Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Cohort
2.2. Irritable Bowel Syndrome Definition
IBS Subtype
2.3. Dietary Data
2.4. Medication Use
2.5. Metabolomics
2.6. Statistical Analysis
2.6.1. Statistical Modelling
2.6.2. Pathway Enrichment Analysis
3. Results
3.1. Descriptive Characteristics
3.2. Multi-Fluid IBS-Metabolite Associations
3.3. Fluid-Specific Associations
3.3.1. Urine Metabolites
3.3.2. Serum Metabolites
3.3.3. Stool Metabolites
3.4. Sensitivity Analysis
3.5. Subtype Analysis
3.6. Enrichment Analysis
4. Discussion
4.1. Metabolites Associated in Multiple Fluids
4.2. Tissue-Specific Associations
4.3. Androgen Signalling
4.4. Fatty Acids
4.5. Haemoglobin and Porphyrin Metabolism
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Black, C.J.; Ford, A.C. Global Burden of Irritable Bowel Syndrome: Trends, Predictions and Risk Factors. Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 473–486. [Google Scholar] [CrossRef] [PubMed]
- Saha, L. Irritable Bowel Syndrome: Pathogenesis, Diagnosis, Treatment, and Evidence-Based Medicine. World J. Gastroenterol. WJG 2014, 20, 6759. [Google Scholar] [CrossRef] [PubMed]
- Mayer, E.A.; Nance, K.; Chen, S. The Gut–Brain Axis. Annu. Rev. Med. 2022, 73, 439–453. [Google Scholar] [CrossRef] [PubMed]
- Holtmann, G.J.; Ford, A.C.; Talley, N.J. Pathophysiology of Irritable Bowel Syndrome. Lancet Gastroenterol. Hepatol. 2016, 1, 133–146. [Google Scholar] [CrossRef]
- Chong, P.P.; Chin, V.K.; Looi, C.Y.; Wong, W.F.; Madhavan, P.; Yong, V.C. The Microbiome and Irritable Bowel Syndrome—A Review on the Pathophysiology, Current Research and Future Therapy. Front. Microbiol. 2019, 10, 424646. [Google Scholar] [CrossRef]
- Lacy, B.E.; Patel, N.K. Rome Criteria and a Diagnostic Approach to Irritable Bowel Syndrome. J. Clin. Med. 2017, 6, 99. [Google Scholar] [CrossRef]
- Louca, P.; Meijnikman, A.S.; Nogal, A.; Asnicar, F.; Attaye, I.; Vijay, A.; Kouraki, A.; Visconti, A.; Wong, K.; Berry, S.E.; et al. The Secondary Bile Acid Isoursodeoxycholate Correlates with Post-Prandial Lipemia, Inflammation, and Appetite and Changes Post-Bariatric Surgery. Cell Rep. Med. 2023, 4, 100993. [Google Scholar] [CrossRef]
- Jeffery, I.B.; Das, A.; O’Herlihy, E.; Coughlan, S.; Cisek, K.; Moore, M.; Bradley, F.; Carty, T.; Pradhan, M.; Dwibedi, C.; et al. Differences in Fecal Microbiomes and Metabolomes of People With vs Without Irritable Bowel Syndrome and Bile Acid Malabsorption. Gastroenterology 2020, 158, 1016–1028.e8. [Google Scholar] [CrossRef]
- Jacobs, J.P.; Lagishetty, V.; Hauer, M.C.; Labus, J.S.; Dong, T.S.; Toma, R.; Vuyisich, M.; Naliboff, B.D.; Lackner, J.M.; Gupta, A.; et al. Multi-Omics Profiles of the Intestinal Microbiome in Irritable Bowel Syndrome and Its Bowel Habit Subtypes. Microbiome 2023, 11, 5. [Google Scholar] [CrossRef]
