Nutritional Outlook/BASF eBook by William Ellis

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The manufacturer’s resource for dietary supplements & healthy foods and beverages

THE ROLE OF HMOs IN HUMAN NUTRITION

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formula—always with the objective to narrow the nutritional gap between human milk and cow’s milk-based infant formula.

Designed by Mothers, Discovered by Scientists Human Milk Oligosaccharides (HMO) is a breakthrough differentiator: they are the third largest solid component in human milk, following lactose and fat. The amount is about 300 times higher compared with bovine milk. HMOs were discovered many years ago, however, it was only during the last decades that detailed insights into the complexity of the structures were gained, thanks to the availability of more precise analytical methods. The HMO composition of human milk is complex and varies significantly among mothers, over the course of lactation and according to their genetic set-up. The HMO concentration in early milk is highest and it declines

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by about 30 percent over the course of lactation. In mature human milk, the content may still be as high as 5 – 20 g/L compared to less than 0.05 g/L of bovine milk. Today, more than 200 HMO molecules have been identified, of which 2’-fucosyllactose (2´-FL) is the most abundant in most mothers. Up to now, galactooligosaccharides (GOS) and fructooligosaccharides (FOS) have often been added to infant formula to mimic HMOs. However, both do not occur in human milk. On the other hand, fucose and sialic acid which appear to be important structural and functional components of HMOs are absent in infant formula with GOS/ FOS. Thus, the availability of HMOs with molecular structures identical to those occurring in human milk is a breakthrough in infant nutrition.

The First Superfood for Babies’ Healthy Development During infancy, HMOs are important to shape the microbiota by promoting the colonisation of beneficial bacteria, mainly bifidobacteria. More and more ongoing studies show the clinical relevance of deviations from “normal” microbiota, especially during early life (e.g., dysbiosis preceding allergic diseases, metabolic syndrome or obesity). Thus, developing a mi3

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More and more ongoing studies show the clinical relevance of deviations from “normal” microbiota, especially during early life (e.g., dysbiosis preceding allergic diseases, metabolic syndrome or obesity). crobiota close to that of breastfed infants is the objective. Healthy immune functions are a pre-requisite for the prevention of infections and allergies. About 10 years ago, it was found that Campylobacter diarrhea—one of the major causes of diarrhea during infancy— occurred less often in babies whose mother’s milk contained high levels of 2’-FL. In the meantime, mechanistic studies shed light on this observation: due to the specific molecular structure, 2’-FL is able to act as a decoy receptor for pathogens. Instead of binding to the carbohydrate receptors on the intestinal cell surfaces, pathogens bind to 2’-FL and the adhesion to the host cells—the first step of infections—can be prevented. Moreover, 2’-FL can directly modulate intes-

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tinal cell responses and the thus strengthen the mucous barrier. Recent data suggest that 2’-FL can directly attenuate inflammation in experimental models. This confirms HMOs as being an “innate” immune system of human milk whereby the mother protects the vulnerable newborn child. 2’-FL can also represent a novel preventative active to reduce mucosal inflammation associated with diverse bowel disorders. Allergies are on the rise in many countries and besides genetic predisposition, environmental factors play an important role. Observational studies suggest that fucosylated HMOs may have a preventive role in infants with high allergy risk. Further promising results stem from rodent models, in which 2’-FL was shown to have a positive effect on learning and memory functions when supplemented during infancy.

Human Milk Oligosaccharides: Precious Components for Infancy and Beyond Despite the encouraging results from clinical and experimental studies, HMO research is still in its infancy. Given the var-

Due to the selection of a stable fermentation strain, there is no need for the use of antibiotics during production and therefore, BASF’s 2’-FL is 100 percent free of antibiotics. 4

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ious functions and benefits already discovered for 2’-FL, this molecule is a promising ingredient not only for infants, but also for children and adults in various life-stages, meeting consumer’s desire for ingredient solutions inspired by nature. The availability of 2’-FL for use in infant formula is an important first milestone to make this happen. When developing the 2’FL fermentation at BASF, we focused on upscaling characteristics right from the start: the 2’-FL fermentation has been developed as a platform technology which is available for further molecules as well. BASF has successfully mastered the complete inhouse development of 2’-FL, based on the capabilities of our central research network in Ludwigshafen, Germany. Serving the infant formula market, product safety is clearly of utmost importance. This is exemplified in the way we deal with potential microbiological contaminations, considering the most rigid standards (e.g. (EC) 2073/2005). Due to the selection of a stable fermentation strain, there is no need for the use of antibiotics during production and therefore, BASF’s 2’FL is 100 percent free of antibiotics. BASF’s leadership in sciencebased solutions, production technology and operative excellence, ensures reliable and efficient production setup, providing the flexibility required to consistently meet customer needs, especially in fast-growing markets.Protecting our customer’s most precious and vulnerable consumers is a commitment we make in our vision to provide the right nutrients to the right people at the right time.

