–	0.71↓^*	0.76↓^*	Amino acids
31	Phosphorylcholine	184.07332	184.07318	-0.766	7.96	p	1.45	0.71↓^**	–	1.31↑^*	1.41↑^**	Organonitrogen compounds
32	5-Hydroxyisourate	183.01597	183.01587	-0.590	1.14	n	1.53	4.99↑^*	0.42↓^*	0.39↓^*	0.36↓^**	Organic acids
33	Indoleacrylic acid	186.05605	186.05608	0.151	5.18	n	1.19	0.15↓^**	2.62↑^*	–	4.56↑^*	Indole derivatives
34	N6,N6,N6-Trimethyl-L-lysine	189.15975	189.15982	0.347	0.80	p	1.58	2.29↑^**	–	0.45↓^**	0.52↓^**	Amino acids
35	Citric acid^#	191.01972	191.01987	0.755	1.12	n	1.15	0.47↓^*	–	1.81↑^*	1.90↑^*	Organic acids
36	Acetyl-L-carnitine^#	204.12303	204.12308	0.223	1.13	p	1.35	1.45↑^**	–	–	0.60↓^**	Acyl carnitine
37	Lipoic acid	207.05079	207.05067	-0.617	0.79	p	1.71	2.39↑^**	0.69↓^*	0.70↓^*	0.54↓^**	Organic acids
38	N-Acetyl-L-phenylalanine^†	206.08226	206.08238	0.550	4.40	n	1.08	0.61↓^*	–	–	–	Amino acids
39	3-Oxododecanoic acid	213.14961	213.14978	0.761	6.98	n	1.44	4.16↑^*	0.38↓^*	–	0.40↓^*	Free fatty acids
40	12-Hydroxydodecanoic acid	215.16526	215.16531	0.196	7.49	n	1.06	1.86↑^*	–	–	–	Free fatty acids
41	Prolylleucine	229.15466	229.15454	-0.563	0.90	p	1.26	2.75↑^*	–	–	–	Amino acids
42	Pseudouridine^†	243.06225	243.06239	0.538	0.90	n	1.43	1.86↑^**	–	0.65↓^*	0.59↓^*	other
43	3-hydroxybutyrylcarnitine	248.14924	248.14923	-0.078	1.15	p	1.13	1.53↑^*	–	–	0.56↓^**	Acyl carnitine
44	Hexanoylcarnitine	260.18563	260.18576	0.481	4.37	p	1.68	3.01↑^**	0.73↓^*	0.54↓^*	0.40↓^**	Acyl carnitine
45	Neuraminic acid^†	266.08813	266.08823	0.339	0.88	n	1.71	3.03↑^**	–	0.54↓^*	0.34↓^**	Organic acids
46	His-asp	269.08914	269.08789	-4.656	0.89	n	1.63	2.37↑^**	0.55↓^*	0.45↓^**	0.44↓^**	Amino acids
47	Juniperic acid	271.22786	271.22806	0.707	9.67	n	1.48	1.54↑^**	0.82↓^*	–	0.74↓^*	Free fatty acids
48	Methyl aspartylphenylalaninate^†	295.12884	295.12888	0.108	3.53	p	1.40	1.79↑^*	–	0.59↓^*	0.55↓^*	Amino acids
49	Sphingosine^#	300.28970	300.28952	-0.619	7.32	p	1.21	0.32↓^**	2.16↑^**	–	2.77↑^*	Sphingolipids
50	Sphinganine	302.30535	302.30524	-0.384	7.08	p	1.30	0.75↓^**	1.16↑^*	–	1.24↑^*	Sphingolipids
51	Arachidonic acid^#	303.23295	303.23315	0.648	9.78	n	1.21	1.30↑^**	0.81↓^*	–	0.83↓^*	Free fatty acids
52	N-Acetylneuraminic acid	308.09870	308.09891	0.668	0.95	n	1.70	7.06↑^**	–	0.37↓^*	0.20↓^**	Organic acids