- Kirk, D.; Costeira, R.; Visconti, A.; Khan Mirzaei, M.; Deng, L.; Valdes, A.M.; Menni, C. Bacteriophages, Gut Bacteria, and Microbial Pathways Interplay in Cardiometabolic Health. Cell Rep. 2024, 43, 113728. [Google Scholar] [CrossRef]
- Valles-Colomer, M.; Menni, C.; Berry, S.E.; Valdes, A.M.; Spector, T.D.; Segata, N. Cardiometabolic Health, Diet and the Gut Microbiome: A Meta-Omics Perspective. Nat. Med. 2023, 29, 551–561. [Google Scholar] [CrossRef]
- Gowda, G.A.N.; Zhang, S.; Gu, H.; Asiago, V.; Shanaiah, N.; Raftery, D. Metabolomics-Based Methods for Early Disease Diagnostics. Expert Rev. Mol. Diagn. 2008, 8, 617–633. [Google Scholar] [CrossRef]
- Mars, R.A.T.; Yang, Y.; Ward, T.; Houtti, M.; Priya, S.; Lekatz, H.R.; Tang, X.; Sun, Z.; Kalari, K.R.; Korem, T.; et al. Longitudinal Multi-Omics Reveals Subset-Specific Mechanisms Underlying Irritable Bowel Syndrome. Cell 2020, 182, 1460. [Google Scholar] [CrossRef]
- Mujagic, Z.; Kasapi, M.; Jonkers, D.M.A.E.; Garcia-Perez, I.; Vork, L.; Weerts, Z.Z.R.M.; Serrano-Contreras, J.I.; Zhernakova, A.; Kurilshikov, A.; Scotcher, J.; et al. Integrated Fecal Microbiome-Metabolome Signatures Reflect Stress and Serotonin Metabolism in Irritable Bowel Syndrome. Gut Microbes 2022, 14, 2063016. [Google Scholar] [CrossRef]
- Tanaka, Y.; Yamashita, R.; Kawashima, J.; Mori, H.; Kurokawa, K.; Fukuda, S.; Gotoh, Y.; Nakamura, K.; Hayashi, T.; Kasahara, Y.; et al. Omics Profiles of Fecal and Oral Microbiota Change in Irritable Bowel Syndrome Patients with Diarrhea and Symptom Exacerbation. J. Gastroenterol. 2022, 57, 748–760. [Google Scholar] [CrossRef]
- Han, L.; Zhao, L.; Zhou, Y.; Yang, C.; Xiong, T.; Lu, L.; Deng, Y.; Luo, W.; Chen, Y.; Qiu, Q.; et al. Altered Metabolome and Microbiome Features Provide Clues in Understanding Irritable Bowel Syndrome and Depression Comorbidity. ISME J. 2022, 16, 983–996. [Google Scholar] [CrossRef]
- Yu, Q.; Liu, X.; Huang, H.; Zheng, X.; Pan, X.; Fang, J.; Meng, L.; Zhou, C.; Zhang, X.; Li, Z.; et al. Mass Spectrometry-Based Metabolomics for Irritable Bowel Syndrome Biomarkers. Ther. Adv. Gastroenterol. 2019, 12, 1756284819886425. [Google Scholar] [CrossRef]
- Yamamoto, M.; Pinto-Sanchez, M.I.; Bercik, P.; Britz-McKibbin, P. Metabolomics Reveals Elevated Urinary Excretion of Collagen Degradation and Epithelial Cell Turnover Products in Irritable Bowel Syndrome Patients. Metabolomics 2019, 15, 82. [Google Scholar] [CrossRef]
- Liu, T.; Liu, T.; Liu, T.; Gu, X.; Gu, X.; Gu, X.; Li, L.X.; Li, L.X.; Li, L.X.; Li, M.; et al. Microbial and Metabolomic Profiles in Correlation with Depression and Anxiety Co-Morbidities in Diarrhoea-Predominant IBS Patients. BMC Microbiol. 2020, 20, 168. [Google Scholar] [CrossRef]
