Human Milk Oligosaccharides Are Able to Impact the Gut Microbiota and Metabolites in Irritable Bowel Syndrome Patients

Introduction: The intestinal microbiota is an increasingly recognized factor in the pathogenesis of irritable bowel syndrome (IBS). This may be mediated through the microbiota itself or through metabolites produced by the microbiota which are key nutrients for gut barrier and immune function. Diet has a major impact on the microbiota and their metabolites and dietary interventions are increasingly used in IBS. However, the challenge is to identify dietary modifiers of the microbiota which are specific, allowing targeted intervention on the microbiota and metabolites. Human Milk Oligosaccharides (HMOs) are a family of complex carbohydrates found in human milk. In adult and infant clinical studies, HMOs specifically modulated the intestinal microbiota by increasing bifidobacteria and reducing certain detrimental bacteria. Additionally, HMOs were well tolerated. Methods: The aims of this study are to assess i) in in vitro the impact of HMOs on the microbial community and metabolites, and ii) to correlate with HMO impact on symptoms in adult IBS volunteers. In vitro gut models were used to examine the impact of HMOs on the microbiota and metabolites using faecal samples from IBS patients and healthy donors. Samples were analysed using flow cytometry coupled with fluorescent in-situ hybridization (FISH) for microbial composition and NMR spectroscopy for metabolite profiling. 45 IBS volunteers were recruited into an open label test program in which the volunteers consumed 3.5 g HMO daily for 12 weeks. Symptom scores were recorded electronically at day 0, after 3, 6, 9 and 12 weeks. Results: The studies showed (i) the microbiota of healthy and IBS patients to be different, (ii) a clear change in microbial composition and an increase in bifidobacteria in the IBS samples to levels closer to healthy, (iii) an increase in nutrient metabolites relevant to gut barrier and immune function; and (iv) a decrease in pain, dysfunctional bowel movement, bloating and certain quality of life symptoms. Conclusion: The results show that HMOs can improve the microbiota composition and metabolites of IBS patients and this dietary improvement potentially decreases IBS-like symptoms. This suggests HMOs as potential candidates for the dietary management of IBS and associated comorbidities, however clinical trials are needed to validate these results.