Human Milk Oligosaccharides Support Normal Bowel Function and Improve Symptoms of Irritable Bowel Syndrome: A Multicenter, Open-Label Trial

Olafur S Palsson, Anne Peery, Dorthe Seitzberg, Ingvild Dybdrodt Amundsen, Bruce McConnell, Magnus Simrén, Olafur S Palsson, Anne Peery, Dorthe Seitzberg, Ingvild Dybdrodt Amundsen, Bruce McConnell, Magnus Simrén

Abstract

Introduction: Treatment options for irritable bowel syndrome (IBS) are limited, causing many patients to remain symptomatic. This study assessed the potential of human milk oligosaccharides (HMOs) to normalize bowel habits. Secondary outcomes included IBS severity and health-related quality of life.

Methods: This multicenter, open-label trial recruited patients with IBS from 17 sites across the United States. Patients received daily orally administrated 5-g intervention of the HMOs 2'-fucosyllactose and lacto-N-neotetraose in a 4:1 mix. Bowel habits, IBS symptoms, and quality of life were assessed at baseline and every 4 weeks during the 12-week intervention.

Results: A total of 317 patients (70.7% women; mean age of 44.0 years, range 18-93 years) received the trial product, and 245 patients completed the trial according to protocol. Patients had a significant improvement from baseline to 12 weeks in total percentage of bowel movements with abnormal stool consistency (mean and [95% confidence interval]: 90.7 [88.9-92.9] vs 57.2% [53.9-60.5], P < 0.0001), overall IBS Symptom Severity Score (323 [314-332] vs 144 [133-155], P < 0.0001) and health-rela,ted quality of life (50.4 [48.0-52.8] vs 74.6 [72.3-76.9], P < 0.0001). Improvement was similar across IBS subtypes. Symptoms improved most in the first 4 weeks of intervention. The most common side effects were mild gastrointestinal symptoms such as flatulence, abdominal pain and discomfort, and distension.

Discussion: Supplementation with 2 selected HMOs improves IBS symptoms and quality of life without substantial side effects. These promising results suggest that this novel approach to IBS should be confirmed in a randomized, placebo-controlled trial.

Trial registration: ClinicalTrials.gov NCT03550742.

Conflict of interest statement

Guarantor of the article: Olafur S. Palsson, PsyD.

Specific author contributions: O.S.P., M.S., and B.M.: contributed in designing the trial. O.S.P.: responsible for data collection and database cleaning and analyzed the data. O.P. and I.D.A.: prepared the manuscript. All authors had full access to the study data, had input to the content of the manuscript, contributed in finalizing the manuscript, and approved the final version for submission.

Financial support: The trial was sponsored by Glycom, Inc., LA. The trial sponsor was involved in designing the trial and writing of the manuscript.

Potential competing interests: O. S. Palsson has received research support from Glycom and the Rome Foundation and served as Consultant/Advisory Board Member for Ironwood and metaMe Health. A. Peery declares no conflict of interest. D. Seitzberg, I. D. Amundsen, and B. McConnell are employed at Glycom A/S, Denmark. M. Simrén has received unrestricted research grants from Danone and Ferring Pharmaceuticals and served as a Consultant/Advisory Board member for AstraZeneca, Danone Nutricia Research, Nestlé, Almirall, Allergan, Albireo, Genetic Analysis AS, Biocodex, Glycom, Arena, and Shire and as a speaker for Tillotts, Takeda, Menarini, Kyowa Kirin, Allergan, Shire, Biocodex, Alimentary Health, AlfaSigma, and Almirall.

ClinicalTrials.gov identifier: NCT03550742.