- Verdi, S.; Abbasian, G.; Bowyer, R.C.E.; Lachance, G.; Yarand, D.; Christofidou, P.; Mangino, M.; Menni, C.; Bell, J.T.; Falchi, M.; et al. TwinsUK: The UK Adult Twin Registry Update. Twin Res. Hum. Genet. 2019, 22, 523–529. [Google Scholar] [CrossRef]
- Bingham, S.A.; Welch, A.A.; McTaggart, A.; Mulligan, A.A.; Runswick, S.A.; Luben, R.; Oakes, S.; Khaw, K.T.; Wareham, N.; Day, N.E. Nutritional Methods in the European Prospective Investigation of Cancer in Norfolk. Public Health Nutr. 2001, 4, 847–858. [Google Scholar] [CrossRef] [PubMed]
- Mulligan, A.A.; Luben, R.N.; Bhaniani, A.; Parry-Smith, D.J.; O’Connor, L.; Khawaja, A.P.; Forouhi, N.G.; Khaw, K.T. A New Tool for Converting Food Frequency Questionnaire Data into Nutrient and Food Group Values: FETA Research Methods and Availability. BMJ Open 2014, 4, e004503. [Google Scholar] [CrossRef]
- Mompeo, O.; Gibson, R.; Christofidou, P.; Spector, T.D.; Menni, C.; Mangino, M. Genetic and Environmental Influences of Dietary Indices in a UK Female Twin Cohort. Twin Res. Hum. Genet. 2020, 23, 330–337. [Google Scholar] [CrossRef]
- Camilleri, M. Management Options for Irritable Bowel Syndrome. Mayo Clin. Proc. 2018, 93, 1858. [Google Scholar] [CrossRef]
- Benjamini, Y.; Hochberg, Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J. R. Stat. Soc. Ser. B (Methodol.) 1995, 57, 289–300. [Google Scholar] [CrossRef]
- Attaye, I.; Beynon-Cobb, B.; Louca, P.; Nogal, A.; Visconti, A.; Tettamanzi, F.; Wong, K.; Michellotti, G.; Spector, T.D.; Falchi, M.; et al. Cross-Sectional Analyses of Metabolites across Biological Samples Mediating Dietary Acid Load and Chronic Kidney Disease. iScience 2024, 27, 109132. [Google Scholar] [CrossRef]
- Ford, L.; Kennedy, A.D.; Goodman, K.D.; Pappan, K.L.; Evans, A.M.; Miller, L.A.D.; Wulff, J.E.; Wiggs, B.R.; Lennon, J.J.; Elsea, S.; et al. Precision of a Clinical Metabolomics Profiling Platform for Use in the Identification of Inborn Errors of Metabolism. J. Appl. Lab. Med. 2020, 5, 342–356. [Google Scholar] [CrossRef]
- Bates, D.; Mächler, M.; Bolker, B.M.; Walker, S.C. Fitting Linear Mixed-Effects Models Using Lme4. J. Stat. Softw. 2015, 67, 1–48. [Google Scholar] [CrossRef]
- Wieder, C.; Frainay, C.; Poupin, N.; Rodríguez-Mier, P.; Vinson, F.; Cooke, J.; Lai, R.P.J.; Bundy, J.G.; Jourdan, F.; Ebbels, T. Pathway Analysis in Metabolomics: Recommendations for the Use of over-Representation Analysis. PLoS Comput. Biol. 2021, 17, e1009105. [Google Scholar] [CrossRef]
- Zhang, X.; Adebayo, A.S.; Wang, D.; Raza, Y.; Tomlinson, M.; Dooley, H.; Bowyer, R.C.E.; Small, K.S.; Steves, C.J.; Spector, T.D.; et al. PPI-Induced Changes in Plasma Metabolite Levels Influence Total Hip Bone Mineral Density in a UK Cohort. J. Bone Miner. Res. 2022, 38, 326. [Google Scholar] [CrossRef]
