Dietary Oligosaccharides

What is the role of oligosaccharides such as galacto-oligosaccharides (GOS) and fructooligosaccharides (FOS) in the health and wellbeing of infants and indicate if there are any potential safety issues that may determine upper limits of addition to infant formulas?

Oligosaccharides are short polymers of monosaccharides. Some of the dietary oligosaccharides are fructo-, galacto- and mannan-oligosaccharides. Fructo-oligosaccharides are made up of short fructose chains. Galacto-oligosaccharides consist of short chains of galactose molecules. They are known to support the growth of bifidobacteria in the large intestine. Bifidobacteria is essential for the maintenance of gut health. Mannan-oligosaccharides are obtained from Saccharomyces cerevisiae and participate in immunomodulation and agglutination (Belorkar & Gupta 2016, p.82).

Milk oligosaccharides protect infants by functioning as receptor homologues thereby preventing the attachment of entero pathogens on the host receptors. Gluco-oligosaccharides and maltodextrin-oligosaccharides act as dietary fiber and helps to increase the bifidobacteria concentration in the infant faeces. However, infant food supplemented with oligofructose results in further increase in the concentration of bifidobacteria. This in turn helps to prevent colonic epithelial mucosa atrophy (Bode 2012, p.1147).

This report at first describes the role of fructo-oligosaccharide and galacto-oligosaccharide in the well-being of infants. Next, the report carries out critical analysis of research based on for and against of oligosaccharides in infant formula.

Human milk consists of high concentrations of oligosaccharides and other carbohydrates. Oligosaccharides are the third most abundant constituent present in human milk. Human milk consist of 21 different types of oligosaccharides, some of which are linear, while the others are branched. Some are composed of fructose and galactose, which are simple sugars, while others are composed of uronic acids, which are sugar derivatives (Newburg 2013, p.771). The gastro-intestinal flora of breast milk-fed infants mainly consist of lactobacilli and bifidobacteria. Unlike the presence of bifidobacteria in breast milk-fed infants, the gastrointestinal flora of formula milk fed infants generally consist of anaerobic bacteria like bifidobacteria and bacteroides (Turroni et al. 2012, p.e36957). In order to mimic the gastrointestinal flora of breast-fed infants or to mimic the breast milk composition, lactobacilli and oligosaccharides are included in the infant milk formulas. Oligosaccharides addition in infant milk formula, results in bifidobacteria becoming the predominant flora in the gastrointestinal tract of infants. This also results in significant increase in the concentration of lactobacilli. Such intestinal flora prevents gastrointestinal colonization by decreasing the gastrointestinal permeability and providing protection against translocation. The gastrointestinal flora also participates in stimulation of enterohepatic circulation. Moreover, Lactobacilli helps to digest lactose and the flora can also carry out the hydrolysis of complex carbohydrates. The flora also reduces the allergenicity associated with undigested proteins. Moreover, addition of 90% galactooligosaccharides and fructo-oligosaccharides in infant formula has been found to be useful in the prevention of eczema development in infants, who are at high risk of developing this medical condition. Moreover, oligosaccharides have also been found to increase absorption of minerals in the colon. The by-products resulting from bacterial fermentation of the oligosaccharides reduces the pH of the colon, which in turn increases the solubility and subsequent absorption of minerals in the colon (Holscher et al. 2012, p.95S).

Role of Oligosaccharides in Infant Well-being

The differences in gastrointestinal flora between infants who are fed breast milk and formula milk are due to a variety of reasons. This difference is credited to the presence of carbohydrate, protein, iron and phosphorus in human milk. The gastrointestinal microbiota contributes in host nutrition, pathogen protection, development of immune response and regulation of intestinal angiogenesis (Islam 2013, p.20). Infant formula generally consist of galacto-oligosaccharides, fructo-oligosaccharides and polydextrose. Standard infant formula consisting of 0.8g/dL of galacto- and fructo-oligosaccharides were close to mimicking the breast-fed plan. Moreover, galacto-oligosaccharides of 0.24 or 0.44g/100ml in infant starter formula and 0.5g/100ml in follow on formula was shown to stimulate the growth of both bifidobacteria and lactobacilli similarly to those observed in the case of breast fed infants (Sierra et al. 2015, p.89).  Supplementation of infant milk with oligosaccharides were not found to have any side-effects. Moreover, supplementation were also not associated with incidents like vomiti

