Gastroenterology, Volume 3 - Issue 1, June 2016

Specific nutrients, gut microbiota and health – how they are all connected Back

Professor Udo Herz, Professor Annamaria Staiano

Impact of prebiotics on intestinal microbiota, immunity and allergy: concept and clinical applications

ProfessorProfessor Udo Herz Udo Herz, Danone Nutricia Early Life Nutrition, Amsterdam, The Netherlands, and Associate Professor of Immunology and Laboratory Medicine, Philipps-University, Marburg, Germany

Allergies, including food allergies, in infants have increased substantially in the past decades. Allergies mostly start within the first months of life and are associated with the introduction of food, including exposure to cow’s milk or cow’s milk-based infant formula. Sometimes they progress into lifelong clinical manifestations, often referred to as the ‘allergic march’. Although manageable, no curative therapy has yet been developed. Therefore, primary allergy prevention strategies focus on preventing the first steps in the allergic march, often focusing on exposure to the food proteins (including cow’s milk), especially in infants at risk.

Allergy prevention in infants and children is an active area of research, and a number of studies have focused on either completely avoiding or reducing early exposure to food proteins in at-risk infants. Most expert committees conclude that in infants, there is evidence to support modifying dietary exposure to protein by using extensively or partially hydrolysed formula instead of intact cows’ milk protein formula to reduce the risk of allergies, however the results in other meta-analyses and guidelines are not consistent.1,2

Differences in the studies using hydrolysed formula in primary allergy prevention could relate to the clinical endpoints assessed and/or the type of formula used. The clinical manifestations of food allergies, including eczema, are highly complex, differing in their age of onset, pathogenesis (ranging from acute to chronic phases), severity and natural history, and involve many factors beyond allergy. Recent insights indicate that the primary abnormality in eczema is that it is a skin-barrier defect; allergic sensitisation is a secondary phenomenon that increases the severity and longevity of atopic disorders.3 Thus, interventions that reduce sensitisation and/or induce tolerance may be more important for long-term outcomes.4 In addition, beyond the hydrolysis of cow’s milk proteins, other substances have been added (eg prebiotics, probiotics) that may have an impact on the development of allergies. The effects of these changes in infant formula composition are not considered in most meta-analyses. This situation calls for a more differentiated approach to understanding the pathophysiology and the efficacy of nutritional intervention strategies in primary allergy prevention.

Although the pathological mechanism largely differs between the clinical manifestations, they share the fact that the immune system reacts towards normal food proteins (there is a loss of tolerance). Early in life the infant is exposed to a wide variety of food and microbial antigens. While the human intestinal immune system is immature in this critical period, the infant must learn very quickly how to discriminate between potential disease-causing microbes and harmless antigens, such as food proteins and commensal bacteria. This physiological event leading to a controlled response to harmless food proteins is known as the induction of local and systemic immunological tolerance, or oral tolerance. Scientific progress in the last few years has highlighted the importance of the gut microbiota as a crucial factor for immune maturation and tolerance acquisition to foods (recognising them as ‘harmless’). Low gut microbial diversity and disturbances in gut colonisation patterns during infancy and childhood have been associated with later onset of allergies.

Scientific progress in the last few years has highlighted the importance of the gut microbiota as a crucial factor for immune maturation and tolerance acquisition to foods.

Early-life nutrition has a substantial impact on the developing gut microbiota, which responds rapidly to dietary change. There is evidence that the addition of prebiotics such as short-chain galactooligosaccharides/long-chain fructooligosaccharides (scGOS/lcFOS [9:1]) to infant formula brings the gut microbiota of formula-fed infants closer to that of breastfed infants.5 The increase in number of bifidobacteria correlates with the amount of intestinal secretory immunoglobulin A (sIgA) in the infant gut.5,6 sIgA-dependent function at the intestinal surface barrier supports tissue repair, thereby contributing to an individual’s threshold for food allergy. The addition of prebiotics (scGOS/lcFOS [9:1]) in infant formula is also associated with striking changes in production of microbial metabolites including short-chain fatty acid fermentation products.6 These metabolites have strong anti-inflammatory effects, both locally in the gut mucosa and beyond, and induce regulatory T-cells and tolerogenic dendritic cells, thereby mediating a protective effect against infections and allergies in both infants at ‘high risk’ and ‘low risk’ of allergy, based on their immediate family history of allergic disease.4,7–10 Most recently, the World Allergy Organization (WAO) guideline panel performed a systematic review and suggests the use of prebiotic supplementation for the prevention of allergy in not-exclusively breastfed infants.11

References

1. de Silva D, Geromi M, Halken S, et al, on behalf of the EAACI Food Allergy and Anaphylaxis Guidelines Group. Primary prevention of food allergy in children and adults: systematic review. Allergy 2014;69:581–9.
2. Boyle RJ, Ierodiakonou D, Khan T, et al. Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis. BMJ 2016;352:i974.
3. Bieber T, Akdis C, Lauener R, et al. Global Allergy Forum and 3rd Davos Declaration 2015. Atopic dermatitis/eczema: challenges and opportunities toward precision medicine. Allergy 2016;71:588–92.
4. Boyle RJ, Tang ML-K, Chiang WC, et al. Prebiotic-supplemented partially hydrolysed cow’s milk formula for the prevention of eczema in high-risk infants: a randomized controlled trial. Allergy 2016;71:701–10.
5. Knol J, Scholtens P, Kafka C, et al. Colon microflora in infants fed formula with galacto and fructo-oligosaccharides: more like breast-fed infants. J Pediatr Gastroenterol Nutr 2005;40:36–42.
6. Bakker-Zierikzee AM, Tol EA, Kroes H, et al. Faecal sIgA secretion in infants fed on pre- or probiotic infant formula. Pediatr Allergy Immunol 2006;17:134–40.
7. Arslanoglu S, Moro GE, Boehm G, et al. Early supplementation of prebiotic oligosaccharides protects formula-fed infants against infections during the first 6 months of life. J Nutr 2007;137:2420–4.
8. Arslanoglu S, Moro GE, Schmitt J, et al. Early dietary intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and infections during the first two years of life. J Nutr 2008;138:1091–5.
9. Grüber C, van Stuijvenberg M, Mosca F, et al. Reduced occurrence of early atopic dermatitis because of immunoactive prebiotics among low-atopy-risk infants. J Allergy Clin Immunol 2010;126:791–7.
10. Ivakhnenko OS, Nyankovskyy SL. Effect of the specific infant formula mixture of oligosaccharides on local immunity and development of allergic and infectious disease in young children: randomized study. Pediatr Pol 2013;88:398–404.
11. Cuello-Garcia CA, Fiocchi A, Pawankar R, et al. World Allergy Organization-McMaster University Guidelines for Allergic Disease Prevention (GLAD-P): Prebiotics. World Allergy Organ J 2016;9:10.