- Prospero, L.; Riezzo, G.; Linsalata, M.; Orlando, A.; D’Attoma, B.; Di Masi, M.; Martulli, M.; Russo, F. Somatization in Patients with Predominant Diarrhoea Irritable Bowel Syndrome: The Role of the Intestinal Barrier Function and Integrity. BMC Gastroenterol. 2021, 21, 235. [Google Scholar] [CrossRef] [PubMed]
- Keshteli, A.H.; Madsen, K.L.; Mandal, R.; Boeckxstaens, G.E.; Bercik, P.; De Palma, G.; Reed, D.E.; Wishart, D.; Vanner, S.; Dieleman, L.A. Comparison of the Metabolomic Profiles of Irritable Bowel Syndrome Patients with Ulcerative Colitis Patients and Healthy Controls: New Insights into Pathophysiology and Potential Biomarkers. Aliment. Pharmacol. Ther. 2019, 49, 723–732. [Google Scholar] [CrossRef] [PubMed]
- Zhao, L. Increased Bile Acid-Metabolizing Bacteria Contributes to Enhanced Gastrointestinal Motility in Irritable Bowel Syndrome. Ph.D. Thesis, Hong Kong Baptist University, Hong Kong, China, 2018. [Google Scholar]
- Sugaya, N.; Izawa, S.; Kimura, K.; Ogawa, N.; Yamada, K.C.; Shirotsuki, K.; Mikami, I.; Hirata, K.; Nagano, Y.; Nomura, S.; et al. Adrenal Hormone Response and Psychophysiological Correlates under Psychosocial Stress in Individuals with Irritable Bowel Syndrome. Int. J. Psychophysiol. 2012, 84, 39–44. [Google Scholar] [CrossRef] [PubMed]
- Chua, C.S.; Huang, S.Y.; Cheng, C.W.; Bai, C.H.; Hsu, C.Y.; Chiu, H.W.; Hsu, J.L. Fatty Acid Components in Asian Female Patients with Irritable Bowel Syndrome. Medicine 2017, 96, e9094. [Google Scholar] [CrossRef]
- Solakivi, T.; Kaukinen, K.; Kunnas, T.; Lehtimäki, T.; Mäki, M.; Nikkari, S.T. Serum Fatty Acid Profile in Subjects with Irritable Bowel Syndrome. Scand. J. Gastroenterol. 2011, 46, 299–303. [Google Scholar] [CrossRef]
- Chen, G.; Wu, X.; Zhu, H.; Li, K.; Zhang, J.; Sun, S.; Wang, H.; Wang, M.; Shao, B.; Li, H.; et al. Multisample Lipidomic Profiles of Irritable Bowel Syndrome and Irritable Bowel Syndrome-like Symptoms in Patients with Inflammatory Bowel Disease: New Insight into the Recognition of the Same Symptoms in Different Diseases. J. Gastroenterol. 2024, 59, 1000–1010. [Google Scholar] [CrossRef]
- Osadchiy, V.; Mayer, E.A.; Gao, K.; Labus, J.S.; Naliboff, B.; Tillisch, K.; Chang, L.; Jacobs, J.P.; Hsiao, E.Y.; Gupta, A. Analysis of Brain Networks and Fecal Metabolites Reveals Brain–Gut Alterations in Premenopausal Females with Irritable Bowel Syndrome. Transl. Psychiatry 2020, 10, 367. [Google Scholar] [CrossRef]
- Lee, J.S.; Kim, S.Y.; Chun, Y.S.; Chun, Y.J.; Shin, S.Y.; Choi, C.H.; Choi, H.K. Characteristics of Fecal Metabolic Profiles in Patients with Irritable Bowel Syndrome with Predominant Diarrhea Investigated Using 1 H-NMR Coupled with Multivariate Statistical Analysis. Neurogastroenterol. Motil. 2020, 32, e13830. [Google Scholar] [CrossRef]