Figures

Figure 1.
Figure 1.
Patient flow. ITT, intention-to-treat; PP, per protocol.
Figure 2.
Figure 2.
Changes in total % of abnormal consistency stools (Bristol Stool Form Scale) during 12 weeks of daily supplementation of a 5-g mix of 2'-fucosyllactose and lacto-N-neotetraose. *Significantly reduced total % of abnormal stools (diarrhea + constipation) compared with baseline at P < 0.0001.
Figure 3.
Figure 3.
Changes in the overall IBS Symptom Severity Score during 12 weeks of daily supplementation with a 5-g mix of 2'-fucosyllactose and lacto-N-neotetraose in the different IBS subtypes. *Significantly different from baseline at P < 0.0001. Error bars: 95% confidence interval. IBS, irritable bowel syndrome; IBS-C, constipation-predominant IBS; IBS-D, diarrhea-predominant IBS; IBS-M, alternating/mixed-pattern IBS.
Figure 4.
Figure 4.
Changes in (a) abdominal pain severity (0–100 scale), (b) number of days with abdominal pain (out of 10 days), and (c) bloating severity (0–100 scale) during 12 weeks of daily supplementation with a 5-g mix of 2'-fucosyllactose and lacto-N-neotetraose in the different IBS subtypes. All subtypes and the overall sample were significantly improved on all these parameters at 12 weeks. *Significantly different from baseline at P < 0.0001. Error bars: 95% confidence interval. IBS, irritable bowel syndrome; IBS-C, constipation-predominant IBS; IBS-D, diarrhea-predominant IBS; IBS-M, alternating/mixed-pattern IBS.

