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METABOLOMIC BIOMARKERS OF INFLAMMATORY BOWEL DISEASE AND ITS DAMP HEAT SYNDROME IN COMPARING WITH FUNCTIONAL DIARRHEA OF CHINESE PATIENTS AND HEALTHY CONTROLS--- PRELIMINARY FINDINGS

JING WU 1, Xingxing Wu 2, Yuge Li 3, Qi WU 3

Affiliations

1 Nanjing University, Nanjing Drum Tower Hospital, Drum Tower Clinical Medicine College of Nanjing University of Chinese Medicine, Nanjing, China

2 Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou, China

3 Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China

Summary

AI Generated

Pseudotargeted metabolomics analysis of 60 IBD patients identified distinct plasma and urine metabolite profiles differentiating active IBD from healthy controls, functional diarrhea, and distinguishing traditional Chinese medicine syndrome subtypes.

In IBD versus healthy controls, 73 plasma and 98 urine differential metabolites were identified, with increased acylcarnitines (ACar 16:1, ACar 18:1, ACar 20:4), LPC P-18:0, and malate, and decreased PC 33:3, glycocholic acid, hippuric acid, and p-cresol; L-glutamic acid, ACar 18:1, and lactic acid emerged as potential IBD diagnostic biomarkers.
Comparing IBD to functional diarrhea, 48 plasma and 69 urine differential metabolites were found, predominantly fatty acids, acylcarnitines, aromatic amino acid metabolites, bile acids, and glycerophospholipids; ACar 6:0 and 5b-cholestane-3a,7a,12a,24,25-pentanol showed potential to differentiate organic IBD from functional diarrhea.
Between IBD damp heat syndrome and spleen deficiency syndrome, 28 plasma and 15 urine differential metabolites were identified, with aromatic amino acids and glycerophospholipids predominating; indolelactate, tyramine, L-tryptophan, LPC 16:0-2, PC 38:7-sn1, and itaconic acid distinguished the two syndrome subtypes.
This study recruited 60 active IBD patients, 23 functional diarrhea patients, and 30 healthy volunteers from May 2020 to July 2021, using ultra-high performance liquid chromatography-high-resolution mass spectrometry and triple-quadrupole mass spectrometry for metabolomic profiling.

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Abstract

Introduction

The specific and sensitive biomarkers of inflammatory bowel disease (IBD) had not been found.

Aims & Methods

The aim of this study was to observe the metabolic characteristics of IBD patients and its damp heat syndrome (IBD-DH).
From May 2020 to July 2021 at Affiliated Hospital of Nanjing University of Chinese Medicine, patients with active inflammatory bowel disease (IBD), including damp heat syndrome (IBD-DH) and spleen-deficiency syndrome (IBD-SD), functional diarrhea patients (FD), and healthy volunteers (Con) were recruited. Fasting venous plasma and 2nd urine were collected from all patients and healthy volunteers; Using pseudotargeted metabolomics based on ultra-high performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) and triple-quadrupole mass spectrometry (TQMS).