- Hollister, E.B.; Oezguen, N.; Chumpitazi, B.P.; Luna, R.A.; Weidler, E.M.; Rubio-Gonzales, M.; Dahdouli, M.; Cope, J.L.; Mistretta, T.A.; Raza, S.; et al. Leveraging Human Microbiome Features to Diagnose and Stratify Children with Irritable Bowel Syndrome. J. Mol. Diagn. 2019, 21, 449–461. [Google Scholar] [CrossRef]
- Filimoniuk, A.; Daniluk, U.; Samczuk, P.; Wasilewska, N.; Jakimiec, P.; Kucharska, M.; Lebensztejn, D.M.; Ciborowski, M. Metabolomic Profiling in Children with Inflammatory Bowel Disease. Adv. Med. Sci. 2020, 65, 65–70. [Google Scholar] [CrossRef]
- Neef, S.K.; Janssen, N.; Winter, S.; Wallisch, S.K.; Hofmann, U.; Dahlke, M.H.; Schwab, M.; Mürdter, T.E.; Haag, M. Metabolic Drug Response Phenotyping in Colorectal Cancer Organoids by LC-QTOF-MS. Metabolites 2020, 10, 494. [Google Scholar] [CrossRef] [PubMed]
- Semba, R.D.; Trehan, I.; Li, X.; Moaddel, R.; Ordiz, M.I.; Maleta, K.M.; Kraemer, K.; Shardell, M.; Ferrucci, L.; Manary, M. Environmental Enteric Dysfunction Is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation. EBioMedicine 2017, 17, 57–66. [Google Scholar] [CrossRef]
- Sugaya, N.; Izawa, S.; Ogawa, N.; Shirotsuki, K.; Kobayashi, H.; Yamada, K.C.; Tsumura, H.; Nomura, S.; Shimada, H. Effect of Day-to-Day Variations in Adrenal Cortex Hormone Levels on Abdominal Symptoms. BioPsychoSocial Med. 2010, 4, 2. [Google Scholar] [CrossRef]
- Nelson, D.L.; Cox, M. Lehninger Principes of Biochemistry; W. H. Freeman: New York City, NY, USA, 2021; ISBN 9781319381493. [Google Scholar]
- De Vos, W.M.; Tilg, H.; Van Hul, M.; Cani, P.D. Gut Microbiome and Health: Mechanistic Insights. Gut 2022, 71, 1020–1032. [Google Scholar] [CrossRef]
- Valdes, A.M.; Louca, P.; Visconti, A.; Asnicar, F.; Bermingham, K.; Nogal, A.; Wong, K.; Michelotti, G.A.; Wolf, J.; Segata, N.; et al. Vitamin A Carotenoids, but Not Retinoids, Mediate the Impact of a Healthy Diet on Gut Microbial Diversity. BMC Med. 2024, 22, 321. [Google Scholar] [CrossRef]
- Menni, C.; Zhu, J.; Le Roy, C.I.; Mompeo, O.; Young, K.; Rebholz, C.M.; Selvin, E.; North, K.E.; Mohney, R.P.; Bell, J.T.; et al. Serum Metabolites Reflecting Gut Microbiome Alpha Diversity Predict Type 2 Diabetes. Gut Microbes 2020, 11, 1632–1642. [Google Scholar] [CrossRef]
- Pittayanon, R.; Lau, J.T.; Yuan, Y.; Leontiadis, G.I.; Tse, F.; Surette, M.; Moayyedi, P. Gut Microbiota in Patients with Irritable Bowel Syndrome—A Systematic Review. Gastroenterology 2019, 157, 97–108. [Google Scholar] [CrossRef]
- Kraenzlin, M.E.; Seibel, M.J. Measurement of Biochemical Markers of Bone Resorption. In Dynamics of Bone and Cartilage Metabolism: Principles and Clinical Applications; Academic Press: Cambridge, MA, USA, 2006; pp. 541–563. [Google Scholar] [CrossRef]
- Kang, W.; Choi, D.; Son, B.; Park, S.; Park, T. Activation of OR10A3 by Suberic Acid Promotes Collagen Synthesis in UVB-Irradiated Dermal Fibroblasts via the CAMP-Akt Pathway. Cells 2022, 11, 3961. [Google Scholar] [CrossRef]
