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Empower the Immune System with Good Nutrition

Prof. Yvan Vandenplas
Dr. Sanjeev Ganguly
12 Sep 2019
The nutrition infants receive during the first 1,000 days (in utero and up to 2 years) is crucial in laying the foundations for good health later in life. In a dinner symposium sponsored by Nestlé Nutrition Institute and chaired by A/Professor Anne Goh, President of the Singapore Paediatric Society, experts in paediatric nutrition discussed the role of probiotics, HMOs, and proteins in the growth and future health of infants and the development of their immune system.

Prof Yvan

Probiotics are living microorganisms that, when ingested in sufficiently large amounts, have a health-promoting effect on the host. Probiotics are present in human breast milk. Common examples of probiotics include members of the genus Bifidobacterium (B longum, B breve, and B infantis [B lactis or BB12]), Lactobacillus (L casei, L rhamnosus [GG], L reuteri, and L plantarum), and the yeast Saccharomyces boulardii.

Probiotic potential of B lactis
Among these probiotics, B lactis is noteworthy as being supported by robust clinical evidence. B lactis reduces pathogenic bacteria and promotes the prevalence of beneficial microbiota in the gut through the following mechanisms:1-3
• Competes against pathogenic bacteria for nutrients and available epithelial surfaces
• Produces organic acids that reduce the pH in the colon
• Produces bacteriocins which are antimicrobial proteinaceous compounds
• Increases levels of immunoglobulin A (IgA)

The immunomodulatory properties of oral supplementation of B lactis has been demonstrated clinically in preterm infants. In a double-blind, placebo-controlled, randomized clinical trial (RCT), preterm infants received orally administered B lactis or placebo for 3 weeks. At the end of the study, the probiotic group had higher levels of faecal IgA (p=0.021) and lower levels of the inflammatory marker, faecal calprotectin (p=0.041), compared with placebo.4 Furthermore, several clinical trials have shown that B lactis supplementation significantly reduces the risk of infant diarrhoea and infections in infancy including respiratory tract infections, non-specific gastrointestinal infections, and necrotizing enterocolitis.5-9

2’FL: An important HMO for bifidobacteria
The growth and proliferation of beneficial bacteria such as bifidobacteria are supported by human milk oligosaccharides (HMOs) – bioactive oligosaccharides that are structurally unique from non-human oligosaccharides (ie, galacto-oligosaccharides, fructo-oligosaccharides, or pectin-derived acidic oligosaccharides). The HMO 2’-fucosyllactose (2’FL) is the most abundant HMO in human breast milk and, as a known substrate of beneficial bacteria, is associated with the colonization of the infant gut with bifidobacteria.10

A double-blind RCT demonstrated the benefit of HMO supplementation (2’FL and lacto-N-neotetraose) on the gut microbiota of full-term infants. In this study, the relative abundance of bifidobacteria in the stool of infants who received HMO supplementation was significantly higher than in control infants and was similar to levels in breastfed infants (Figure 1).11 Furthermore, the relative abundance of potentially pathologic taxa, such as Escherichia and Peptostreptococcus, were significantly reduced compared with controls.

Empower Fig01

HMOs such as 2’FL also improve host defence by strengthening the gut barrier function, preventing bacterial adhesion, and facilitating the elimination of pathogens.12,13 These protective effects of 2’FL are beneficial in preventing diarrhoea in infants. A study on breastfed infants found that medium or high levels of 2’FL in maternal milk were associated with significantly lower rates of Campylobacter diarrhoea and all-cause diarrhoea compared with low 2’FL levels (p<0.01 for both) (Figure 2).14

Empower Fig02

Conclusion
The makeup of the gut microbiota in infants has long-lasting impact on their future health, including their immunity, metabolism, and intestinal health. Substantial exposures during the first years of life can significantly alter the balance of gut microbiota; hence, exposures that promote symbiosis, including breastfeeding and, if necessary, appropriate probiotics (eg, B lactis) and prebiotics (eg, 2’FL), should be underscored.

References:
1.
Cheikhyoussef A, et al. Int J Food Microbiol 2008;125:215-222. 2. Agastoni C, et al. J Pediatr Gastroenterol Nutr 2004;38:365-374. 3. Holscher HD, et al. JPEN J Parenter Enteral Nutr 2012;36(Suppl 1):106S-117S. 4. Mohan R, et al. Pediatr Res 2008;64:418-422. 5. Chouraqui JP, et al. J Pediatr Gastroenterol Nutr 2004;38:288-292. 6. Braegger C, et al. J Pediatr Gastroenterol Nutr 2011;52:238-250. 7. Taipale T, et al. Br J Nutr 2011;105:409-416. 8. Taipale TJ, et al. Pediatr Res 2016;79:65-69. 9. Bin-Nun A, et al. J Pediatr 2005;147:192-196. 10. Lewis ZT, et al. Microbiome 2015;3:13. 11. Berger B, et al. FASEB J 2016;30(Suppl 1):275.7. 12. Angeloni S, et al. Glycobiology 2005;15:31-41. 13. Bode L. Glycobiology 2012;22:1147-1162. 14. Morrow A, et al. J Pediatr 2004;145:297-303.

