Abstract/Summary

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction that substantially impairs quality of life yet lacks consistently effective treatments. The gut microbiota has emerged as a potential therapeutic target, and human milk oligosaccharides (HMOs) are promising candidates due to their selective stimulation of bifidobacteria and capacity to modulate microbial metabolism, acting as prebiotics. This thesis evaluated the potential of HMOs as a gut microbiota-directed intervention for IBS through four complementary studies. A narrative review established the conceptual rationale. In vitro batch cultures compared healthy vs IBS stool fermentations, confirming HMO enhancement of beneficial taxa, such as Bifidobacterium, and short-chain fatty acids. Focus groups with patients highlighted acceptability and practical considerations for daily use. Finally, a randomised, placebo-controlled crossover trial tested an HMO blend in adults with IBS. While the intervention did not improve symptoms beyond placebo, it consistently modulated the gut microbiota and metabolome and was well tolerated. Collectively, these findings show that HMOs are biologically active and acceptable in adults with IBS, providing a mechanistic and patient-centred foundation for longer, stratified clinical studies.