- Long, K.; Gong, A.; Zheng, T.; Liu, S.; Ying, Z.; Xiao, C. The Relationship between Metabolite Mediated Immune Regulatory Imbalance and the Occurrence of Malignant Tumors of Bone and Articular Cartilage: A Mendelian Randomization Study. Front. Immunol. 2024, 15, 1433219. [Google Scholar] [CrossRef]
- Chen, M.; Ruan, G.; Chen, L.; Ying, S.; Li, G.; Xu, F.; Xiao, Z.; Tian, Y.; Lv, L.; Ping, Y.; et al. Neurotransmitter and Intestinal Interactions: Focus on the Microbiota-Gut-Brain Axis in Irritable Bowel Syndrome. Front. Endocrinol. 2022, 13, 817100. [Google Scholar] [CrossRef]
- Antonioli, L.; Fornai, M.; Colucci, R.; Ghisu, N.; Tuccori, M.; Del Tacca, M.; Blandizzi, C. Regulation of Enteric Functions by Adenosine: Pathophysiological and Pharmacological Implications. Pharmacol. Ther. 2008, 120, 233–253. [Google Scholar] [CrossRef] [PubMed]
- So, S.Y.; Savidge, T.C. Sex-Bias in Irritable Bowel Syndrome: Linking Steroids to the Gut-Brain Axis. Front. Endocrinol. 2021, 12, 684096. [Google Scholar] [CrossRef] [PubMed]
- Mulak, A.; Taché, Y.; Larauche, M. Sex Hormones in the Modulation of Irritable Bowel Syndrome. World J. Gastroenterol. WJG 2014, 20, 2433. [Google Scholar] [CrossRef] [PubMed]
- Nozu, T.; Miyagishi, S.; Nozu, R.; Takakusaki, K.; Okumura, T. Dehydroepiandrosterone Sulfate Improves Visceral Sensation and Gut Barrier in a Rat Model of Irritable Bowel Syndrome. Eur. J. Pharmacol. 2019, 852, 198–206. [Google Scholar] [CrossRef]
- Livshits, G.; Macgregor, A.J.; Gieger, C.; Malkin, I.; Moayyeri, A.; Grallert, H.; Emeny, R.T.; Spector, T.; Kastenmuller, G.; Williams, F.M.K. An Omics Investigation into Chronic Widespread Musculoskeletal Pain Reveals Epiandrosterone Sulfate as a Potential Biomarker. Pain 2015, 156, 1845. [Google Scholar] [CrossRef]
- Vehof, J.; Zavos, H.M.S.; Lachance, G.; Hammond, C.J.; Williams, F.M.K. Shared Genetic Factors Underlie Chronic Pain Syndromes. Pain 2014, 155, 1562–1568. [Google Scholar] [CrossRef]
- Gudin, J.A.; Laitman, A.; Nalamachu, S. Opioid Related Endocrinopathy. Pain Med. 2015, 16, S9–S15. [Google Scholar] [CrossRef]
- Talley, J.T.; Mohiuddin, S.S. Biochemistry, Fatty Acid Oxidation; StatPearls: Tampa, FL, USA, 2023. [Google Scholar]
- Karpe, A.V.; Liu, J.W.; Shah, A.; Koloski, N.; Holtmann, G.; Beale, D.J. Utilising Lipid and, Arginine and Proline Metabolism in Blood Plasma to Differentiate the Biochemical Expression in Functional Dyspepsia (FD) and Irritable Bowel Syndrome (IBS). Metabolomics 2022, 18, 38. [Google Scholar] [CrossRef]
- Zhang, C.Y.; Yao, X.; Sun, G.; Yang, Y.S. Close Association between Abnormal Expressed Enzymes of Energy Metabolism and Diarrhea-Predominant Irritable Bowel Syndrome. Chin. Med. J. 2019, 132, 135–144. [Google Scholar] [CrossRef]