53	Docosahexaenoic acid^#	327.23295	327.23325	0.906	9.62	n	1.50	1.94↑^**	0.74↓^*	–	0.64↓^*	Free fatty acids
54	Trihydroxy octadecenoic acid	329.23334	329.23315	-0.600	5.90	n	1.36	2.41↑^*	0.44↓^*	0.41↓^*	0.56↓^*	Free fatty acids
55	Docosapentaenoic acid^#	329.24860	329.24881	0.627	10.02	n	1.08	1.99↑^*	0.53↓^*	–	0.58↓^*	Free fatty acids
56	3-Indole carboxylic acid glucuronide^†	336.07248	336.07285	1.072	3.61	n	1.05	0.08↓^*	–	–	5.13↑^*	other
57	5-Hydroxy-6-methoxyindole glucuronide^†	338.08813	338.08853	1.154	3.86	n	1.28	0.07↓^**	–	–	–	other
58	N-Acetyl-4-O-Acetylneuraminate^†	350.10926	350.10959	0.917	1.15	n	1.52	11.90↑^*	–	–	0.11↓^*	Organic acids
59	Tetradecenoylcarnitine	370.29518	370.29489	-0.797	7.05	p	1.23	2.04↑^**	1.60↑^*	–	–	Acyl carnitine
60	Ursodeoxycholic acid^†	391.28538	391.28583	1.142	7.02	n	1.37	3.05↑^**	0.41↓^*	–	0.36↓^**	Bile acids
61	Deoxycholic acid^#†	391.28538	391.28580	1.066	7.65	n	1.21	3.21↑^**	0.31↓^*	–	0.31↓^*	Bile acids
62	Hexadecenoylcarnitine	398.32648	398.32642	-0.164	7.54	p	1.42	2.15↑^**	0.72↓^*	–	0.64↓^*	Acyl carnitine
63	Palmitoylcarnitine^#	400.34213	400.34189	-0.613	7.94	p	1.45	2.23↑^**	0.74↓^*	–	0.60↓^*	Acyl carnitine
64	Linoleyl carnitine	424.34213	424.34198	-0.366	7.70	p	1.37	1.87↑^**	0.76↓^*	0.68↓^*	0.66↓^*	Acyl carnitine
65	Oleoylcarnitine	426.35778	426.35764	-0.341	8.04	p	1.37	2.28↑^**	–	–	–	Acyl carnitine
66	Stearoylcarnitine	428.37343	428.37335	-0.200	8.40	p	1.48	2.63↑^**	–	–	–	Acyl carnitine
67	Chenodeoxyglycocholic acid^†	448.30684	448.30734	1.100	6.83	n	1.44	4.79↑^**	0.37↓^*	–	0.31↓^**	Bile acids
68	LysoPE(18:0)^†	482.32411	482.32391	-0.427	8.05	p	1.22	0.31↓^**	–	1.89↑^*	2.85↑^**	Glycerophospholipids
69	LysoPC(O-16:0)	482.36050	482.36060	0.205	8.73	p	1.10	0.80↓^*	–	1.34↑^*	1.32↑^*	Glycerophospholipids
70	LysoPC(16:0)	496.33976	496.33972	-0.092	8.49	p	1.21	0.79↓^**	–	–	1.16↑^*	Glycerophospholipids
71	LysoPE(20:4)^†	502.29281	502.29251	-0.609	8.07	p	1.31	1.57↑^**	–	–	0.69↓^*	Glycerophospholipids
72	LysoPE(20:3)^†	504.30846	504.30826	-0.408	8.38	p	1.17	0.21↓^*	–	–	3.74↑^**	Glycerophospholipids
73	LysoPC(17:0)	510.35541	510.35541	-0.012	8.93	p	1.48	0.45↓^**	1.17↑^*	1.55↑^*	2.13↑^**	Glycerophospholipids
74	LysoPC(18:3)	518.32411	518.32416	0.085	7.73	p	1.34	0.75↓^**	–	–	–	Glycerophospholipids