References

    1. Ford AC, Talley NJ. Irritable bowel syndrome. BMJ 2012;345:e5836.
    1. Spinelli A. Irritable bowel syndrome. Clin Drug Investig 2007;27(1):15–33.
    1. Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology 2006;130(5):1480–91.
    1. Lovell RM, Ford AC. Global prevalence of and risk factors for irritable bowel syndrome: A meta-analysis. Clin Gastroenterol Hepatol 2012;10(7):712–21.e4.
    1. Palsson OS, Whitehead W, Törnblom H, et al. Prevalence of Rome IV functional bowel disorders among adults in the United States, Canada, and the United Kingdom. Gastroenterology 2020;158(5):1262–73.e3.
    1. Canavan C, West J, Card T. The epidemiology of irritable bowel syndrome. Clin Epidemiol 2014;6:71–80.
    1. Choung RS, Locke GR., III Epidemiology of IBS. Gastroenterol Clin North Am 2011;40(1):1–10.
    1. Lea R, Whorwell PJ. Quality of life in irritable bowel syndrome. Pharmacoeconomics 2001;19(6):643–53.
    1. Lovell RM, Ford AC. Effect of gender on prevalence of irritable bowel syndrome in the community: Systematic review and meta-analysis. Am J Gastroenterol 2012;107(7):991–1000.
    1. Camilleri M, Ford AC. Pharmacotherapy for irritable bowel syndrome. J Clin Med 2017;6(11):101.
    1. 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.
    1. Thabane M, Simunovic M, Akhtar-Danesh N, et al. An outbreak of acute bacterial gastroenteritis is associated with an increased incidence of irritable bowel syndrome in children. Am J Gastroenterol 2010;105(4):933–9.
    1. Casen C, Vebø H, Sekelja M, et al. Deviations in human gut microbiota: A novel diagnostic test for determining dysbiosis in patients with IBS or IBD. Aliment Pharmacol Ther 2015;42(1):71–83.
    1. Jeffery IB, O'Toole PW, Öhman L, et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut 2012;61(7):997–1006.
    1. Pittayanon R, Lau JT, Yuan Y, et al. Gut microbiota in patients with irritable bowel syndrome—A systematic review. Gastroenterology 2019;157(1):97–108.
    1. Whorwell PJ, Altringer L, Morel J, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol 2006;101(7):1581–90.
    1. Vigsnæs LK, Salomonsson E, McConnell B. Human milk oligosaccharides; now as powerful, specific modulators of the adult gut microbial community. The 11th Vahouny Fiber Symposium, 2017. June 15, 2017, Bethesda, MD.
    1. 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.
    1. Turroni F, Peano C, Pass DA, et al. Diversity of bifidobacteria within the infant gut microbiota. PLoS One 2012;7(5):e36957.
    1. Bode L. Human milk oligosaccharides: Every baby needs a sugar mama. Glycobiology 2012;22(9):1147–62.
    1. Brand-Miller JC, McVeagh P, McNeil Y, et al. Digestion of human milk oligosaccharides by healthy infants evaluated by the lactulose hydrogen breath test. J Pediatr 1998;133(1):95–8.
    1. Engfer MB, Stahl B, Finke B, et al. Human milk oligosaccharides are resistant to enzymatic hydrolysis in the upper gastrointestinal tract. Am J Clin Nutr 2000;71(6):1589–96.
    1. Gnoth MJ, Kunz C, Kinne-Saffran E, et al. Human milk oligosaccharides are minimally digested in vitro. J Nutr 2000;130(12):3014–20.
    1. Bode L. The functional biology of human milk oligosaccharides. Early Hum Dev 2015;91(11):619–22.
    1. 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.
    1. Iribarren C, Törnblom 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.
    1. World Medical Association. World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA 2013;310(20):2191–4.
    1. Lewis S, Heaton K. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol 1997;32(9):920–4.
    1. Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: A simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther 1997;11(2):395–402.
    1. Dimenäs E, Glise H, Hallerbäck B, et al. Well-being and gastrointestinal symptoms among patients referred to endoscopy owing to suspected duodenal ulcer. Scand J Gastroenterol 1995;30(11):1046–52.
    1. Patrick DL, Drossman DA, Frederick IO, et al. Quality of life in persons with irritable bowel syndrome (development and validation of a new measure). Dig Dis Sci 1998;43(2):400–11.
    1. Lacy BE, Mearin F, Chang L, et al. Bowel disorders. Gastroenterology 2016;150(6):1393–407.e5.
    1. Iribarren C, Magnusson MK, Törnblom H, et al. Efficacy of human milk oligosaccharides on fecal microbiota in patients with IBS. Gastroenterology 2019;156(6):S-2–35..
    1. Steenhout P, Sperisen P, Martin FP, et al. Term infant formula supplemented with human milk oligosaccharides (2′ fucosyllactose and lacto-N-neo tetraose) shifts stool microbiota and metabolic signatures closer to that of breastfed infants. FASEB J 2016;30(1_Suppl):275–7.
    1. Elison E, Vigsnaes LK, Rindom Krogsgaard L, et al. Oral supplementation of healthy adults with 2'-O-fucosyllactose and lacto-N-neotetraose is well tolerated and shifts the intestinal microbiota. Br J Nutr 2016;116(8):1356–68.
    1. O'Callaghan A, van Sinderen D. Bifidobacteria and their role as members of the human gut microbiota. Front Microbiol 2016;7:925.
    1. 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.
    1. Staudacher HM, Whelan K. Altered gastrointestinal microbiota in irritable bowel syndrome and its modification by diet: Probiotics, prebiotics and the low FODMAP diet. Proc Nut Soc 2016;75(3):306–18.
    1. Powell N, Walker MM, Talley NJ. Gastrointestinal eosinophils in health, disease and functional disorders. Nat Rev Gastroenterol Hepatol 2010;7(3):146–56.
    1. Shulman RJ, Eakin MN, Czyzewski DI, et al. Increased gastrointestinal permeability and gut inflammation in children with functional abdominal pain and irritable bowel syndrome. J Pediatr 2008;153(5):646–50.
    1. Drossman DA, Camilleri M, Mayer EA, et al. AGA technical review on irritable bowel syndrome. Gastroenterology 2002;123(6):2108–31.
    1. Bienenstock J, Buck RH, Linke H, et al. Fucosylated but not sialylated milk oligosaccharides diminish colon motor contractions. PLoS One 2013;8(10):e76236.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться