Naturally Occurring Oligosaccharides

Human milk oligosaccharides (HMO) have been shown to exhibit beneficial properties with respect to the development of the infant gut microbiota. They have a non-nutritive function as they are indigestible by the host and serve as growth factors for gut bacteria, i.e., Bifidobacterium infantis [84]. Breastfed infants show less diarrhea and fewer intestinal infections, benefits which have been attributed to the presence of HMO. As such, there is a heightened interest in finding sources of oligosaccharides similar to those present in human milk that could be used to improve the current infant formula oligosaccharide (OS) profile.

Recent research has demonstrated that dairy streams such as whey permeate contain complex bovine milk oligosaccharides (BMO) similar to HMOs (Figure 4).

Structural diversity of human milk oligosaccharides (HMO) and bovine milk oligosaccharides (BMO). Adapted from (86)

Figure 4. Structural diversity of human milk oligosaccharides (HMO) and bovine milk oligosaccharides (BMO). Adapted from (86).

It is expected that, due to similarities in their structures, BMO might have similar prebiotic functions as the ones observed in HMO (Barile, 2009). Thus far, it has to be shown that BMO support bacterial growth, prevent pathogen growth, exhibit antiviral properties, and have brain development and immunomodulatory effects [85]. Barile et al. [11] first identified 15 BMO in whey permeate, of which eight are neutral and seven are acidic. Later it was shown that whey permeate obtained by pilot-scale fractionation contains 24 oligosaccharide compositions [12]. Due to its high market value and recognized health benefits, an increasing interest in the direct isolation of sialic acids from whey permeate is arising [59].

The concentration of OS in both colostrum and mature bovine milk (1.6 g/L and 0.06 g/L, respectively) is 20 fold lower than in human colostrum and mature milk (20-23 g/L and 5-16 g/L, respectively). However, the vast quantities of whey and whey permeate produced by the cheese industry make whey permeate a promising source of bioactive OS [87].

The biggest challenge associated with the development of large-scale or industrial processes to recover OS from mammalian milks is to achieve a high degree of purity; more specifically to remove simple sugars that lack prebiotic activities such as lactose, glucose, and galactose, while simultaneously maximizing product recovery. Downstream isolation of OS can be simplified by enzymatic hydrolysis of lactose into glucose and galactose, with subsequent nanofiltration and extensive diafiltration [88-91]. Alternatively, removal of monosaccharides can be accomplished with graphitized carbon chromatography or size- exclusion gel filtration with greater degrees of purity [85]. However, for an economically viable application of large-scale chromatography to recover OS from dairy streams, resin costs must be minimized, which may represent up to 70% of the processing costs [92].

Bovine milk oligosaccharides have immediately tangible value in the market place. As of publishing, 1mg of 6’-siallylactose costs $226.50 and 1mg of 3’siallylactose costs $173.00 [93], and therefore could provide a value stream for the cheese processing industry.

The development of more environmentally friendly processes that are also economically viable is a key step towards the production of sufficient quantities of OS for clinical trials and better elucidation of the functionality of those compounds in vivo. In addition to producing a new generation of prebiotics, environmental issues associated with the disposal of oligosaccharide-containing waste streams and poor economic viability will be mitigated.

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