The role of volatile organic compounds in the diagnosis and treatment of irritable bowel syndrome.

Conley, Thomas ORCID: 0000-0002-0604-0770 (2025) The role of volatile organic compounds in the diagnosis and treatment of irritable bowel syndrome. PhD thesis, University of Liverpool.

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Abstract

Irritable bowel syndrome (IBS) is a prevalent and burdensome disorder of gut–brain interaction, defined by intrusive abdominal pain and disordered bowel habits. It affects a significant proportion of the global population and contributes substantially to healthcare expenditure in the United Kingdom. Despite its impact, the pathophysiology of IBS remains poorly understood, and treatment remains largely symptom-based, lacking alignment with clearly defined biological mechanisms. This unmet need has made understanding the drivers of IBS symptoms a top research priority. The gut microbiota has long been implicated in IBS, yet consistent microbial signatures remain elusive. Whilst advances in sequencing have enabled detailed analysis of microbial composition, these methods are expensive, technically complex, and often fail to infer functionality. Crucially, large shifts in community composition do not necessarily reflect functional change, and the most metabolically active organisms may paradoxically be those present in the lowest abundance. In this context, metabolomic approaches - particularly volatile organic compound (VOC) analysis - offer a promising, rapid, scalable, and cost-effective means to gain functional insight into the gut microenvironment, capturing end-products of microbial (and host) metabolism. Indeed, early evidence suggests that VOC profiles can not only distinguish IBS from other gastrointestinal disorders but may also help predict responsiveness to dietary interventions. Solid-phase microextraction gas chromatography–mass spectrometry (SPME-GC-MS) was employed to profile VOCs emitted into the faecal headspace of well-phenotyped individuals with IBS. The application of both unsupervised and supervised clustering methods enabled the stratification of patients based on metabolic profiles. This revealed two robust and reproducible metabotypes, including a metabolically agile group characterised by a relative abundance of short-chain fatty acids (SCFAs), associating with a specific microbial signature, more severe clinical features and enhanced clinical response to the restriction of FODMAPs (fermentable oligosaccharides, disachharides, monosachharides and polyols). A statistical model can be built around these metabotypes, enabling the prediction of microbial signature at baseline using just five VOCs. Complementary analysis of urine via derivatized GC-MS further enriched insights into the relationship between faecal metabolites and more complex downstream mediators, demonstrating strong correlations between faecal SCFAs and urinary markers of tryptophan metabolism, suggesting a possible SCFA-serotonin axis in IBS. Compellingly, stark differences in the baseline urinary metabotypes of responders and non-responders to FODMAP restriction suggest, for the first time, a feasible and acceptable non-invasive tool for pre-treatment stratification. Collectively, these findings enhance our understanding of IBS pathophysiology and support the integration of metabolomic stratification into clinical care - bringing precision, biologically grounded IBS care closer to clinical reality.

Item Type:	Thesis (PhD)
Uncontrolled Keywords:	Irritable bowel syndrome, Volatile organic compounds, Gut metabolome, Metabotype, Short chain fatty acids
Divisions:	Faculty of Health & Life Sciences
Depositing User:	Symplectic Admin
Date Deposited:	11 Feb 2026 09:45
Last Modified:	11 Feb 2026 10:24
DOI:	10.17638/03195164
Supervisors:	Probert, Chris Pritchard, Mark
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3195164
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