Sugar-coated Surprise: Diversity of Seal Milk Oligosaccharides

Written by: Lauren Milligan Newmark, Ph.D. | Issue # 131 | 2026

Grey seals (Halichoerus grypus) produce milk with an extreme macronutrient composition:  nearly 60% fat and less than 1% carbohydrate [1]. With a consistency more like toothpaste than water, their high-fat milk fuels the rapid growth of grey seal pups, who gain an average of two kilograms of body weight per day, 75% of which is fat [2, 3]. Weaned at only 15 to 20 days old, grey seal pups depend on this intense fat accumulation to survive their cold, aquatic environment. Lactose, the primary carbohydrate in most mammalian milks, draws water into the mammary gland through osmotic pressure and results in more dilute milks, like those of humans and other primates [4]. If you are trying to quickly fatten up a newborn seal pup, more milk sugar isn’t the way to do it.

But don’t let sugar’s low volume or lack of contribution to growth fool you into thinking that the carbohydrates in grey seal milk aren’t critical for the infant seal’s survival. The results of a new study [5] demonstrate that within that one percent carbohydrate fraction is one of the most diverse profiles of oligosaccharides of any mammalian milk studied to date, approaching human milk in complexity. The very same evolutionary pressures that selected for high milk fat composition in grey seals—rapid growth in a cold, aquatic environment—may have also selected for a highly diverse and unique milk oligosaccharide profile [5]. 

Secret Agent Sugars

Oligosaccharides are typically chains of three to twenty single sugar molecules (monosaccharides) linked to a lactose molecule. When lactose is delivered in milk on its own, it is broken down into glucose and galactose by the intestinal enzyme lactase. But when lactose is hitched to additional saccharides, the resulting oligosaccharide is indigestible. Whereas undigested lactose can result in gastrointestinal issues, undigested milk oligosaccharides are associated with positive health outcomes.  

When they arrive in the infant’s large intestine, some milk oligosaccharides act as prebiotics, feeding healthy bacteria (probiotics) and positively shaping the make-up of the infant’s gut microbiome and the development of the infant’s immune system [5, 6]. Some oligosaccharides are molecular look-alikes for sugars found on the surface of gut epithelial cells and can act as soluble decoy receptors for pathogens. Instead of a virus or bacteria binding to the infant’s gut and causing infection, these pathogens instead bind to oligosaccharides and are flushed from the gastrointestinal tract [6].  Their similar molecular make-up also allows oligosaccharides to engage in competitive inhibition with pathogens. Oligosaccharides can bind directly to receptors on cells lining the infant’s gut that are also docking sites for pathogens. By occupying these docks, pathogens can’t get a foothold and cause infection [6]. 

Carbohydrate Kaleidoscope

Because milk oligosaccharides vary in the number, type, and order of saccharide molecules, there is potential for enormous structural diversity. There are currently just over 650 known oligosaccharide structures across all mammalian milks [5]. Diversity in structure is one of milk oligosaccharides’ superpowers—it allows them to mimic the great diversity of intestinal pathogens [5,6]. 

Human milk has the most structurally diverse oligosaccharide profile with 380 different oligosaccharides identified to date; just over 200 are unique to humans [5,6]. This greatly exceeds the structural diversity seen in milks of domesticated mammals, such as cows and goats, leading to the hypothesis that human milk is uniquely saturated in a diverse milk oligosaccharide profile as the result of selective pressures for enhanced immune protection of human infants [5]. 

One problem with this hypothesis is the small sample size of non-human mammals with which it has been tested. There is a relationship between the number of identified oligosaccharide structures and published studies; understudied mammals appear to have less diversity, whereas well-studied mammals (i.e., humans) are extremely structurally diverse [5]. To determine whether humans are truly unique, and to better understand the types of selective pressures that might favor a diverse milk glycome, milk researchers need to look beyond domesticated mammals as their comparative species.

Large, Diverse, and Complex

One research team looked well beyond their local farm and all the way to the Isle of Man in the North Sea, just off the coast of Scotland [5]. Using milk samples collected from a previous project, the Swedish-led team painstakingly mapped the species diversity of milk oligosaccharides from five Atlantic grey seal mothers at four time points across lactation (days 2, 7, 13 and either day 17,18, or 19). Grey seals were of interest because of their extremely short lactation period in an equally extreme environment,  including high pathogen exposure [5]. These factors may favor a diverse milk oligosaccharide profile to provide protection during a very short infancy. 

From these 20 samples, the researchers measured and quantified 332 unique milk oligosaccharides and structurally characterized 240 of them, placing grey seals just behind humans in most characterized milk oligosaccharides [5]. Even more intriguing was the finding that 166 of the 240 (69%) characterized structures had never been documented in any other mammalian milk [5]. 

The study authors argued that seal milk could even surpass human milk in diversity with additional sample analysis. Because not every milk sample contains the total diversity in milk oligosaccharides for the species, the larger the sample size, the greater chances of identifying a higher number of oligosaccharide structures. If researchers could identify this much diversity and complexity from 5 seal mothers, what might they find if they had milk from 10 more seal mothers, or hundreds more like we have for humans?