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INFANT FORMULA INGREDIENTS TRY TO BRIDGE THE BREASTMILK GAP

ew formulation challenges are more sensitive than designing a safe and wholesome infant formula. After all, this is one audience that depends on us completely to get things right. And as competition among brands heats up—with the stiffest competition coming from the breast itself—savvy parents increasingly, and justifiably, scrutinize everything they feed their littlest family members, holding infant formulas to the strictest standards of all. So now that “safe and wholesome” alone no longer cut it, infant formula brands have to ramp up the innovation to build a product that delivers what’s best for baby—which nowadays means what comes closest to the breastmilk ideal. None of which surprises Sigalit Zchut, PhD, chief scientist, Advanced Lipids, a joint venture of lipids companies AAK (Malmo, Sweden) and Enzymotec (Migdal HaEmeq, Israel). “Consumers naturally want the best for their kids,” she says. “Yes, quality has

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always been the number-one consideration when it comes to infant formula, but more often it’s not just about quality, but about quality plus specific nutritional benefits.” Benefits that bridge the breastmilk gap.

Going Global It’s no secret that sales of infant and baby nutrition products have trended flat in wealthy countries as women have embraced breastfeeding. But it’s a big world out there, and the global market for infant formula has almost tripled since 2006, Zchut says, currently boasting a retail value of over $45 billion. China alone accounts for almost half this value, making it the world’s largest infant formula market by far. “But we’re also seeing interesting developments in other regions,” Zchut observes. “In Latin America, for example, the market is currently worth around $2.2 billion, or 150,000 metric tons in volume, and significant growth is forecast, so it’s promising territory for formula companies.”

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Baseline Formula Regardless of the region a brand targets, the baseline goal in developing any infant formula is to create a product that’s safe beyond a doubt, and that provides the nutrients essential for an infant’s optimal development. Meeting that goal starts with the composition of the base powder, which supplies the formula’s protein and carbohydrate fractions, at 10%-15% and 52%-57% of the total formulation, respectively. “These fractions usually come from whole milk or a combination of skim milk and whey protein,” Zchut explains. As for the fat fraction—which typically clocks in at 22%-28% of the finished formula base—“it’s mostly sourced from vegetable oils, but sometimes partially from milkfat,” Zchut continues. Last but not least are the vitamins, minerals, and other micronutrients that bring a formula closer to nutritional completion. Though their relative proportion in the finished product is low—roughly 4%-6%, in total—“they’re just as crucial for the baby’s healthy development” as the formula’s other components, Zchut insists.

Setting Standards Currently, the nutrient content of infant formulas sold domestically falls under FDA purview and is based on recommendations from the American Academy of Pediatrics Committee on Nutrition. Present guidelines deem that all formulas made in the United States must contain protein, carbohydrates, fat, and linoleic acid. All formulas must also include vitamins A, C, D, E, K, thiamin (B1), riboflavin (B2), niacin (B3), pantothenic acid (B5), 6

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pyroxidine (B6), folic acid (B9), and cyanocobalamin (B12). Calcium, magnesium, iron, zinc, manganese, copper, phosphorus, and iodine are also required, as are the electrolytes sodium chloride and potassium chloride and some of the nucleotides found naturally in human breastmilk, like uridine, inosine, and cytidine. Regulatory tightening has improved formula compositions over the years, with one key change tracing back to the nutrient requirements specified in the Infant Formula Act of 1980, passed in response to a 1979 recall of chloride-deficient formulas that sickened thousands of infants and yielded enough lawsuits to get the regulations changed.

