基于非靶向代谢组学的活动性肺结核潜在生物标志物研究

doi:10.3969/j.issn.1006-5725.2026.07.005

Abstract

Abstract:

Objective To analyze the fecal metabolic profile of active tuberculosis（ATB） patients in order to explore novel non-invasive diagnostic biomarkers. Methods A total of 33 treatment-naive ATB patients（TB group） and 30 healthy controls（HC group） were recruited. Fresh fecal specimens from both groups were examined using UHPLC-MS-based untargeted metabolomics. Differential metabolites were selected by partial least squares discriminant analysis（PLS-DA） with the thresholds of variable importance in projection（VIP） ≥ 1.0， |log? FC| ≥ 0.585 （1.5-fold change）， and P ≤ 0.05. Potential biomarkers were recognized through KEGG pathway enrichment and clustering analyses， and their diagnostic effectiveness was assessed via receiver operating characteristic（ROC） curves. Results A total of 515 differential metabolites were identified （312 in ESI-； 203 in ESI+）， which were primarily enriched in purine metabolism， bile secretion， and nicotinate/nicotinamide metabolism. In the ESI- mode， 16 out of the top 20 metabolites were significantly down-regulated in the TB group， whereas PGE?， N-｛3-［（3，5-difluorophenyl）oxy］pyridin-2-yl｝-4-pentylbenzenesulfonamide， N'-2-acetylpyridine-2-carbohydrazone， and 5-hydroxyindole-2-carboxylic acid were up-regulated. In the ESI+ mode， 18 out of the top 20 metabolites were up-regulated， while 3-acetyl-2，5-dimethylfuran and fumaric acid were down-regulated. Metabolic pathway analysis combined with functional prediction identified three potential biomarkers—prostaglandin E₂（PGE₂）， trans-2-Butene-1，4-dicarboxylic Acid， and 5-hydroxyindole-2-carboxylic acid， with areas under the curve（AUC） of 0.911， 0.859， and 0.824， respectively. The logistic regression model integrating these three biomarkers achieved an AUC of 0.957 for combined diagnosis. Conclusions Differential metabolites in patients with active pulmonary tuberculosis were mainly enriched in purine metabolism， bile secretion， and nicotinate and nicotinamide metabolism pathways. Both PGE₂， trans-2-Butene-1，4-dicarboxylic acid， 5-hydroxyindole-2-carboxylic acid， and their combined diagnostic model showed good diagnostic efficacy for pulmonary tuberculosis.

Key words: active tuberculosis, untargeted metabolomics, feces, biomarkers

CLC Number:

R446.1

Yuan WANG,Zijie CHEN,Jieqing ZHONG,Yujie MO,Xiaoling QIN,Dongxu LIANG,Xiaojing GUO,Shiyi CHEN,Dan LUO. Untargeted metabolomics-based discovery of potential biomarkersfor active pulmonary tuberculosis[J]. The Journal of Practical Medicine, 2026, 42(7): 1149-1157.

Figures/Tables 6

Fig.1

Fig.2

Fig.3

Fig.4

Tab.1

Differential metabolites between TB and HC groups in ESI+ and ESI- modes"