- Dai, X.; Liang, M.; Dai, Y.; Ding, S.; Sun, X.; Xu, L. Causality of Genetically Determined Blood Metabolites on Irritable Bowel Syndrome: A Mendelian Randomization Study. PLoS ONE 2024, 19, e0298963. [Google Scholar] [CrossRef]
- Clarke, G.; Fitzgerald, P.; Hennessy, A.A.; Cassidy, E.M.; Quigley, E.M.M.; Ross, P.; Stanton, C.; Cryan, J.F.; Dinan, T.G. Marked Elevations in Pro-Inflammatory Polyunsaturated Fatty Acid Metabolites in Females with Irritable Bowel Syndrome. J. Lipid Res. 2010, 51, 1186. [Google Scholar] [CrossRef]
- Zhu, H.; Zhang, Y.; Du, S.; Wang, H.; Zheng, Y. Colonic Mucosal Biopsy Location Can Not Affect the Results of Mucosal Metabolomics and Mucosal Microbiota Analysis in IBS. Front. Med. 2023, 10, 1183484. [Google Scholar] [CrossRef]
- Ju, X.; Jiang, Z.; Ma, J.; Yang, D. Changes in Fecal Short-Chain Fatty Acids in IBS Patients and Effects of Different Interventions: A Systematic Review and Meta-Analysis. Nutrients 2024, 16, 1727. [Google Scholar] [CrossRef]
- Brierley, S.M.; Greenwood-Van Meerveld, B.; Sarnelli, G.; Sharkey, K.A.; Storr, M.; Tack, J. Targeting the Endocannabinoid System for the Treatment of Abdominal Pain in Irritable Bowel Syndrome. Nat. Rev. Gastroenterol. Hepatol. 2023, 20, 5–25. [Google Scholar] [CrossRef]
- Creeden, J.F.; Gordon, D.M.; Stec, D.E.; Hinds, T.D. Bilirubin as a Metabolic Hormone: The Physiological Relevance of Low Levels. Am. J. Physiol. Endocrinol. Metab. 2021, 320, E191–E207. [Google Scholar] [CrossRef]
- Balmus, I.M.; Ciobica, A.; Cojocariu, R.; Luca, A.C.; Gorgan, L. Irritable Bowel Syndrome and Neurological Deficiencies: Is There A Relationship? The Possible Relevance of the Oxidative Stress Status. Medicina 2020, 56, 175. [Google Scholar] [CrossRef]
- Martínez, A.; Barbosa, A. Are Pterins Able to Modulate Oxidative Stress? Theor. Chem. Acc. 2010, 127, 485–492. [Google Scholar] [CrossRef]
- Ghosh, S.; Whitley, C.S.; Haribabu, B.; Jala, V.R. Regulation of Intestinal Barrier Function by Microbial Metabolites. Cell. Mol. Gastroenterol. Hepatol. 2021, 11, 1463–1482. [Google Scholar] [CrossRef]
- Ng, Q.X.; Soh, A.Y.S.; Loke, W.; Lim, D.Y.; Yeo, W.S. The Role of Inflammation in Irritable Bowel Syndrome (IBS). J. Inflamm. Res. 2018, 11, 345–349. [Google Scholar] [CrossRef]
- Aziz, I.; Törnblom, H.; Palsson, O.S.; Whitehead, W.E.; Simrén, M. How the Change in IBS Criteria From Rome III to Rome IV Impacts on Clinical Characteristics and Key Pathophysiological Factors. Am. J. Gastroenterol. 2018, 113, 1017–1025. [Google Scholar] [CrossRef]
- Sumner, L.W.; Amberg, A.; Barrett, D.; Beale, M.H.; Beger, R.; Daykin, C.A.; Fan, T.W.M.; Fiehn, O.; Goodacre, R.; Griffin, J.L.; et al. Proposed Minimum Reporting Standards for Chemical Analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI). Metabolomics 2007, 3, 211–221. [Google Scholar] [CrossRef] [PubMed]