What is the role of oligosaccharides such as galacto-oligosaccharides (GOS) and fructooligosaccharides (FOS) in the health and wellbeing of infants and indicate if there are any potential safety issues that may determine upper limits of addition to infant formulas?

Oligosaccharides are short polymers of monosaccharides. Some of the dietary oligosaccharides are fructo-, galacto- and mannan-oligosaccharides. Fructo-oligosaccharides are made up of short fructose chains. Galacto-oligosaccharides consist of short chains of galactose molecules. They are known to support the growth of bifidobacteria in the large intestine. Bifidobacteria is essential for the maintenance of gut health. Mannan-oligosaccharides are obtained from Saccharomyces cerevisiae and participate in immunomodulation and agglutination (Belorkar & Gupta 2016, p.82).

Milk oligosaccharides protect infants by functioning as receptor homologues thereby preventing the attachment of entero pathogens on the host receptors. Gluco-oligosaccharides and maltodextrin-oligosaccharides act as dietary fiber and helps to increase the bifidobacteria concentration in the infant faeces. However, infant food supplemented with oligofructose results in further increase in the concentration of bifidobacteria. This in turn helps to prevent colonic epithelial mucosa atrophy (Bode 2012, p.1147).

This report at first describes the role of fructo-oligosaccharide and galacto-oligosaccharide in the well-being of infants. Next, the report carries out critical analysis of research based on for and against of oligosaccharides in infant formula.

Human milk consists of high concentrations of oligosaccharides and other carbohydrates. Oligosaccharides are the third most abundant constituent present in human milk. Human milk consist of 21 different types of oligosaccharides, some of which are linear, while the others are branched. Some are composed of fructose and galactose, which are simple sugars, while others are composed of uronic acids, which are sugar derivatives (Newburg 2013, p.771). The gastro-intestinal flora of breast milk-fed infants mainly consist of lactobacilli and bifidobacteria. Unlike the presence of bifidobacteria in breast milk-fed infants, the gastrointestinal flora of formula milk fed infants generally consist of anaerobic bacteria like bifidobacteria and bacteroides (Turroni et al. 2012, p.e36957). In order to mimic the gastrointestinal flora of breast-fed infants or to mimic the breast milk composition, lactobacilli and oligosaccharides are included in the infant milk formulas. Oligosaccharides addition in infant milk formula, results in bifidobacteria becoming the predominant flora in the gastrointestinal tract of infants. This also results in significant increase in the concentration of lactobacilli. Such intestinal flora prevents gastrointestinal colonization by decreasing the gastrointestinal permeability and providing protection against translocation. The gastrointestinal flora also participates in stimulation of enterohepatic circulation. Moreover, Lactobacilli helps to digest lactose and the flora can also carry out the hydrolysis of complex carbohydrates. The flora also reduces the allergenicity associated with undigested proteins. Moreover, addition of 90% galactooligosaccharides and fructo-oligosaccharides in infant formula has been found to be useful in the prevention of eczema development in infants, who are at high risk of developing this medical condition. Moreover, oligosaccharides have also been found to increase absorption of minerals in the colon. The by-products resulting from bacterial fermentation of the oligosaccharides reduces the pH of the colon, which in turn increases the solubility and subsequent absorption of minerals in the colon (Holscher et al. 2012, p.95S).