Dr Sanjeev

Environmental factors during the first 1,000 days of life play a role in the programming of growth and development of a child through epigenetics. During this process, hormones, toxins, medications, the microbiome, and nutrient intake all influence the epigenetic processes that select the expression of genes that could dictate health outcomes, including the risk of lifetime obesity.1

Early protein intake and obesity risk
Focusing on nutrition, it is well-established that breastfed infants are less prone to obesity later in life compared with formula-fed infants. According to the early protein hypothesis, this may be related to differences in protein intake early in life, which has an important role in promoting appropriate growth. Breastmilk is a dynamic system that adapts to the decreasing growth velocity of infants as they grow older through a decrease in protein content over time.2 In contrast, formula-fed infants may receive higher amounts of proteins, which could lead to obesity-promoting programming mediated by insulin. High levels of amino acids promote the secretion of insulin and insulin-like growth factor 1.3,4 These hormonal signals dampen satiety and promote adipogenic activity, which lead to adipocyte formation and increased early weight gain and programming towards overweight and obesity.

This correlation between high protein intake and future obesity has been demonstrated in large longitudinal studies. In one study evaluating the nutritional intake and growth of healthy infants spanning over two decades, those who had high protein intake had significantly higher body mass indices (BMI) compared with those who had lower protein intake.5

Role of optimised protein formulas in protecting against obesity
Given the role of high protein intake on obesity risk, new-generation formulas that are lower in protein quantity but of high quality may be beneficial in minimizing this risk.6 However, since protein is an important nutrient in growing infants, low-protein infant formulas should satisfy several requirements:7
• High protein quality to ensure that infants’ amino acid requirements are satisfied
• Clinical proof of comparable growth patterns as in breastfed infants
• Clinical evidence of safety in infants

A European multicentre, double-blind RCT evaluated the impact of a low- vs a high-protein infant formula on the BMI of infants and their risk of obesity at age 6 years. The study included healthy infants randomized to receive formula with either high or low protein content during the first year of life. The total caloric intake between groups did not significantly differ. Breastfed infants were also enrolled as an observational reference group.

At the end of the study, the median BMI of children (aged 6 years at study end) who received low-protein formula was significantly lower compared with those fed with high-protein formula and was similar to that of breastfed infants (Figure 3). Furthermore, the prevalence rate of obesity was lower in the low- vs the high-protein group (4.4 percent vs 10 percent) (Figure 4). The study investigators proposed that the differences in BMI and obesity rates could be due to metabolic programming signals induced by proteins despite the similar caloric intake.

Empower Fig03_04

Importantly, multiple studies have shown that the use of low-protein infant formula still allowed infants to develop within the growth ranges recommended by the World Health Organisation (WHO).8 Furthermore, low-protein formula has been shown to have no adverse effects on the neurodevelopment of children evaluated at age 8 years.9 The European Food Safety Authority, recognising that the protein intake of infants are generally in excess of protein requirements, also recommends a reduction of protein quantity in infant formulas and follow-on formulas.10

Conclusion
Breastfeeding remains the best nutrition for infants to ensure they achieve optimal growth and health outcomes. However, if breastfeeding is not possible or the breastfeeding period is too short, health professionals should choose to recommend formulas with optimised protein (high quality, lower quantity) that have been clinically studied and approved. This could help in reducing the risk of obesity in childhood while helping them grow normally in line with WHO child growth standards.

References:
1.
Lucas A. NNI Workshop Series 2010;65. 2. Lönnerdal B, et al. J Nutr Biochem 2017;41:1-11. 3. Koletzko B, et al. Am J Clin Nutr 2009;89(Suppl):1502S-1508S. 4. Ong K, Dunger B. Eur J Endocrinol 2004;151(Suppl 3):U131-139. 5. Rolland-Cachera MF, et al. Int J Environ Res Public Health 2016;doi:10.3390/ijerph13060564. 6. Weber M, et al. Am J Clin Nutr 2014;99:1041-1051. 7. Trabulsi J, et al. Eur J Clin Nutr 2011;65:167-174. 8. Alexander DD, et al. Am J Clin Nutr 2016;104:1083-1092. 9. Escribano J, et al. Br J Nutr 2016;22:1-9. 10. EFSA. EFSA Journal 2014;12:3760.
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Most Read Articles
Prof. Vincent Wong, Prof. Ray Kim, Dr. Tan Poh Seng, 10 Sep 2019
Chronic hepatitis B (CHB) remains a major public health concern because of its worldwide distribution and potential adverse sequelae, including cirrhosis and hepatocellular carcinoma (HCC). At a recent symposium held during the GIHep Singapore 2019, Professor Vincent Wong from the Chinese University of Hong Kong and Professor Ray Kim from the Stanford University School of Medicine, Stanford, California, US, discussed antiviral treatments for CHB, with a focus on the novel agent tenofovir alafenamide (Vemlidy®). Dr Tan Poh Seng from the National University Hospital, Singapore, chaired the symposium.
Tristan Manalac, 2 days ago
Sleep deprivation impairs adolescents’ long-term retention of classroom material, according to a recent Singapore study.
Tristan Manalac, 3 days ago
A digital-first approach, iConnect, allows patients to have greater access to services and guidance and enables healthcare providers to deliver much better postdischarge care, according to Lim Cher Wee, chief operating officer of the Ministry of Health, Office for Healthcare Transformation of Singapore, in his presentation at the recently concluded AsiaPac19 Conference & Exhibition of the Healthcare Information and Management Systems Society (HIMSS 2019).
2 days ago
Better-quality diets facilitate healthy ageing, slowing down the accumulation of deficits, particularly functional deterioration, a recent study has found.