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The role of the gut microbiota on allergy development in early life

The world is currently in the grip of an allergy pandemic. The prevalence of allergic diseases, such as food allergy, atopic eczema, allergic rhinitis and asthma, is rising dramatically worldwide in both developed and developing countries, currently affecting 30–40% of the population¹. The global rise of food allergy is particularly problematic in infants, who are bearing the brunt of this rising trend².

CMA is one of the most common childhood food allergies, affecting up to 5% of the population³. Although most infants with CMA outgrow their allergies by school age, an increasing number may have persistent symptoms or develop other allergic conditions over time, also referred to as the allergic march²⁻⁴.

Gut microbiota and the immune system

Microbial interactions are important drivers in the maturation of the immune system, with 70–80% of immune cells residing in the gut⁵. The gut microbiota provides many useful functions including protection from harmful pathogens, strengthening the body’s immune defences and performing vital metabolic tasks⁶.

The immune system develops quickly during the first 1000 days of life; developing and maintaining a balance between the gut microbiota and the immune system is essential to maintain health, especially in infants and children⁷.

The development of allergic diseases is influenced by genetic, environmental factors and transmission from the mother to the fetus. These play a critical role in the development of the immune system and the gut microbiota.

Factors which influence gut microbiota in early life⁸⁻¹⁰

    – Gestational age
    – The maternal environment
    – Delivery mode (vaginal or caesarean)
    – Nutrition (breast vs. formula feeding)
    – Use of antibiotics
    – Diet
    – Air pollution

The impact of gut microbiota dysbiosis on health and the development of allergy

The gut of a healthy breast-fed infant is typically dominated by bacteria of the Bifidobacterium species. These species are first transmitted from the mother during birth and via the breast milk¹¹⁻¹².

In addition to bacteria, breast milk also contains non-digestible oligosaccharides that are readily consumed by these same species of Bifidobacteria. By contrast, C-section delivery, use of antibiotics and formula-feeding can lead to a loss of these beneficial microbial organisms, and the expansion of pro-inflammatory pathobionts, many of which are species of Proteobacteria or Clostridium, e.g. C. perfringens and C. difficile¹¹⁻¹². These changes result in a shift in metabolic capacity, and activity of the gut microbiota and can lead to health consequences in later life¹³.

Disruption of the gut microbiota in early life has been linked with numerous clinical disorders such as asthma, metabolic syndrome, cardiovascular disease and obesity¹⁴. Many studies have shown that abnormal gut microbiota trajectories in infants may delay the development of oral tolerance and these play an important role in the development of food allergies, such as CMA¹⁵. Infants with food allergies such as CMA have been shown to have low levels of bifidobacteria and lactobacilli in their gut microbiota compared with healthy, breast-fed infants¹⁶.

Nutritional support for infants with CMA

Nutritional support is an essential part of the clinical management of infants with CMA.

CMA can present with a variety of symptoms, generally affecting the respiratory tract, the skin and the GI tract. It is classified according to the different immune responses, which include IgE-mediated (immediate) or cell mediated/non IgE-mediated (delayed) reactions and is associated with the development of other allergies³.

Recognising that breastfeeding is not always possible, ways to support the development of the microbiota of formula-fed infants have been sought, resulting in the addition of prebiotic oligosaccharides and specific probiotic strains — alone or in combination — in several commercially available infant formulas¹⁷⁻¹⁸.

A growing amount of clinical evidence shows that pre- and probiotics can have beneficial effects in infants at risk of, or living with allergies. Pre- and probiotics aim to influence the status of the tissue directly, or indirectly, via the gut microbiota thereby aiming to prevent the onset of an allergic disease¹⁹⁻²⁰.

Future of allergy management for CMA patients

The mainstay of dietary management of CMA infants is the avoidance of all cow’s milk and cow’s milk protein-based infant formulas. Breastfeeding is the gold standard for infant nutrition, however it may not always be possible for all CMA infants.

Therefore healthcare professionals may prescribe specialised formulations based on hydrolysed protein or amino acids for dietary management.

Due to the recognition that there is gut microbiota dysbiosis in allergy, there is a compelling rationale for the addition of both pre- and probiotic ingredients to formula for infants with CMA. A blend of pre- and probiotics is termed synbiotics. Synbiotics allude to a synergy in which the prebiotic compound selectively stimulates the colonization of the probiotic bacteria and other bifidogenic bacteria²¹.

Nutricia believes that there is a strong rationale to include pre-, pro- and synbiotics in the diet of these infants and has an extensive clinical trial programme underway investigating the role of these ingredients in the primary prevention and dietary management of CMA. Nutricia continues to collaborate with global experts to further its understanding of the impact of nutrition on food allergy.

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IMPORTANT NOTICE: Breastfeeding is best for babies. Infant formula is suitable from birth when babies are not breastfed. Follow-on milk is only for babies over 6 months, as part of a mixed diet and should not be used as a breastmilk substitute before 6 months. We advise that all formula milks including the decision to start weaning should be made on the advice of a doctor, midwife, health visitor, public health nurse, dietitian, pharmacist or other professional responsible for maternal and child care. Foods for special medical purposes should only be used under medical supervision. May be suitable for use as the sole source of nutrition for infants from birth, and/or as part of a balanced diet from 6–12 months. Refer to label for details.

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