There is one category where seal milk is the clear frontrunner—longest oligosaccharide chain. Whereas the longest oligosaccharide in human milk has 18 monosaccharides, grey seal milk had “giant” oligosaccharides, with the longest containing 28 monosaccharides. Indeed, this newly identified molecule holds the record as the largest mammalian non-polysaccharide glycan of any type [5]. Giant oligosaccharides may be a shared trait of Phocid seals as oligosaccharides of 21 monosaccharides in length have been identified in milk from both hooded and bearded seals. 

Functionally speaking, these giant milk oligosaccharides could act as soluble receptor decoys or signaling molecules [5]. The function of an oligosaccharide derives from its structure—determining which types of molecules are on the front or back end of the oligosaccharide chain (is it a sulfate group? A fucose sugar? A sialic acid?) can provide clues as to what that oligosaccharide may do in the infant’s gut. For example, sulfated milk oligosaccharides are believed to support the infant’s mucosal layer by mimicking gut polysaccharides and keeping pathogens from adhering to the gut surface [5]. Sulfation was a common modification of oligosaccharides in grey seal milk—they identified 53 sulfated structures, 48 of which were newly identified—but is less common in humans [5].

The researchers also identified oligosaccharides that are believed to have anti-biofilm activities. Biofilm is like a bacteria’s sticky protective shield. Many of the identified oligosaccharides from grey seal milk have structures that suggest they can either keep bacteria from forming these protective shields or work with other anti-microbial molecules to break down these sticky barriers, making bacteria more vulnerable to destruction [5]. 

Time-Lapse Lactation

With a lactation period measured in days rather than years, the research team was able to analyze samples from early, middle, and late lactation for grey seals. Using statistical analyses, the researchers found that the milk samples clustered by their day of collection, demonstrating that milk oligosaccharide profiles change over time in similar ways across mothers [5]. They identified three temporally important clusters: oligosaccharides exclusively expressed in early milk, a cluster representing oligosaccharides whose expression was stable across lactation, and finally a late oligosaccharide profile that was distinct in composition from early milk [5]. Because these three temporal clusters relate to different functional groups of oligosaccharides, the researchers believe that these milk oligosaccharides evolved to meet the changing needs of the rapidly growing pup [5]. 

Oligosaccharides also became more diverse as the nursing period progressed [5]. Weaning is extremely abrupt in grey seals; mothers stop nursing and leave the weaned infant on land or ice sheets to provide for themselves. These pups are vulnerable as their own immune system is still immature. Selection may have favored a diverse oligosaccharide profile just prior to weaning to ensure that weaned seal pups had established a healthy gut microbiome and were well protected against various pathogens once they were no longer receiving immune components from milk. 

Milk’s Molecular Archives

On paper, grey seal milk’s scarce carbohydrate fraction suggests sugars play little role in a seal pup’s growth and development. But a more in depth analysis revealed a highly complex oligosaccharide profile that changed with the needs of the growing infant, potentially improving survival by positively influencing the composition of the gut microbiome and helping the seal’s immune system ward off pathogens. 

The research team eloquently describe milk oligosaccharides as “exquisite repositories of evolutionary information” because they reflect adaptations to “specific environmental niches” [5]. Humans were thought to be unique in having such a complex oligosaccharide profile, but the wide variety in ecological habitats and reproductive strategies across mammal species suggests that oligosaccharide diversity could be found in many branches of the mammalian family tree. 

Further research into these evolutionary milk archives not only helps increase our understanding of how milk has been evolutionarily fine-tuned to meet the needs of each mammal species but also shapes our understanding of the evolution of human milk composition. The more we understand which features are shared across mammalian species—either through shared genetic ancestry or shared selective pressures—the better our understanding of what human infants need for optimal growth and development.

References

1. Oftedal OT, Iverson SJ. 1995. In: Jensen RG, editor. Handbook of Milk Composition. San Diego: Academic Press; 1995. P. 749-788
2. Watson DG, Pomeroy PP, Kennedy MW. Atlantic grey seal milk shows continuous changes in key metabolites and indicators of metabolic transition in pups from birth to weaning. Frontiers in Marine Science. 2021 Jan 11; 7:596904.
3. Lydersen C, Hammill MO, Kovacs KM. Milk intake, growth and energy consumption in pups of ice-breeding grey seals (Halichoerus grypus) from the Gulf of St. Lawrence, Canada. Journal of Comparative Physiology B. 1995 Mar;164(8):585-92.
4. Hinde K & Milligan LA. 2011. Primate milk: proximate mechanisms and ultimate perspectives. Evol Anthropology 20: 9-23.
5. Jin C, Lundstrøm J, Cori CR, Guu SY, Bennett AR, Dannborg M, Pomeroy PP, Kennedy MW, Bengtsson-Palme J, Hevey R, Khoo KH. Seal milk oligosaccharides rival human milk complexity and exhibit functional dynamics during lactation. Nature Communications. 2025 Nov 25;16(1):10067.
6. German JB, Freeman SL, Lebrilla CB, Mills DA. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Personalized nutrition for the diverse needs of infants and children. Nestle Nutr Workshop Ser Pediatr Program 2008; 62: 205-22.

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