Variations in Gastrointestinal Flora in Breastfed and Formula-fed Infants

The differences in gastrointestinal flora between infants who are fed breast milk and formula milk are due to a variety of reasons. This difference is credited to the presence of carbohydrate, protein, iron and phosphorus in human milk. The gastrointestinal microbiota contributes in host nutrition, pathogen protection, development of immune response and regulation of intestinal angiogenesis (Islam 2013, p.20). Infant formula generally consist of galacto-oligosaccharides, fructo-oligosaccharides and polydextrose. Standard infant formula consisting of 0.8g/dL of galacto- and fructo-oligosaccharides were close to mimicking the breast-fed plan. Moreover, galacto-oligosaccharides of 0.24 or 0.44g/100ml in infant starter formula and 0.5g/100ml in follow on formula was shown to stimulate the growth of both bifidobacteria and lactobacilli similarly to those observed in the case of breast fed infants (Sierra et al. 2015, p.89).  Supplementation of infant milk with oligosaccharides were not found to have any side-effects. Moreover, supplementation were also not associated with incidents like vomiting, regurgitation or crying in the infants. However, some side-effects associated with galacto-oligosaccharide supplementation but not directly associated with galacto-oligosaccharide intake was abdominal discomfort, vomiting and increased gas production (Lasekan et al. 2015, p.3022).

This part of the report is a critical analysis of some of the research evidences that provide information about the role and effects of oligosaccharides supplemented in infant milk formula. The research articles used are titled: “Effects of Pre-biotic containing infant formula on gastrointestinal tolerance and fecal microbiota in a randomized controlled trial”, “Oligosaccharides in infant formula: more evidence to validate the role of prebiotics”, “Effect of the specific infant formula mixture of oligosaccharides on local immunity and development of allergic and infectious disease in young children: randomized study”.

The objective in case of the first study was to evaluate gastrointestinal tolerance, fecal microbiota, concentration of short chain fatty acids and pH of infants fed with formula milk with or without the addition of prebiotics like oligosaccharides. In this study, a randomized clinical study was carried out where formula fed infants were compared with infants fed with breast milk. The formula fed infants were fed with formula milk containing 4g/L of galacto-oligosaccharides and fructo-oligosaccharuides in the ratio of 9:1. The concentration of fecal bacteria, short chain fatty acids and pH were assessed at 0, 3 and 6 weeks intervals. The concentration and number of bifidobacteria were found to be higher in the case of infants fed with infant formula containing 4g/L of fructo – and galacto -oligosaccharides than the infants who were fed the control formula lacking the oligosaccharides. Moreover, the proportion of intestinal bifidobacteria were more or less the same as in the case of infants fed with breast milk. Apart from these the concentration of Clostridium difficle was found to be higher in the case of formula fed infants than those fed with control or breast milk. Additionally, the feces of formula fed infants had high concentrations of butyrate, acetate, propionate and short chain fatty acids when compared to those fed with breast milk. Fecal pH of infants fed with formula milk was lower than those who were fed with control milk. Thus, this study revealed that formula milk containing oligosaccharides were associated with increased abundance of bifidobacteria, reduced fecal pH and were well tolerated by the infants (Holscher et al. 2012, p.95S).

