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Can Human Milk Oligosaccharides Improve Symptoms of Irritable Bowel Syndrome (IBS)?

August 24, 2022 7 min read

HMO clinical trial with IBS Patients

Human milk oligosaccharides (HMOs), found in breast milk, could be looked upon as a protective shield provided by mother to baby as each of us enters and develops in this world. A shield to provide defence and a comfortable and safer passage.

As science is progressing, it is uncovering more about how this group of complex glycans (complex carbohydrates), present in the milk of mammals but in higher concentrations in human breast milk, is pivotal in fighting off infection from the very beginning[i]. Further research is now becoming known about how these complex carbohydrates can maintain and even promote health.

In the 3rd article of this series, we are going to explore the potential of HMOs as a treatment for irritable bowel syndrome (IBS), focusing on a study conducted by Palsson et al.(2020)[ii].

Why was the study conducted?

The study by Palsson et al.(2020) was conducted to assess if HMOs could help improve IBS symptoms and support normal bowel function. To date, treatments for IBS, a gut-brain interaction disorder, have been limited, leaving many patients experiencing a list of sometimes severe and painful symptoms such as bloating, stomach cramps, diarrhoea, and constipation. These symptoms can last from days to weeks and can be ongoing throughout life.

So, the study by Palsson et al.(2020) could help to establish whether HMOs are an effective treatment approach for IBS, especially as there is a need for more effective strategies for patients to combat the symptoms.

Around 30% of sufferers have symptoms that are severe enough to need to see a doctor and receive medical treatment. At present, there is thought to be no known cure and the condition can impact the patient’s quality of life. Although a cure is yet to be found, dietary changes are believed to inhibit some symptoms alongside certain medicines[iii].

There is no exact known cause, but there may be some links to IBS and the following:

  • fast or slow transit of food through the gut
  • stress
  • sensitive nerves in the gut
  • family history of IBS[iv]

The potential of HMOs for the treatment of IBS

A study by Hyland et al. (2014) suggested that, although the pathogenesis (cause) of IBS is unknown, there is mounting evidence that the gut microbiota could be a contributing factor. There has been a rise in clinical trials studying the development of IBS following intestinal infection as well as the microbiota-host response in the condition and observing the changes in bacterial populations within the gut in IBS patients.

The evidence suggests that upregulation of the body’s immune defence system, coupled with changes to the bacterial populations within the gut, can aid in the fight against invading bacteria. These processes could be pivotal in promoting and sustaining immune responses extending from the host’s gut and beyond[v].

HMOs are a heterogenous mix of glycans that are highly concentrated in human breast milk. The upper gastrointestinal (GI) tract cannot digest most of the HMOs, meaning a large proportion arrive in the large intestine intact and are ready to boost your health.

HMOs are a type of prebiotic, so they help to nourish the good bacteria in your colon and have numerous roles in your gut. One of these roles is they assist in controlling the gut flora and keeping it in a healthy balance. Another is helping the immune system function and aiding in the prevention of intestinal pathogens binding to the epithelial cells [vi] [vii] [viii].

A systematic review by Pittayanon et al. (2019) found that Bifidobacteria,as well as Faecalibacterium, including F. prausnitzii and Lactobacillaceae, were depleted in IBS patients[ix]. However, Steenhout et al.(2016) showed that a supplementation mix containing the HMOs 2’fucosyllactose (2’FL) and lacto-N-neotetraose (LNnT) increased the abundance of faecal Bifidobacteria,a bacterium that is considered good, in healthy infants[x]. Therefore, HMOs could help to restore the balance within the gut of individuals with IBS.

Furthermore, a large randomized, placebo-controlled (non-treatment mix and actual treatment mix) proof of principle (experimenting with new technologies) study was conducted by Iribarren et al.(2020). The study used a supplement 4:1 mix of HMOs, 2’FL, and LNnT, respectively, and had 61 adult participants, all of which had been diagnosed with IBS. The results showed an increase in faecal Bifidobacterium abundance in participants who were given a 10g dose of 2’FL/LNnT without worsening the symptoms of IBS[xi]. The study concluded that this type of approach may be beneficial for modulating the gut microbiota of IBS patients and helping them move closer to a healthier profile.

Bifidobacteriais an important gut microbe. Not only is it one of the first colonisers of the human gut, but it also produces important metabolites, like short-chain fatty acids (SCFAs) and vitamins. One of the SCFAs Bifidobacteriaproduces is acetate[xii].

Acetate has been shown to maintain the pH in the colon as well as being a substrate used in the synthesis of butyrate, an important energy source for the good bacteria in the colon[xiii]. A study by Dunlop et al. (2006) suggested that the increase in butyrate concentrations in the colon could help to support the gut barrier, which is compromised in people with IBS[xiv].

These studies have shown that using treatments and techniques involving HMOs may help to stabilise and support normal bowel function. HMOs may also help to reduce or even eliminate symptoms of conditions such as IBS.

How was the study conducted, and what methods were used?

The study was a multicentre (study conducted at more than one site), open-label trial (trial where the treatment is known). Across the USA, 17 different sites were used, involving a total of 317 patients.

Participants were given a 5g intervention oral 4:1 daily mix of 2’FL and LNnT. The study lasted for 12 weeks, and bowel habits, symptoms, and quality of life were assessed at baseline, 4-, 8-, and 12-week interventions.

What did the results show?

Of the 317 patients, 245 completed the trial according to the study protocol.

A significant improvement in bowel movements and abdominal stool consistency was observed from baseline to 12 weeks, and there was no difference between men and women. However, there was a difference between age groups, where those under 40 years showed a greater reduction in bowel movements and abdominal stool consistency.