75	LysoPC(18:2)	520.33976	520.33984	0.143	8.11	p	1.36	0.68↓^**	–	–	1.38↑^*	Glycerophospholipids
76	LysoPC(18:1)	522.35541	522.35553	0.218	8.68	p	1.16	0.66↓^*	1.27↑^*	1.28↑^*	1.50↑^*	Glycerophospholipids
77	LysoPE(22:6)^†	526.29281	526.29272	-0.182	8.02	p	1.13	0.75↓^*	1.98↑^**	1.64↑^*	1.74↑^**	Glycerophospholipids
78	LysoPC(20:5)	542.32411	542.32410	-0.029	7.64	p	1.41	0.68↓^**	–	1.27↑^*	1.31↑^*	Glycerophospholipids
79	LysoPC(20:4)	544.33976	544.33936	-0.746	8.09	p	1.68	0.65↓^**	–	1.35↑^**	1.43↑^**	Glycerophospholipids
80	LysoPC(20:2)	548.37106	548.37091	-0.284	8.86	p	1.21	0.42↓^**	1.34↑^*	1.63↑^*	2.25↑^*	Glycerophospholipids
81	Taurolithocholic acid-3-sulfate	562.25138	562.25158	0.356	13.50	n	1.74	13.29↑^**	–	–	–	Bile acids
82	LysoPC(22:4)	572.37106	572.37103	-0.063	8.70	p	1.23	0.60↓^**	1.27↑^*	1.34↑^*	1.52↑^**	Glycerophospholipids
83	LysoPI(20:4)	619.28888	619.28912	0.377	13.50	n	1.66	0.52↓^**	1.61↑^**	1.51↑^*	1.62↑^*	Glycerophospholipids
84	PC(16:0/18:2)	758.56943	758.56940	-0.041	13.42	p	1.29	1.51↑^**	–	–	–	Glycerophospholipids
85	PC(16:0/18:1)	760.58508	760.58337	-2.250	13.48	p	1.50	0.38↓^**	–	–	–	Glycerophospholipids
86	PC(18:3/18:2)	780.55378	780.55139	-3.064	13.42	p	1.39	2.38↑^*	–	–	0.63↓^*	Glycerophospholipids
87	PC(18:1/18:2)	784.58508	784.58270	-3.035	13.52	p	1.62	4.31↑^**	0.54↓^*	0.61↓^*	0.61↓^*	Glycerophospholipids
88	PC(18:0/18:2)	786.60073	786.60071	-0.027	13.44	p	1.25	1.56↑^**	0.81↓^*	0.75↓^*	0.82↓^*	Glycerophospholipids
89	PC(16:0/22:6)	806.56943	806.56696	-3.064	13.42	p	1.08	1.21↑^*	–	–	–	Glycerophospholipids
90	PC(16:0/22:5)	808.58508	808.58246	-3.242	13.41	p	1.24	1.91↑^**	0.69↓^*	0.71↓^*	0.67↓^*	Glycerophospholipids
91	PC(18:0/22:6)	834.60073	834.60034	-0.469	13.53	p	1.39	3.12↑^*	–	–	–	Glycerophospholipids

^#metabolites were identified by reference standards; ^†metabolites were detected in both negative and positive ion modes; ^*p values < 0.05; ^**p values < 0.01; RT, retention time; VIP, variable importance in the projection obtained from Model group vs. Sham group; XBJ, xuebijing injection; BIPM, biapenem; COM, combination of xuebijing injection and biapenem; LysoPE, lysophosphatidylethanolamine; LysoPC, lysophosphatidylcholine; LysoPI, lysophosphatidylinositol; PC, phosphatidylcholine; p, positive ion mode; n, negative ion mode.