Breast Is Best But even with enhanced regulatory oversight and the laundry list of required nutrients, infant formulas don’t match the composition or nutritional potency of human breastmilk, which, Zchut concedes, “is the gold standard toward which every formula brand should strive. It provides the optimal nutrition for infants, delivering a perfect balance of nutrients that naturally meets every need in the first months of life.” But, notes Steen Lyck, global business director for HMO, DuPont Nutrition & Health (Madison, WI), “Human breastmilk is very complex, and it’s impossible to mimic its composition.” Zchut agrees. “Human milk contains a lot of biological components that are impossible to copy, such as immunoglobulins—antibodies produced by the mother to protect the infant from infections in early life,” she points out. Breastmilk is also always changing. “Its composition in the day after birth is different from its composition when the baby’s one,

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three, or six months old,” Zchut continues. “All that is very difficult to copy, and there are many more differences to count.”

Closing the Gap Yet despite the head start that millennia of evolution gave us in fine-tuning the nutritional perfection that is breastmilk, the infant nutrition industry has to work within the span of a product cycle. Even so, it’s making genuine strides in closing the gap between mom’s product and its own. “Infant formula has improved significantly over the past two decades thanks to scientific research that studies human milk composition on one hand, and clinical studies that test the effect of key ingredients on the wellbeing of the baby on the other,” Zchut says.

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“Infant formula has improved significantly over the past two decades thanks to scientific research that studies human milk composition on one hand, and clinical studies that test the effect of key ingredients on the wellbeing of the baby on the other.” – Sigalit Zchut, PhD, chief scientist, Advanced Lipids

Structured Fats

Beneficial Oligosaccharides

The result is the addition of “specialty” ingredients to formulas that wouldn’t have appeared there even a few years ago. Consider the industry’s efforts better to replicate the unique lipid structure of breastmilk. Most of the palmitic acid in human milk fat is attached to the central carbon in the fat’s glycerol backbone. SN2 palmitate or OPO (oleic and palmitic fatty acid structure) is a structured triglyceride that mimics this conformation, and, says Zchut, “We can now develop OPO from vegetable sources and offer it as an ingredient in formulas. By mimicking the fatty acid positioning of human milk, it delivers many of the same benefits.” A recent clinical trial involving INFAT, her company’s branded OPO ingredient, found that it enhanced fatty acid absorption to more closely resemble breastfeeding, she says. “Research also shows that it offers benefits for comfort, healthy growth, and immunity.”

Human milk oligosaccharides, or HMO, comprise another class of ingredients finding their way into infant formulas. These are a collection of indigestible short-chain carbohydrates—glucose, galactose, fucose, sialic acid, and N-acetyl-glucosamine among them—with pre-clinically and clinically validated benefits for infants. “Some of their healthful effects include promoting a Bifidobacteria-rich microbiome, creation of the building blocks for brain development, prevention of pathogens and viruses, and stimulation of the immune system,” says DuPont Nutrition & Health’s Lyck. “By introducing commercially produced HMO that are structurally identical to those found in breastmilk, we can narrow the gap between human milk and formula.” Granted, while human breastmilk contains hundreds of HMO, “We’re only introducing a few” in commercial formulas, Lyck con-

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cedes. “So there’s still a long way to go.” And the optimal levels at which to add them are still up for discussion. For example, the most abundant HMO in human breastmilk, appearing on average at 2.4 g/L, is 2’fucosyllactose (2’-FL). “But this varies a lot from woman to woman, region to region, and where the mother is in the lactation period,” Lyck explains. And while 2.4 g/L is the HMO addition level that FDA regulations approve in infant formulas, the EU approves only half that amount, basing its decision on the few infant clinical studies carried out so far. In 2016, two companies, DuPont and Inbiose (Ghent, Belgium), entered into a joint development and licensing agreement for the exclusive rights to produce and commercialize a 2’-FL ingredient that is “fully identical to the 2’-FL HMO found in human milk.” The companies announced the ingredient had been granted EU Novel Food regulatory approval for infant formulas in December 2017 and U.S. Generally Recognized as Safe (GRAS) status in April 2018. In May, another company, FrieslandCampina Domo (Amersfoort, The Netherlands), announced its new 2’-FL ingredient received EU Novel Food approval and GRAS status in the U.S. In 2016, FrieslandCampina Domo partnered with U.S.-based carbohydrates firm Glycosyn to develop a range of infant nutrition ingredients. FrieslandCampina Domo says that this new 2’-FL ingredient will be the first in a range of HMOs that the companies are developing. The company also says that it is currently building a new manufacturing plant in Italy dedicated to large-scale production of 2’-FL HMOs, which is slated for completion by the end of the year. The new 2’-FL ingredient will be mar8

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“Infant-specific probiotics have been added to formula to mimic the microbiome that’s transferred from mother to baby during birth and breastfeeding.” – Steen Lyck, global business director for HMO, DuPont Nutrition & Health

keted under the brand name Aequival.