There was also an improvement in abdominal pain along with bloating and an overall improvement in the severity of IBS symptoms. These improvements were seen in the whole IBS and sub-groups. Sub-groups also experienced similar beneficial changes.

The quality of life of participants was assessed using an IBS severity score. Overall, it was shown that severity decreased. The greatest improvement in symptoms was shown in the first 4 weeks of the study and remained steady for the remaining 8 weeks. During the study, some gastrointestinal side effects were experienced in some participants. The most common was gas, followed by bloating and discomfort.

Overall, the study concluded that the ingestion of a 4:1 oral mix of the HMOs, 2’FL and LNnT improved abdominal pain, stool consistency, bloating, and the severity of the condition. Not only did the study demonstrate that HMOs could improve the quality of life of IBS patients, but it was the first large-scale study to show that HMO supplementation can improve IBS symptoms.

The main reasons for this appear to be the ability of these HMOs to increase the abundance of Bifidobacteria, which is depleted in IBS. This bacterium is important for maintaining gut health and for the production of important metabolites such as SCFAs, which help to nourish other beneficial microbes and strengthen the intestinal layer.

[[READ: the team of registered dietitians at Go Wellness review PureHMO®]]

Conclusion

IBS is a condition affecting the human bowel that has no identified cause or cure. The symptoms of IBS range from gas and bloating to severe abdominal pain that affects the daily lives of patients.

For the last few decades, research into this and other bowel diseases has been mounting and beginning to shine a light on an imbalance in the gut flora being a main instigator of disease. So, scientists have been looking at new ways to help restore the balance in the gut to treat colonic conditions, including the use of HMOs.

Now, with the results from intervention studies like that of Palsson et al.(2020), new treatments are looking to be more hopeful. Treatments using HMOs, specifically 2’FL and LNnT, mean that IBS patients could look towards better days where their debilitating symptoms can be controlled.

 

Written by: Leanne Edermaniger, M.Sc. Leanne is a professional science writer who specializes in human health and enjoys writing about all things related to the gut microbiome. 

References: 

[i] Bode L. Human Milk Oligosaccharides: Structure and Functions. Nestle Nutr Inst Workshop Ser. 2020;94:115-123. doi: 10.1159/000505339. Epub 2020 Mar 11. PMID: 32160614.

[ii] Palsson OS, Peery A, Seitzberg D, Amundsen ID, McConnell B, Simrén M. Human Milk Oligosaccharides Support Normal Bowel Function and Improve Symptoms of Irritable Bowel Syndrome: A Multicenter, Open-Label Trial. Clin Transl Gastroenterol. 2020 Dec;11(12):e00276. doi: 10.14309/ctg.0000000000000276. PMID: 33512807; PMCID: PMC7721220.

[iii] Canavan C, West J, Card T. The epidemiology of irritable bowel syndrome. Clin Epidemiol 2014;6:71–80.

[iv] Irritable bowel syndrome (IBS) [Internet]. nhs.uk. 2022 [cited 2022 Aug 23]. Available from: https://www.nhs.uk/conditions/irritable-bowel-syndrome-ibs/ 

[v] Hyland NP, Quigley EM, Brint E. Microbiota-host interactions in irritable bowel syndrome: Epithelial barrier, immune regulation and brain-gut interactions. World J Gastroenterol 2014;20(27):8859–66.

[vi] Bode L. Human milk oligosaccharides: Every baby needs a sugar mama. Glycobiology 2012;22(9):1147–62.

[vii] Bode L. The functional biology of human milk oligosaccharides. Early Hum Dev 2015;91(11):619–22

[viii] Bode L. Human milk oligosaccharides and their beneficial effects. In: Zibadi S, Watson RR, Preedy VR (eds). Handbook of Dietary and Nutritional Aspects of Human Breast Milk. Wageningen Academic Publishers: The Netherlands, 2013, pp 515–31.

[ix] Pittayanon R, Lau JT, Yuan Y, Leontiadis GI, Tse F, Surette M, Moayyedi P. Gut Microbiota in Patients with Irritable Bowel Syndrome-A Systematic Review. Gastroenterology. 2019 Jul;157(1):97-108. doi: 10.1053/j.gastro.2019.03.049. Epub 2019 Mar 30. PMID: 30940523.

[x] Alliet P, Puccio G, Janssens E, Cajozzo C, Corsello G, Berger B, Sperisen P, Martin F, Sprenger N, Steenhout p. Term infant formula supplemented with human milk oligosaccharides (2’fucosyllactose and lacto-neotetraose) shifts stool microbiota and metabolic signatures closer to that of breastfed infants. Journal of Pediatric Gastroenterology & Nutrition. 2016;63(1S):S55.

[xi] Iribarren C, Tornblom H, Aziz I, et al. Human milk oligosaccharide ¨ supplementation in irritable bowel syndrome patients: A parallel, randomized, double‐blind, placebo‐controlled study. Neurogastroenterol Motil 2020;32(10):e13920.

[xii] O’Callaghan A, van Sinderen D. Bifidobacteria and their role as members of the human gut microbiota. Front Microbiol 2016;7:925.

[xiii] Astbury SM, Corfe BM. Uptake and metabolism of the short-chain fatty acid butyrate, a critical review of the literature. Curr Drug Metab 2012; 13(6):815–21.

[xiv] Dunlop SP, Hebden J, Campbell E, et al. Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes. Am J Gastroenterol 2006;101(6):1288–94.


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