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Effects of Dietary Fibres on Indomethacin-Induced Intestinal Permeability in Elderly People: A Randomised Placebo Controlled Parallel Clinical Trial

| Gastroenterology
Authors:
John-Peter Ganda Mall,1 Frida Fart,1 Julia Sabet,1 Carl-Mårten Lindqvist,1 Åsa Keita,2 Robert-Jan Brummer,1 *Ida Schoultz1
Disclosure:

This study was financed by the European Commission’s seventh framework programme FibeBiotics. Bioactor (Netherlands) and Swedish Oat Fiber (Sweden) provided the study supplement arabinoxylan and oat β-glucan, respectively, but had no involvement in the design, analysis, or interpretation of the results in this study.

Acknowledgements:

Many thanks to the United European Gastroenterology (UEG) Week and the European Medical Journal for wishing to publish this abstract review. We would also like to acknowledge the FibeBiotics EU consortium and collaboration performed within this organisation, particularly Dr Ellen Kranenbarg-Stolte at Wageningen University, Wageningen, Netherlands, for her excellent work measuring the cytokines in this study. We would also like to thank Nordic Sugar (Sweden), Solactis (France), Biogaia (Sweden), Univar (Sweden), and Ingredi (Sweden) for providing us with the separate sugar probes needed for the in vivo multisugar permeability test. Finally, we would like to thank all study participants for taking part in this study.

Citation
EMJ Gastroenterol. ;7[1]:68-70. Abstract Review No. AR1.

Each article is made available under the terms of the Creative Commons Attribution-Non Commercial 4.0 License.

INTRODUCTION

The global population of elderly (>65 years) people is increasing and will have a major impact on healthcare systems1,2 due to an increase in age-related diseases. Gastrointestinal (GI) symptoms are common among the elderly and the elevated pharmaceutical load in elderly patients is of potential harm to the intestine. It is known that long-term use of non-steroid anti-inflammatory drugs, commonly used for pain management among the elderly, can cause gastric ulceration, enteropathy,3,4 and increased intestinal permeability.5 A deteriorated barrier function is associated with increased psychological distress in the elderly with GI symptoms,6 and we have previously shown that specific dietary fibres can attenuate stress-induced hyperpermeability ex vivo in elderly patients with GI symptoms7 and patients with Crohn’s disease.8 However, the potential of dietary fibres to strengthen the intestinal barrier function in vivo in elderly individuals is, to our knowledge, not known.

AIM

We performed a randomised, double-blind, placebo-controlled parallel clinical trial to investigate whether 6 weeks of oral supplementation of wheat-derived arabinoxylan or oat β-glucan could strengthen the gut barrier function in elderly individuals and reduce indomethacin (a non-steroidal anti-inflammatory drug)-induced gut permeability. Furthermore, changes in gut microbiota composition, inflammatory/oxidative status, and self-reported health were evaluated after intervention.

METHODS

All qualified subjects (n=49) participated in a three-arm study design. Each arm consisted of 6 weeks of intervention with arabinoxylan, oat β-glucan, or placebo (maltodextrin). The primary outcome was set to changes in indomethacin-induced intestinal permeability before and after intervention as assessed by an in vivo multisugar test. Secondary outcomes were set to changes in microbiota composition, systemic inflammatory/oxidative status, and self-reported health. Blood and faecal samples were collected at both the beginning and end of the study. Dietary intake was estimated using a food frequency questionnaire.

RESULTS

Indomethacin was found to significantly increase small intestinal permeability in all three intervention arms, while colonic permeability was significantly increased in only one of the intervention arms. No significant effects on the primary parameters (intestinal permeability) or secondary parameters (microbiota, inflammatory/oxidative levels and self-reported health) were observed after intervention with either dietary fibre compared to placebo. Food frequency questionnaire analysis revealed that 85% of all elderly participants had an insufficient fibre intake, accounting only for a median of 64.6% (IQR 50.6–83.8%) of the Nordic Nutrition Recommendations.

CONCLUSION

Our data show that supplementation of arabinoxylan or oat β-glucan was not able to attenuate indomethacin-induced intestinal permeability. However, our results show that dietary fibre intake among the elderly was below the Nordic Nutrition Recommendations levels. This emphasises the importance to further investigate the effect of dietary fibres on gut health and barrier function in elderly for the development of appropriate dietary guidelines regarding supplementation of dietary fibres.

DISCUSSION AFTER PRESENTATION

Many relevant questions were raised and discussed after the presentation. Particularly, questions regarding how the oral supplements were delivered and ingested and concerns about the impact of the food matrix that the supplements were mixed with were addressed. The supplements were delivered in powder form and were either sprinkled over breakfast or taken in a morning drink. This led to further discussion about the compliance of the study participants, which was verified by counting the remaining study products returned after the study. The discussion was very meaningful and contributed to the possible explanations of the results and their implications, which will be very useful when finalising the authors’ research manuscript.

References
Cohen JE. Human population: The next half century. Science. 2003;302(5648):1172-5. Dennison C et al. The health-related quality of life and economic burden of constipation. Pharmacoeconomics. 2005;23(5):461-76. Lagerin A et al. Extent and quality of drug use in community-dwelling people aged ≥75 years: A Swedish nationwide register-based study. Scand J Public Health. 2017. [Epub ahead of print]. Bjarnason I et al. Effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine. Gut. 1986;27(11):1292-7. van Wijck K et al. Novel multi-sugar assay for site-specific gastrointestinal permeability analysis: A randomized controlled crossover trial. Clin Nutr. 2013;32(2):245-51. Ganda Mall JP et al. Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress? BMC Geriatr. 2018;18(1):75. Ganda Mall JP et al. Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptoms. Sci Rep. 2018;8(1):13404. Ganda Mall JP et al. A β-glucan-based dietary fiber reduces mast cell-induced hyperpermeability in ileum from patients with crohn's disease and control subjects. Inflamm Bowel Dis. 2017;24(1):166-78.