Supplementation of Infant Milk with Oligosaccharides

The second article is a review that shows the effectiveness of oligosaccharides when added in infant formula preparations. According to this study, prebiotics when added to infant formula had a biofidogenic effect on the intestinal gut microbiota of infants. Galacto-oligosaccharides were found to be favorable for the growth of Bifidobacterium but relatively poor growth was observed in the case of oligosaccharides like inulin, maltodextrin or polydextrose. Moreover, formulas containing oligofructose and fructose-oligosaccharide as well as galactose-oligosaccharide and fructose-oligosaccharide were found to have a similar bifidogenic effect to that of breast milk but was higher when compared to that of standard formula without oligosaccharides. In pre-term infants, formula supplemented with fructose-oligosaccharide was found to have positive effects on the growth of Bifidobacterium. This also resulted in a substantial decrease in the number of Enterococci and Escherichia coli. Moreover, the impact of the oligosaccharides were found to be much higher when they were administered at early infancy. Formula milk consisting of 0.24g/100ml and 0.44g/ml of galactose-oligosaccharide were found to reduce fecal pH to values more or less similar to that of breast milk. The concentration of short chain fatty acids produced were also similar in the case of oligosaccharide supplemented infant formula and breast milk. Oligosaccharides were also found to increase stool frequency and weight, apart from affecting the stool consistency and transit time. Standard infant milk formula containing 4g/l of galacto-oligosaccharides helped to improve stool consistency, which were similar to those observed in the case of breast fed infants. The stool consistency of the infants fed with only a mixture of fructose-oligosaccharide were not affected, while a mixture of fructo – and galacto -oligosaccharides had a significant effect. Another study revealed that supplementation with 5g/l of galacto-oligosaccharides resulted in higher stool frequency and consistency. However, a contradictory result was obtained in another study, which revealed that 5g/l of galacto-oligosaccharides had no effect on stool frequency and also decreased the infant stool consistency. The skin fold thickness of infants were found to be larger in the case of infants fed with breast milk than those fed with supplemented formula milk. Another study revealed no significant differences in the infant growth rates fed with supplemented or standard infant formula (Sierra et al. 2015, p.89). Oligosaccharides increase the number of Bifidobacterium, which in turn promotes enhancement of the immune system. However, according to Scalabrin et al. (2012), no noteworthy differences in the concentration of secretory IgA were observed in the case of oligosaccharide supplemented formula, when compared with that of the control groups. However, another study revealed that oligosaccharides reduced colitis by regulating the trafficking and function of natural killer cells (Gopalakrishnan et al. 2012, p.1336). Moreover, prebiotic supplementation helped to reduce the atopic dermatitis development in infants, however, there is no study to validate the atopic dermatitis preventive effects of oligosaccharides. The beneficial effects associated with the use of oligosaccharides in infant formula to prevent allergies and infections are not conclusively determined and thus further research is needed to validate this fact (Vandenplas, Zakharova & Dmitrieva 2015, p.1339).

Research-based Analysis of Effects of Oligosaccharides in Infant Milk Formula

The objective of the third article is to determine the efficacy of oligosaccharide enriched infant formula with respect to standard formula in enhancing the digestive immunity and prevent allergic diseases and infections. The infants were divided into three groups, which were breast fed, oligosaccharide formula fed and standard fed. The concentration of Bifidobacteria and Lactobacilli were found to be similar in the case of infants fed with either breast milk or supplemented formula milk. Moreover, the infant allergies were also lower in the case of infants fed with either breast milk or oligosaccharide supplemented formula milk but was higher in the case of standard formula fed infants. The mixture of short chain galacto-oligosaccharides and long chain fructo-oligosaccharidesin the ratio 9:1, were found to positively affect the digestive immunity similar to breast milk compositions (Ivakhnenko & Nyankovskyy 2013, p.398).

Keeping in mind the health benefits linked with breast feeding, policies have been generated in Australia and New Zealand, which deals with reducing the barriers to breastfeeding. These include restrictions to infant formula use. However, some infants require infant formula as their only source of nutrition and as a result, such infant formula products that are available to the population are closely regulated products. Infant formula products produced  in Australia and New Zealand are under the standard regulation 2.9.1. According to this standard, an infant formula is defined as “a product based on milk or other edible food constituents of animal or plant origin which is nutritional adequate to serve as the principal liquid source of nourishment for infants”. Moreover, infant formula is regulated in the United States by specific regulations or legislations that provide a set of nutrients to be added in infant formula. These are managed by the US food and drug administration. The permitted components to be added to the infant formula includes oligosaccharides, lutein, polyunsaturated fatty acids like omega 3 and 6, nucleotides, among others (Ris.pmc.gov.au 2018). According to the FDA, fructo-oligosaccharidesare permitted to be added to various food products including infant foods. The maximum intended level of fructose-oligosaccharide in infant starter formulas is permitted by the FDA to be 400mg/100ml and 500mg/100ml in follow on infant formulas (Fda.gov 2018).

