Objective
The clinical symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) can be effectively improved by traditional Chinese medicine (TCM) treatment, based on the usage of specific therapies for different TCM syndromes. However, in the stage of diagnosis, the standard criteria for the classification of TCM syndrome were still deficient. Through serum metabolic profiling, this study aimed to explore potential biomarkers in IBS-D patients with different TCM syndromes, which can assist in diagnosis of the disease.

Methods
Serum samples were collected from healthy controls (30 cases), IBS-D patients with Liver-Stagnation and Spleen-Deficiency syndrome (LSSD, 30 cases), Yang Deficiency of Spleen and Kidney syndrome (YDSK, 11 cases) and Damp Abundance due to Spleen-Deficiency syndrome (DASD, 22 cases). Serum metabolic profiling was conducted by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The potential biomarkers were screened by orthogonal partial least square-discriminate analysis, while metabolic pathways undergoing alterations were identified by pathway enrichment analysis in MetaboAnalyst 4.0.

Results
Overall, 34 potential biomarkers were identified in LSSD group, 36 in YDSK group and 31 in DASD group. And the 13 metabolites shared by three groups were determined as the potential biomarkers of IBS-D. Glycerophospholipid metabolism was disturbed significantly in IBS-D patients, which may play a role in IBS-D through inflammation. What’s more, three TCM syndromes have the specific potential biomarkers in glycerophospholipid metabolism.

Conclusion
The serum metabolomics revealed that different TCM syndrome types in IBS-D may have different metabolic patterns during disease progression and glycerophospholipid metabolism was one of the pathways, whose metabolism was disturbed differently among three TCM syndromes in IBS-D. Therefore, the specific potential biomarkers in glycerophospholipid metabolism of three TCM syndromes in IBS-D can serve as the objective indicators, which can facilitate the TCM-syndrome objective classification of IBS-D.

Key words: Diarrhea, Irritable bowel syndrome, Metabolomics, Traditional Chinese medicine syndromes