September 2011/Prepared Foods -- The goal of life sciences is to build an integrative view of diet and health and to apply this knowledge to improving health and preventing disease. To this end, it will be necessary to understand the targets in individual humans on which diet acts to actually improve their health and lower their risk of future disease. How could such targets be found?
Milk and lactation evolved under the constant Darwinian selective pressure to be nourishing, protective and supportive of the health of mammalian infants. The molecules, structures and mechanisms by which milk achieves its benefits to infants are now guiding scientists in the search for the targets of health for everyone. Whey is a unique product stream that can provide, in turn, the means to deliver targeted health benefits to the marketplace. The emergence of indigestible oligosaccharides as a component in milk that selects and nourishes a protective microbiota is a vivid example of the insights into diet and health that milk and whey provide. This research is changing the way scientists and technologists are viewing human health.
Whey: From Waste to Gold
Whey has been viewed as a secondary product from cheese production for centuries, yet little of its health value has been captured for humans--until recently. In the past century, the biological value has been under-appreciated; it was actually viewed as industrial waste. Ironically, the ability of whey to support microbial growth in waste streams was viewed as part of its problem.
Curds and whey are not the inventions of technologists, but of biology itself. The enzyme cheese-makers use to clot milk in order to obtain cheese is also present in the human infant’s stomach, where it induces the self-assembly of casein aggregates and the release of soluble components, through whey into the intestine. This ingenious strategy of separating milk within the infant is clearly part of the structural dynamics of milk’s nourishing properties. Whey is thus the means that provide bioactives in soluble form.
As scientists and technologists work to understand the targets of milk’s actions and deliver components to individuals other than infants, separating milk into components is a valuable strategy. Processing whey into concentrated components extends this logic into increasingly valuable products. The newly recognized value of whey proteins in the ingredient marketplace attests to the success of this approach. As yet, a profitable process for utilizing the residue from whey protein concentration, also known as whey permeate, has not yet been identified. Can anything be learned from whey’s prior success?
Beyond Essential Nutrients
The non-essential components of milk and their roles are being pursued1. Essential nutrients can be studied with relative ease, because their elimination from the diet of animals leads to overt deficiency in every individual. Non-essential nutrients and their functions, however, are valuable only in context, and research has not been as successful in defining the contexts in which non-essential nutrients are valuable. One such example is the free oligosaccharides in milk. In fact, one of the most remarkable properties of lactation is the elaboration of complex oligosaccharides that are free (i.e., not attached to other molecules and are not digestible by the infant). Why does milk contain indigestible components?
Milk is the output of a dynamic interplay between the resources of the mother and the needs of the infant. Everything in milk costs the mother. Given this maternal-infant conflict, it is astonishing that human milk contains oligosaccharides that are not digestible by the infant or the mother. The lack of detailed methodologies to measure their structures and abundance led to the initial conclusion that oligosaccharides were functionless.
Now, milk oligosaccharides clearly play an important role in orchestrating the intestinal ecosystem (microbiota), both supporting the growth of protective bacteria2, 3 and displacing pathogenic bacteria4, 5. The importance of the microbiota extends beyond protection from pathogens to various functions, including “education” of the immune system, guiding metabolism, even perhaps mood. Indeed, failure to acquire an appropriate beneficial microflora has been linked with allergies and chronic inflammatory diseases, such as irritable bowel diseases, as well as obesity and diabetes. At present, the only source of truly complex selective oligosaccharides is human milk--a fact strongly limiting the applicability of these bioactive compounds as ingredients. Where would these be obtained?
Alternative Sources of Milk Oligosaccharides
In the search for alternative molecules that would mimic as closely as possible the structural and functional characteristics of human milk oligosaccharides, the authors recently discovered bovine milk and whey permeate contain oligosaccharides structurally far more similar to human milk oligosaccharides than currently available prebiotics6-9. This discovery has lead to the research and development of these specific oligosaccharides as ingredients. Research results suggest concentrating oligosaccharides from whey permeate can be a cost-effective process for the valorization of whey permeate into high-quality, profitable, novel dairy ingredients. Implementing a systematic recovery of milk oligosaccharides from whey permeate would enable cheese makers to capture the value from this by-product, generating high-value ingredients and significant, direct economical revenue.
There is a pressing need for scientific research in the 21st century to build the detailed molecular, mechanistic and systemic knowledge of human health and disease. At present, there is a lack of understanding of what molecules, biomaterial components, structures and diets could do to prevent diseases, rather than cure them. Without a model for how to proceed, it is difficult to imagine a path forward. Fortunately, milk and lactation provide a myriad of examples to guide research into understanding diets for lifelong health, and whey is emerging as an industrial means to bring many of these innovations rapidly to market.
Acknowledgements. Support of the California Dairy Research Foundation, U.S. Department of Agriculture National Research Initiative Cooperative State Research Education and Extension Service Award 2008-35200-18776, National Institute on Environmental Health Sciences Superfund P42 ES02710, the Childhood Autism Risks from Genetics and the Environment Study Grant P01 ES11269, and National Institutes of Health–National Institute of Child Health and Human Development Awards 5R01HD059127 and 1R01HD061923.
1. German JB, et al. Bioactive components in milk. Current Opinion in Clinical Nutrition & Metabolic Care, 2002. 5(6): p. 653.
2. Ward RE, et al. In vitro fermentation of breast milk oligosaccharides by Bifidobacterium infantis and Lactobacillus gasseri. Appl Environ Microbiol, 2006. 72(6): p. 4497-9.
3. Locascio RG, et al. Comparative genomic hybridization of Bifidobacterium longum strains reveals broad conservation of milk utilization genes in subsp. infantis. Appl Environ Microbiol, 2010.
4. Newburg DS. Neonatal protection by an innate immune system of human milk consisting of oligosaccharides and glycans. J Anim Sci, 2009. 87(13 Suppl): p. 26-34.
5. Morrow AL, et al. Oligosaccharide compositions and use therof in the treatment of infection. United States Patent US 2007/0275881, date filed 6 December 2004, and date published 29 November, 2007. 2007.
6. Barile D, et al. Permeate from cheese whey ultrafiltration is a source of milk oligosaccharides. Int Dairy J, 2009. 19(9): p. 524-530.
7. Barile D, et al. Neutral and acidic oligosaccharides in Holstein-Friesian colostrum during the first 3 days of lactation measured by high performance liquid chromatography on a microfluidic chip and time-of-flight mass spectrometry. Journal of Dairy Science, 2010. 93(9): p. 3940-3949.
8. Tao N, et al. Variations in bovine milk oligosaccharides during early and middle lactation stages analyzed by high-performance liquid chromatography-chip/mass spectrometry. Journal of Dairy Science, 2009. 92: p. 2991-3001.
9. Zivcovic A. and Barile D. Bovine milk as a source of functional oligosaccharides for improving human health. Advances in Nutrition, 2011,2:1-6.