Conclusion

This report gives a description of the roles of oligosaccharides in the health promotion and well-being of infants. The report also provides a critical analysis of the research that deals with the effects of these oligosaccharides on the growth and health of infants when compared to breast milk and standard infant formulas without added oligosaccharides. Supplementation of formula milk with oligosaccharides were found to result in increased bifidogenic effect, which in turn helps to prevent the attachment of pathogenic microorganisms and in turn prevents the occurrence of infections. Some studies have reported the role of these oligosaccharides in the promotion of growth and prevention of allergies, however, with lack of sufficient data, it is necessary that further research be carried out before successfully claiming such beneficial effects of oligosaccharides on infant health

Reference List

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Bode, L 2012, ‘Human milk oligosaccharides: every baby needs a sugar mama’, Glycobiology, vol. 22, no.9, pp.1147-1162, doi: 10.1093/glycob/cws074

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Gopalakrishnan, A, Clinthorne, JF, Rondini, EA, McCaskey, SJ, Gurzell, EA, Langohr, IM, Gardner, EM & Fenton, JI 2012, ‘Supplementation with galacto-oligosaccharides increases the percentage of NK cells and reduces colitis severity in Smad3-deficient mice’, The Journal of nutrition, vol.142, no. 7, pp.1336-1342, doi: 10.3945/?jn.111.154732

Holscher, HD, Faust, KL, Czerkies, LA, Litov, R, Ziegler, EE, Lessin, H, Hatch, T, Sun, S & Tappenden, KA 2012, ‘Effects of prebiotic-containing infant formula on gastrointestinal tolerance and fecal microbiota in a randomized controlled trial’, Journal of Parenteral and Enteral Nutrition, vol. 36, no. (1_suppl), pp.95S-105S, doi: 10.1177/0148607111430087

Islam, MR 2013, ‘Bifidogenic Effect and the Immunity Power of Human Breast Milk’, Delta Medical College Journal, vol.1, no.1, pp.20-24, doi: 10.3329/dmcj.v1i1.14972

Ivakhnenko, OS & Nyankovskyy, SL 2013, ‘Effect of the specific infant formula mixture of oligosaccharides on local immunity and development of allergic and infectious disease in young children: randomized study’, Pediatria Polska, vol. 88, no. 5, pp.398-404, doi: 10.1016/j.pepo.2013.07.002

Lasekan, J, Baggs, G, Acosta, S & Mackey, A 2015, ‘Soy protein-based infant formulas with supplemental fructooligosaccharides: Gastrointestinal tolerance and hydration status in newborn infants’, Nutrients, vol. 7 no. 4, pp.3022-3037, doi: 10.3390/nu7043022

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Scalabrin, DM, Mitmesser, SH, Welling, GW, Harris, CL, Marunycz, JD, Walker, DC, Bos, NA, Tölkkö, S, Salminen, S & Vanderhoof, JA 2012, ‘New prebiotic blend of polydextrose and galacto-oligosaccharides has a bifidogenic effect in young infants’, Journal of pediatric gastroenterology and nutrition, vol. 54, no. 3, pp.343-352, doi: 10.1097/MPG.0b013e318237ed95.

Sierra, C, Bernal, MJ, Blasco, J, Martínez, R, Dalmau, J, Ortuño, I, Espín, B, Vasallo, MI, Gil, D, Vidal, ML & Infante, D 2015, ‘Prebiotic effect during the first year of life in healthy infants fed formula containing GOS as the only prebiotic: a multicentre, randomised, double-blind and placebo-controlled trial’, European journal of nutrition, vol. 54, no. 1, pp.89-99, doi: 10.1007/s00394-014-0689-9

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ng, regurgitation or crying in the infants. However, some side-effects associated with galacto-oligosaccharide supplementation but not directly associated with galacto-oligosaccharide intake was abdominal discomfort, vomiting and increased gas production (Lasekan et al. 2015, p.3022).