Results

A total of 60 patients with IBD (30 each in damp heat and spleen deficiency syndrome group), 23 patients with functional diarrhea, and 30 healthy volunteers were recruited in this study. A total of 60 plasma samples (30 IBD-DH and 30 IBD-SD) and 30 urine samples (15 each in IBD-DH and IBD-SD ) were collected for IBD patients; 23 plasma samples and 20 urine samples from FD patients; 30 plasma samples and 15 urine samples from healthy volunteers.
In the IBD group compared with the Con group, 73 and 98 differential metabolites were screened in plasma and urine, respectively. The differential metabolites mainly included acylcarnitine, aromatic amino acid metabolites, glycerophospholipids, amino acids, and glucose metabolism intermediates. Abundance of ACar 16:1, ACar 18:1, ACar 20:4, LPC P-18:0 and malate increased significantly; abundance of PC 33:3, glycocholic acid, hippuric acid, p-cresol and p-cresol sulfate decreased significantly. Differential metabolite ROC analysis suggested L-glutamic acid, ACar 18:1, and Lactic acid as potential diagnostic biomarkers for IBD.
Forty-eight plasma differential metabolites and 69 urinary differential metabolites were obtained in the IBD group compared with the FD group. The differential metabolites mainly included fatty acids, acylcarnitine, aromatic amino acid metabolites, bile acids, and glycerophospholipids. The abundance of ACar 6:0, PC 24:0, 5b-cholestane-3a,7a,12a,24,25-pentanol, and 3-methoxybenzenediol in plasma was significantly decreased; the abundance of glycocholicacid and glycochenodeoxycholic was increased. The abundance of corticosterone, 5-hydroxy-N-formyl-kynurenine and other substances in the urine was significantly decreased. By ROC analysis, ACar 6:0, 5b-cholestane-3a,7a,12a,24,25-pentanol were found to be potential diagnostic markers to differentiate IBD from FD.
28 differential metabolites in plasma and 15 differential metabolites in urine were found .The abundance of 25 substances, including PC 16:1_20:4, PC 18:0_20:4, LPC 16:0-2, LPC 3:1, L-tryptophan, tyramine, and 3-hydroxybutyrate, increased in plasma; the abundance of indolelactic acid was decreased. By ROC analysis, indolelactate, tyramine, L-tryptophan, LPC 16:0-2, PC 38:7-sn1, and itaconic acid were found to distinguish IBD-SD and IBD-DH and were expected to be potential diagnostic biomarkers for IBD-DH.

Conclusion

As an organic lesion closely related to inflammation and immunity, IBD had prominent changes in the abundance of plasma ACar 6:0, 5b-cholestane-3a,7a,12a,24,25-pentanol in comparing with FD, a functional disease of the intestine. In terms of different syndromes, The differential metabolites mainly include aromatic amino acids and glycerophospholipids could be used to distinguish damp heat syndrome from spleen deficiency syndrome.

Disclosure

No Conflict of Interest to be declared

Conference

UEG Week Copenhagen 2023

Topics

IBD

Submission format

Abstract

Session

PP 05 IBD (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

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NOVEL BIOMARKERS ASSOCIATED WITH INFLAMMATORY BOWEL DISEASE

Montse Baldan Martin 1, Ibon Iloro 2, Mikel Azkargorta 2, Macarena Orejudo del Río 1, Cristina Ramírez 1, Irene Soleto 1, Jore Mercado 1, Fabio Suarez-Trujillo 1, Cristina Sánchez Sánchez 1, Carlos H. Gordillo 3, Ruth María de Francisco García 4, Montserrat Rivero 5, Ana Gutiérrez-Casbas 6, Iago Rodríguez-Lago 7, Luis Fernández-Salazar 8, Daniel Sebastian Ceballos Santos 9, JOSE MANUEL BENITEZ CANTERO 10, Mariam Aguas 11, Iria Bastón-Rey 12, Fernando Bermejo 13, María José Casanova 1, Rufo Lorente Poyatos 14, Yolanda Ber Nieto 15, Vanesa Royo Escosa 16, Maria Esteve Comas 17, Felix Elortza 2, Javier P. Gisbert 1, María Chaparro 1

Affiliations

1 Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Spain

2 Proteomics Platform, CIC bioGUNE, BRTA (Basque Research & Technology Alliance), CIBERehd, Derio, Spain

3 Hospital Universitario de La Princesa, Madrid, Spain

4 Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain

5 Hospital Universitario Marqués de Valdecilla and IDIVAL, Santander, Spain

6 Hospital General Universitario Alicante, CIBERehd and Instituto de Investigación Sanitaria y Biomédica de Alicante, Alicante, Spain

7 Hospital Galdakao-Usansolo, Vizcaya, Spain

8 Hospital Clínico Universitario de Valladolid, Valladolid, Spain

9 Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain

10 Hospital Universitario Reina Sofía and IMIBIC, Córdoba, Spain

11 Hospital Universitari i Politecnic La Fe and Health Research Institute (IISLaFe), Valencia, Spain

12 Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain

13 Hospital Universitario de Fuenlabrada, Madrid, Spain

14 Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

15 Hospital San Jorge, Huesca, Spain

16 Hospital Universitari Son Espases, Palma de Mallorca, Spain

17 Hospital Universitari Mutua Terrassa and CIBERehd, Barcelona, Spain