离子模式	代谢物ID	代谢物名称	RT	m/z	FC	P值	ROC	VIP	变化趋势
ESI-	Com_124_neg	Prostaglandin E₂	6.2	775.4	263.0	0.000	0.911	2.25	up
ESI-	Com_3762_neg	N-{3-[(3,5-difluorobenzyl)oxy]pyridin-2-yl}-4-pentylbenzenesulfonamide	6.2	387.2	14.1	0.000	0.867	1.98	up
ESI-	Com_6897_neg	Bicyclo Prostaglandin E₂	6.3	445.1	0.3	0.000	0.908	1.93	down
ESI-	Com_15108_neg	N'2-acetylpyridine-2-carbohydrazide	6.0	369.2	11.6	0.000	0.805	1.91	up
ESI-	Com_4303_neg	Indole-3-carboxaldehyde	1.7	178.1	0.3	0.000	0.883	1.90	down
ESI-	Com_21058_neg	LysoPC 12∶1	5.7	144.0	0.1	0.000	0.880	1.89	down
ESI-	Com_33924_neg	LPE 16∶1	6.0	432.2	0.1	0.000	0.823	1.89	down
ESI-	Com_23451_neg	LPE 12∶0	9.0	450.3	0.3	0.000	0.889	1.84	down
ESI-	Com_23000_neg	12-oxo Phytodienoic Acid	7.6	396.2	0.3	0.000	0.849	1.84	down
ESI-	Com_48434_neg	LPC 20∶4	7.1	291.2	0.4	0.000	0.884	1.84	down
ESI-	Com_5014_neg	Kynurenic acid	5.4	188.0	0.3	0.000	0.869	1.79	down
ESI-	Com_16290_neg	D-Mannose 6-phosphate	1.3	259.0	0.1	0.000	0.859	1.79	down
ESI-	Com_6281_neg	D-Fructose 6-phosphate	1.6	259.0	0.1	0.000	0.769	1.79	down
ESI-	Com_5932_neg	2'-Deoxyadenosine 5'-monophosphate	1.9	330.1	0.1	0.000	0.858	1.78	down
ESI-	Com_3698_neg	tetranor-PGFM	5.5	311.2	0.2	0.000	0.840	1.77	down
ESI-	Com_22913_neg	4-chloro-2-（1H-pyrazol-3-yl）phenol	3.5	193.0	0.1	0.000	0.846	1.77	down
ESI-	Com_20624_neg	O-Aceyl-L-Serine	5.1	146.0	0.3	0.000	0.852	1.75	down
ESI-	Com_262_neg	Chenodeoxycholic Acid	8.0	437.3	0.6	0.001	0.735	1.73	down
ESI-	Com_756_neg	5-Hydroxyindole-2-carboxylic acid	2.4	176.0	4.5	0.000	0.824	1.73	up
ESI-	Com_20282_neg	Tetrahydroaldosterone	7.1	363.2	0.4	0.000	0.843	1.71	down
ESI+	Com_23170_pos	17alpha-Ethinyl estradiol	8.4	297.2	60.0	0.000	0.930	2.35	up
ESI+	Com_39105_pos	Biochanin A	6.2	285.1	7.9	0.000	0.929	2.33	up
ESI+	Com_11950_pos	Hesperetin	6.1	303.1	8.6	0.000	0.914	2.31	up
ESI+	Com_20745_pos	Isobutyl benzoate	8.5	179.1	11.7	0.000	0.878	2.15	up
ESI+	Com_11685_pos	Diosmetin	6.1	301.1	5.6	0.000	0.863	2.13	up
ESI+	Com_47294_pos	Apigenin	6.1	271.1	14.5	0.000	0.895	2.09	up
ESI+	Com_40745_pos	4'，7-Dihydroxyflavanone	6.1	240.1	4.5	0.000	0.873	2.08	up
ESI+	Com_16978_pos	Citrinin	6.1	273.1	5.9	0.000	0.888	2.06	up
ESI+	Com_45820_pos	3-Acetyl-2，5-dimethylfuran	6.4	121.1	0.6	0.000	0.882	2.05	down
ESI+	Com_30139_pos	Obacunoic acid	6.2	473.2	4.2	0.000	0.844	2.01	up
ESI+	Com_12081_pos	Purpurin	6.1	257.0	8.1	0.000	0.816	2.00	up
ESI+	Com_48551_pos	PC（6∶0/7∶0）	8.5	468.3	6.4	0.000	0.841	1.94	up
ESI+	Com_47889_pos	trans-2-Butene-1，4-dicarboxylic Acid	4.9	145.0	0.6	0.000	0.859	1.94	down
ESI+	Com_30106_pos	dAMP	6.2	332.1	5.3	0.000	0.813	1.90	up
ESI+	Com_52559_pos	ACar 22∶3	6.2	478.4	5.7	0.000	0.820	1.89	up
ESI+	Com_20558_pos	ACar 20∶6	6.2	444.3	5.1	0.000	0.827	1.89	up
ESI+	Com_6511_pos	Coenzyme Q1	6.1	251.1	2.8	0.000	0.836	1.87	up
ESI+	Com_19938_pos	（1R，2R）-trans-N-Boc-1，2-cyclohexanediamine	4.8	215.2	175.8	0.000	0.751	1.87	up
ESI+	Com_48630_pos	2，6-Di-tert-butyl-1，4-benzoquinone	6.2	221.2	3.7	0.000	0.821	1.86	up
ESI+	Com_17888_pos	3，4-Dimethylbenzoic acid	8.6	151.1	6.6	0.000	0.823	1.85	up

Tab.1

Fig.5

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Untargeted metabolomics-based discovery of potential biomarkersfor active pulmonary tuberculosis

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