- Schymanski, E.L.; Jeon, J.; Gulde, R.; Fenner, K.; Ruff, M.; Singer, H.P.; Hollender, J. Identifying Small Molecules via High Resolution Mass Spectrometry: Communicating Confidence. Environ. Sci. Technol. 2014, 48, 2097–2098. [Google Scholar] [CrossRef] [PubMed]
Urine (n = 1526) | Serum (n = 1939) | Stool (n = 1470) | ||||
---|---|---|---|---|---|---|
IBS Cases | Controls | IBS Cases | Controls | IBS Cases | Controls | |
N | 185 | 1341 | 232 | 1707 | 186 | 1284 |
N females (%) | 169 (91.35%) | 1144 (85.31%) | 212 (91.38%) | 1494 (87.52%) | 167 (89.78%) | 1087 (84.66%) |
IBS-C, n (%) | 57(3.74%) | 69 (3.65%) | 59 (4.01%) | |||
IBS-D, n (%) | 113 (7.40%) | 137 (7.07%) | 108 (7.35%) | |||
IBS-M, n (%) | 15 (0.98%) | 26 (1.34%) | 19 (1.30%) | |||
IBD, n (%) | 11 (5.95%) | 16 (1.19%) | 15 (6.47%) | 20 (1.16%) | 10 (5.38%) | 17 (1.32%) |
Age, years mean (SD) | 61.52 (11.77) | 61.00 (13.19) | 62.88 (12.22) | 63.39 (12.35) | 62.23 (12.56) | 62.77 (12.98) |
BMI, kg/m2 mean (SD) | 26.60 (5.11) | 26.01 (4.96) | 26.59 (5.01) | 25.98 (4.89) | 26.31 (4.66) | 25.89 (4.84) |
Anti-depressants and anxiolytics n (%) | 35 (18.92%) | 105 (7.83%) | 41 (17.67%) | 150 (8.79%) | 35 (18.82%) | 109 (8.49%) |
Laxatives | 12 (6.49%) | 21 (1.57%) | 14 (6.03%) | 20 (1.17%) | 12 (6.45%) | 20 (1.56%) |
Antispasmodics and antimotility n (%) | 13 (7.03%) | 10 (0.75%) | 17 (7.33%) | 15 (0.88%) | 13 (6.99%) | 11 (0.86%) |
Analgesics, n (%) | 25 (13.51%) | 80 (5.97%) | 36 (15.52%) | 112 (6.56%) | 27 (14.52%) | 85 (6.62%) |
Healthy Eating Index | 59.23 (11.23) | 60.02 (9.72) | 59.15 (10.96) | 60.34 (9.79) | 58.94 (10.8) | 60.12 (9.65) |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kirk, D.; Louca, P.; Attaye, I.; Zhang, X.; Wong, K.E.; Michelotti, G.A.; Falchi, M.; Valdes, A.M.; Williams, F.M.K.; Menni, C. Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome. Metabolites 2025, 15, 121. https://doi.org/10.3390/metabo15020121
Kirk D, Louca P, Attaye I, Zhang X, Wong KE, Michelotti GA, Falchi M, Valdes AM, Williams FMK, Menni C. Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome. Metabolites. 2025; 15(2):121. https://doi.org/10.3390/metabo15020121
Chicago/Turabian StyleKirk, Daniel, Panayiotis Louca, Ilias Attaye, Xinyuan Zhang, Kari E. Wong, Gregory A. Michelotti, Mario Falchi, Ana M. Valdes, Frances M. K. Williams, and Cristina Menni. 2025. "Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome" Metabolites 15, no. 2: 121. https://doi.org/10.3390/metabo15020121
APA StyleKirk, D., Louca, P., Attaye, I., Zhang, X., Wong, K. E., Michelotti, G. A., Falchi, M., Valdes, A. M., Williams, F. M. K., & Menni, C. (2025). Multifluid Metabolomics Identifies Novel Biomarkers for Irritable Bowel Syndrome. Metabolites, 15(2), 121. https://doi.org/10.3390/metabo15020121