Critical Membranes Because the fat source used in most infant formulas are plant-derived oils, they lack an important tri-layered protein and lipid structure that encases every milk fat globule found in human, as well as bovine, milk. This membranous structure, known as milk fat globule membrane (MFGM), is also rich in bioactive gangliosides, phospholipids, glycolipids, glycoproteins, and carbohydrates with demonstrated benefits for an infant’s brain development, gut health, nutrient absorption, and immune function. A 2017 review1 of studies examining the effects of adding MFGM to infant formulas concluded, “Available evidence from model studies and clinical trials indicates the potential of beneficial effects of the combination of bioactive compounds or any specific component of MFGM to improve infant formulas. Importantly this relates to actual health during infancy and may contribute to optimizing the long-term programming of the immune system and cognitive functions.”

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While the researchers called for more study before implementing widespread addition of MFGM to infant formulas, they do note, “The availability of some corresponding components from bovine milk or biotechnological production offers the possibility to include these components into formulas and to further close the gap between formula-feeding and breast-feeding.” Something to keep your eye on for the future.

tective shell that allows it to remain dormant through most manufacturing processes and gastric transit, and has a three-year shelf life, making it an excellent choice for powdered infant and toddler formulas,” Quilter says. Just as impressive, in 2017 it was the first B. coagulans probiotic to receive FDA GRAS status for use in infant formula.

Building Baby’s Microbiome

That matter of FDA go-ahead is no small consideration for formula manufacturers, and understandably so. “The regulation of infant formula is very rigorous because it’s the sole source of food for the newborn infant and is therefore an extremely sensitive type of food,” Zchut says. “It undergoes much more rigorous review by regulatory authorities than does food for adults.” Because regulations differ globally, how long it takes to get new ingredients approved varies, but you’re almost always looking at an expensive process that unfolds over a years-long horizon—“in some countries one to two years, and in others closer to five,” Lyck says. “This includes developing and documenting safety data, maybe clinical studies, documentation of a constant and safe process—all of this collected in a dossier and followed by approval of the dossier and publication.” But the trouble is worth it to start Junior out on the right footing. As Lyck says, “We know that the first 100 to 1,000 days in a baby’s life determine so many health aspects later in life, as well.”

As Lyck notes, “Infant-specific probiotics have been added to formula to mimic the microbiome that’s transferred from mother to baby during birth and breastfeeding.” And given the excitement surrounding their potential benefits for the broader public, curiosity about how they might help improve infants’ prospects seems like a logical extension. Indeed, says John Quilter, vice president and general manager, GanedenBC30 and Wellmune, Kerry (Beloit, WI), “Currently, three out of four U.S. consumers are aware of probiotics. As this awareness continues to grow both in the U.S. and globally, probiotics as an ingredient in infant formulas may become more commonplace.” And for good reason: “There are a variety of factors that can negatively affect the natural bacteria and digestive development of infants and toddlers,” Quilter explains. “Furthermore, babies are born with sterile digestive tracts and must work to build their beneficial gut bacteria and create a healthy microbiome.” Evidence suggests that probiotics can help. His company’s GanedenBC30 (Bacillus coagulans GBI-30, 6086) probiotic has scientific support for its digestive and immune benefits and, as a spore-former, “has a natural, pro9

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Jumping through Hoops

References: 1. Hans D et al. “Benefits of lactoferrin, osteopontin and milk fat globule membranes for infants.” Nutrients, vol. 9, no. 8 (July 28, 2017): 817

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OPTIMIZING INFANT HEALTH WITH HUMAN MILK OLIGOSACCHARIDES Human milk oligosaccharides show promise in infant health.

