SAN ANTONIO — Oral supplementation with 2 unique forms of human milk oligosaccharides (HMOs) can provide nutritional support that significantly reduces abnormal stool consistency and abdominal pain and bloating, and improves health-related quality of life in patients with irritable bowel syndrome (IBS) of all subtypes, according to research presented at a plenary session of the American College of Gastroenterology Annual Scientific Meeting, held October 25 to 30, 2019, in San Antonio, Texas.

The nationwide study enrolled 317 subjects (70.7% women; mean age 44.0 years) across 17 sites. The participants were given 5 g orally of the HMOs 2’fucosyllactose (2’FL) and lacto-Nneotetraose (LNnT) in a 4:1 mix daily for 12 weeks. IBS symptoms, bowel habits, and quality of life were monitored at baseline and every 4 weeks during the study. Results were evaluated with intention-to-treat methodology, using repeated measures analysis of variance.

The findings demonstrated that oral supplementation with 2’FL and LNnT led to a significant improvement in overall symptoms (fecal consistency, abdominal pain, and bloating) as well as improved quality of life as measured by the IBS Severity Scoring System. Furthermore, younger age was predictive of greater improvement in stool consistency and reduction in abdominal pain severity.

Gastroenterology Advisor spoke to Magnus Simrén, MD, PhD, about his work on HMOs and how they have been shown to significantly improve IBS symptoms. He also discussed the growing acceptance in the medical community of microbiota-directed therapies, such as the inclusion of prebiotic HMOs in IBS dietary planning.

Gastroenterology Advisor (GA): Numerous pathophysiologic mechanisms have been explored in IBS, and its phenotype is markedly heterogeneous. Because of this, it is widely acknowledged that diagnosis relies largely on the absence of any specific or unique organic pathology, such as in IBD or celiac disease. What recent developments in microbiota research do you believe will challenge this assumption?

Dr Simrén: When it comes to pathophysiology of IBS, the role of microbiota has been acknowledged substantially in the last 2 years. We now know that patients with IBS have abnormal gut microbiota function and/or composition of microbiota. But we still have much to learn regarding its role as a biomarker and its relevance for symptom generation. There are some biomarkers for IBS that are under investigation currently, but the results of these studies are mostly relevant to predicting treatment response rather than as diagnostic tools. Even though there has been substantial progress in this field recently, more studies are certainly needed.

GA: Is there a growing acceptance in the medical community for recommending microbiota-directed therapies? Why do you believe that prebiotics will become as popular as probiotics for improving gut health?

Dr Simrén: Generally, there is a growing acceptance in the medical community for recommending microbiota-directed therapies. We now know that prebiotics can stimulate the abundance of good bacteria, thereby improving microbiota composition and function. One study demonstrated that effects of a prebiotic were comparable to the effect of a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyols diet. There is also wide acceptance for therapies that are natural, especially those that come from human milk. If we follow the adoption path for probiotics — it began with studies that demonstrated promising results and positive effects — there is potential for prebiotics to become as widely adopted as probiotics.

GA: What are the current challenges in restoring intestinal microbiota composition and functioning?

Dr Simrén: I believe the biggest challenge we have is that we do not yet understand the complexity of the microbiota and how the composition and function should be to have an optimal gut health profile. There are thousands of different bacteria in the gut and we have yet to understand the optimum balance needed for optimal gut function.

GA: Why are HMOs a promising approach to address altered microbiota to improve gut-barrier function? Can you tell us briefly about your research findings and their clinical significance?

Dr Simrén: We have executed proof-of-concept studies in smaller groups of patients and healthy volunteers in which we have demonstrated that HMOs can stimulate good bacteria in the gut. As a follow-up, the current open-label trial tracked the responses of 317 enrolled patients with IBS for 12 weeks. The 2 unique combinations of HMOs show they can stabilize bowel function and reduce the severity of IBS symptoms, such as abdominal pain and abdominal bloating. Those who followed the HMO treatment also reported improved quality of life. The study results are very promising. If anything, it appears that the combination of these 2 forms of HMOs are producing better results than many other available IBS treatments.  

GA: In this trial, findings suggested that oral supplementation with a blend of 2 HMOs can provide nutritional support that significantly reduces abnormal stool consistency, abdominal pain, bloating, and improves health-related quality of life in IBS of all subtypes. What are the possible mechanisms behind symptom improvement?

Dr Simrén: This trial didn’t address the possible mechanisms behind symptom improvement. The hypothesis we focused on is that if we can increase good bacteria in the gut, we can promote better gut health and improve gut function. To prove this, we will need to develop another study that can look at the relationship between symptom improvement and the potential mechanism of action.

GA: More than 70% of those who received the combination of 2 HMOs to support bowel habits, improve other bowel symptoms, and improve quality of life of patients with IBS were women. Do you believe the findings are similarly applicable to both men and women? What were the demographics of this study, and are there any groups of patients in whom this therapy might be contraindicated? What are the most common adverse events related to this approach?

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Dr Simrén: The symptom improvement was similar regardless of sex. However, we did notice that the clinical response seemed to be somewhat better in younger patients. There have been no studies in pregnant or breastfeeding women, and there are no theoretic concerns since the HMOs are present in human milk. In addition, only a very small percentage of patients — 8 of the 317 enrolled — reported side effects that were severe enough to stop the treatment prematurely. The therapy was very well tolerated. Those who reported adverse events indicated they were very mild and did not lead to discontinuation of therapy or drop out of the trial.

GA: Do you believe that HMO therapy will have similar safety and efficacy for pediatric IBS?

Dr Simrén: There are very few studies on microbiota alteration in pediatric patients with IBS, but existing studies demonstrate findings similar to those in adults. To the best of my knowledge there hasn’t been any current research exploring the use of prebiotics in pediatric IBS. However, it’s quite likely this unique HMO combination will also be effective in pediatric patients.

GA: What are some future studies you would like to pursue?

Dr Simrén: Now that we have completed this open-label trial with positive results, I believe the next step is to execute a study comparing the HMOs with a placebo and also to incorporate how changes in the gut function can be correlated with symptom improvement to better understand the mechanism of action.

Reference

Simrén M, Peery A, Seitzberg D, Amundsen ID, McConnell B, Palsson OS. Human milk oligosaccharides improve all the central symptoms of irritable bowel syndrome: a multi-center, open label trial. Presented at: ACG Annual Scientific Meeting; October 25-30, 2019; San Antonio, TX. Abstract 43.