tarting from hour one, nutrition is a determining factor in an infant’s health and has short- and long-term effects on a child’s life overall. The World Health Organization (WHO) recommends exclusive breast feeding for up to six months because of its critical role in infant health. Research supports its ability to offer a highly protective effect on infant mortality, decrease the occurrence of respiratory and gastrointestinal infections, and improve neurodevelopment in children born premature or on-term. (1) Studies have shown the effect of breastfeeding on neurodevelopment and long-term cognitive outcome of preterm infants may persist into childhood, adolescence, and even adulthood. (2) The nutrients in breast milk, such as oligosaccharides, play an important role in this process. However, despite the recommendations of the WHO, breastfeeding rates remain low in many regions of the world. As a result,

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A 2019 review of animal studies suggest that probiotic microbes and HMOs alter the composition of the intestinal microbiota and may prevent disease in premature infants. (5) scientists have extensively studied the composition of human milk in order to narrow the nutritional gap between breast milk and infant milk formulas.

Human Milk Oligosaccharides Human milk consists of 87% water, 7% carbohydrate (including 1% – 2.4% oligosaccharides), 4% lipid, and 1% protein, as well as

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minerals and vitamins. The third most abundant solid component of breast milk, after lactose and lipids, is human milk oligosaccharides (HMOs). They are present in large quantities in breast milk—from 5 to 15 g/L—and have varied biochemical compositions (more than 130 different molecules have been identified so far). They may help protect children against infectious diseases and function to stimulate growth of healthy bacteria, i.e., the prebiotic effect; modulate certain immune reactions; and inhibit the growth of bacteria, viruses, and even parasites. (3) Several studies have reported HMOs modulate the intestinal microbiota, have an anti-adhesive effect against pathogens, modulate the intestinal epithelial cell response, and support the development of the immune system. (4) A 2019 review of animal studies suggest that probiotic microbes and HMOs alter the composition of the intestinal microbiota and may prevent disease in premature infants. (5) More specifically, a study published in Molecular Nutrition & Food Research found HMOs reduce the incident of necrotizing enterocolitis (NEC), a devastating disease that affects mostly the intestines of premature infants. (6)

2’-Fucosyllactose 2’-fucosyllactose (2’-FL) is the most abundant HMO in most mothers and one of the most widely studied. It has been associated with several health benefits in infant care, with infant diarrhea being one of the most prominent. A 2004 study analyzed data and banked samples from 93 breast-feeding mother-infant pairs who were studied from birth to age 2. (7) The researchers found infants whose mother’s milk contained high levels of 2’-FL had fewer occurrences of di11

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arrhea, specifically campylobacter diarrhea. In 2017, researchers analyzed 2’-FL in the breast milk samples of 266 mothers from the placebo group of a randomized, placebo-controlled trial studying pre- and probiotics as preventive measures against

A 2004 study analyzed data and banked samples from 93 breast-feeding mother-infant pairs who were studied from birth to age 2. (7) The researchers found infants whose mother’s milk contained high levels of 2’-FL had fewer occurrences of diarrhea, specifically campylobacter diarrhea. allergic disease in infants with high allergy risk. (8) The results showed infants born by C-section with a high hereditary risk for allergies may lower their risk of eczema when consuming breast milk with 2’-FL, compared with infant formula free of HMOs. A couple of clinical studies have examined the use of formulas supplemented with 2’-FL in infants. In a randomized, controlled, growth and tolerance study, formula-fed infants were administered one of three formulas—two of which contained varying levels of 2’FL—for four months. (9) Results showed the formulas with 2’-FL

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HMOs and Gut Health Approximately 48% of US consumers understand that good digestive health is linked to whole body health and are very interested in the use of food, drinks, and supplements to support healthy digestive function (1). As a result of strong consumer interest in digestive support, the digestive health category is expanding and shows no signs of slowing. The global supplement market for digestive support, for instance, has grown by 8% over the past few years; moreover, the number of new product launches has grown by 11% each year (1). Powders and capsule formulations are particularly strong drivers in the category, representing a combined 50% of new product launches. Prebiotics are an especially strong player in the category, either as a standalone formula or within probiotic combination probiotics. Between 2009 and 2018, the number of new global product launches with prebiotics as ingredients grew from 2,000 to 7,200 products annually, are thus are considered by many industry experts to be the future of the category. The uptick in interest in prebiotics is because of their unique role in the human nutrition; they provide nourishment for good bacteria and thus are critical for helping maintain healthy bacteria balance in the gut. One research-backed prebiotic, 2’-fucosyllactose (2’FL), is not only is beneficial to infant nutrition, but can support digestive health throughout life such as for inflammation support, supporting regular bowel movements, and benefiting bacterial balance in the gut. • In a two-week study of 100 healthy adults, supplementing with 2’FL increased the relative abundance of “good bacteria” like actinobacteria and bifidobacterium and reduced firmicutes and proteobacteria (2). • 2’FL supplementation contributed to the adaptive response of microbial colonies after intestinal resection in a small animal study (3). • 2’FL decreased LPS-dependent induction of inflammation-causing interleukin (IL)-8 caused by enterotoxigenic Escherichia coli. Mucosal inflammation is also associated with various inflammatory disorders of the mucosa (4). • 2’FL was found in a small-animal ex vivo study to reduce acute stress-induced gut dysmotility; stress can cause dysmotility in the gut (5). Research on these topics are ongoing and will continue to grow along with consumer interest in the use of 2’FL and other prebiotics for support digestive healthy throughout life.

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were well-tolerated; infants fed formula with 2’-FL showed growth and uptake similar to breast-fed infants. Separately, a randomized, double-blind control study published in The Journal of Nutrition investigated the effects of infant formula with 2’-FL on immune function in healthy term infants. (10) Similar to breastfed infants, infants fed 2’-FL-supplemented formulas exhibited lower plasma and ex vivo inflammatory cytokine profiles than those in the control group. A separate study examined the effects of infant formula supplemented with two HMOs, including 2’-FL, on infant growth, tolerance, and morbidity. (11) Healthy infants, 0 to 14 days old, were randomized to receive an intact-protein, cow’s milk-based infant formula, or the same formula with 1 g of 2’FL and 0.5 g/L lacto-N-neotetraose (LNnT). After six months, researchers concluded the infant formula with 2’FL and LNnT was safe, well-tolerated, and supported age-appropriate growth. They also found associations between consuming HMO-supplemented formula and lower parent-reported morbidity, particularly bronchitis, and medication use (antipyretics and antibiotics). Research continues to support the benefits of 2’-FL and its role in optimizing infant nutrition. And as more studies are conducted, knowledge of the positive effects of HMOs will broaden.

References: 1.

Clair-Yves Boquien. “Human Milk: An Ideal Food for Nutrition of Preterm Newborn” Front Pediatr. 2018;6:295 doi: 10.3389/fped.2018.00295 Pei JJ, Tang J. “A review on the relationship between breast milk nutrients and brain development in preterm infants” Zhonggu o Dang Dai Er Ke Za Zhi 2019;21(6):607-612 SPONSORED BY

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Ibid. Clair-Yves Boquien. “Human Milk: An Ideal Food for Nutrition of Preterm Newborn” Front Pediatr. 2018;6:295 doi: 10.3389/ fped.2018.00295

Hegar B, Wibowo Y, Basrowi RW, et al. “The Role of Two Human Milk Oligosaccharides, 2’-Fucosyllactose and Lacto-N-Neotetraose, in Infant Nutrition” Pediatr Gastroenterol Hepatol Nutr. 2019;22(4):330-340 doi: 10.5223/ pghn.2019.22.4.330

Underwood, MA. “Probiotics and Human Milk Oligosaccharides in Premature Infants” Neoreviews. 2019;20(1):e1-e11

Wang C, Zhang M, Guo H, et al. “Human Milk Oligosaccharides Protect against Necrotizing Enterocolitis by Inhibiting Intestinal Damage via Increasing the Proliferation of Crypt Cells” Mol Nutr Food Res. 2019 17:e1900262 doi: 10.1002/mnfr.201900262

Morrow AL, Ruiz-Palacios GM, Altaye M. “Human milk oligosaccharides are associated with protection against diarrhea in breast-fed infants” J Pediatr. 2004;145(3):297-303

Sprenger N, Odenwald H, Kukkonen AK, et al. “FUT2-dependent breast milk oligosaccharides and allergy at 2 and 5 years of age in infants with high hereditary allergy risk” Eur J Nutr. 2017;56(3):1293-1301 doi: 10.1007/s00394016-1180-6

Marriage BJ, Buck RH, Goehring KC, et al. “Infants Fed a Lower Calorie Formula With 2’FL Show Growth and 2’FL Uptake Like Breast-Fed Infants” J Pediatr Gastroenterol Nutr. 2015;61(6):649-58 doi: 10.1097/ MPG.0000000000000889.

10. Goehring KC, Marriage BJ, Oliver JS, et al. “Similar to Those Who Are Breastfed, Infants Fed a Formula Containing 2’-Fucosyllactose Have Lower Inflammatory Cytokines in a Randomized Controlled Trial” J Nutr. 2016;146(12):25592566 11. Puccio G, Alliet P, Cajozzo C, et al. “Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity: A Randomized Multicenter Trial” J Pediatr Gastroenterol Nutr. 2017;64(4):624-631 doi: 10.1097/ MPG.0000000000001520

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2’-FL S P ONS OR ’ S C ONT E NT

BASF IN THE FIELD: HUMAN MILK OLIGOSACCHARIDES BASF 2’-FL for infant health, gut health, adult health, and more.

nfant nutrition is the cornerstone to optimal child development, and breastfeeding plays a major role in that because of breast milk’s robust nutritional profile and wide acceptance as the gold stand. When compared with infant milk formula, breastfeeding positively affects growth patterns, nutritional status, immune health, and long-term developmental outcomes. As such, a lot of research and innovation in product development has been focused on narrowing the nutritional gap between human milk and infant milk formula, which is mostly based on cow milk. The key differentiating factor between human and bovine milk is human milk oligosaccharides (HMO)—complex carbohydrates that make up the third largest solid component of human milk. Human milk has 300-times the amount of oligosaccharides as cow milk. More than 200 HMOs have been identified in human milk, the most abundant being 2’-Fucosyllactose (2’-FL), comprising 20 – 30% of the total HMO content. 14

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Benefits of 2’-FL 2’-FL has been the subject of several studies. It has been shown to support gut health by stimulating the growth of healthy bacteria (1,2) and reducing the occurrence of diarrhea (3); immune function (4); and brain development and cognition. (5) In 2019, BASF launched PREBILAC™ 2’-FL for the infant-nutrition market. The ingredient was developed in-house—from strain development to downstream processing using a fermentation strain designed for efficient large-scale production. BASF plans to use its research platforms for biocatalytics and novel-strain development technologies to further progress within the category, as well as partner with selected customers for clinical trials. The selection of stable fermentation strains enables consistent quality of PREBILAC™ 2’-FL, without the use of antibiotics during production.

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Gut Health in Adolescents and Adults To further these efforts, BASF and Glycosyn, a biotechnology company that develops HMO products, partnered to further develop and commercialize HMOs for use in dietary supplements, functional nutrition, and medical foods; improve gastrointestinal health in adolescents and adults, including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD); and broaden the applications of HMO for further health conditions. Emerging scientific evidence shows that 2’-FL supports the development and maintenance of a healthy gut microbiome and immune system. Based on its prebiotic functions and the ability to inhibit pathogen adhesion and modulate immune functions, 2’-FL is a promising agent for digestive health across various age groups beyond infancy. Through partnership, R&D, and technology, the HMO category will continue to expand and new ways to address infant and adult nutrition will be developed.

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References: 1. Ward RE, Ninonuevo M, Mills DA, Lebrilla CB, German JB. “In vitro fermentation of breast milk oligosaccharides by Bifidobacterium infantis and Lactobacillus gasseri” Appl Environ Microbiol. 2006;72:4497–9 2. Ben XM, Li J, Feng ZT, Shi SY, Lu YD, Chen R, et al. “Low level of galacto-oligosaccharide in infant formula stimulates growth of intestinal Bifidobacteria and Lactobacilli” World J Gastroenterol. 2008;14:6564–8 3. Morrow AL, Ruiz-Palacios GM, Altaye M. “Human milk oligosaccharides are associated with protection against diarrhea in breast-fed infants” J Pediatr. 2004;145(3):297-303 4. Goehring KC, Marriage BJ, Oliver JS, et al. “Similar to Those Who Are Breastfed, Infants Fed a Formula Containing 2’-Fucosyllactose Have Lower Inflammatory Cytokines in a Randomized Controlled Trial” J Nutr. 2016;146(12):2559-2566 5. Pei JJ, Tang J. “A review on the relationship between breast milk nutrients and brain development in preterm infants” Zhonggu o Dang Dai Er Ke Za Zhi 2019;21(6):607-612