An Unexpected Enzyme in a Baby's First Microbiome

An enzyme best known for recycling cell components in plants and animals turns out to help beneficial bacteria feed on breast milk in a baby's gut. The finding, from a team led by the University of Birmingham, adds a new piece to the puzzle of why breastfed infants develop the gut communities they do.

The enzyme, called PNGaseA, lets some Bifidobacterium bacteria pull sugars off short protein chains found in breast milk, the University of Birmingham said on Nov. 2. Those sugar-bearing fragments are present in human milk but not in infant formula.

"We were genuinely surprised to see that PNGaseA is used by gut bacteria," said lead researcher Lucy Crouch of the University of Birmingham.

The study was published Nov. 2 in Nature Communications. An earlier version was posted as a preprint on bioRxiv in 2025, before peer review.

This is laboratory research on an enzyme and its structure — it does not show that the enzyme changes infant health, and it does not change any feeding advice for parents.

Bifidobacterium and Breast Milk's Hidden Sugars

In breastfed infants, the gut is usually dominated by Bifidobacterium species. The Nature Communications paper notes this is at least partly because these bacteria can use human milk oligosaccharides, complex sugars in breast milk that babies cannot digest themselves.

Those sugars are not the only food source. Breast milk also contains many proteins decorated with sugar chains called N-glycans. Gut bacteria use enzymes to snip off those sugar chains and eat them. Until now, scientists knew little about how infant-associated bacteria handle these sugars when they are attached to short protein fragments, called N-glycopeptides.

The team searched the genomes of infant-associated Bifidobacterium species and found a rare PNGaseA-family enzyme in two strains of Bifidobacterium bifidum. They then studied the enzyme from an infant-derived strain, B. bifidum LMG13195, in detail.

Inside the Enzyme's Molecular Cradle

The researchers found that the enzyme strongly prefers sugar-bearing short protein fragments over whole proteins. Using structural biology, they showed why. The enzyme has a β-sheet "cradle" that grips the protein fragment and closes around it, lining up the attached sugar for removal.

Co-author Ramón Hurtado-Guerrero of the University of Zaragoza in Spain said the work reveals the first structure of a PNGase enzyme bound to an N-glycopeptide, Technology Networks reported. That structure shows how the enzyme recognizes both the sugar and the protein fragment attached to it.

There is also an ecological twist. The B. bifidum strain studied lacks some of the enzymes needed to fully break down the sugars it releases. According to the paper, those released sugars could become available to other gut microbes through cross-feeding. That suggests one bacterium's enzyme might help support a wider community.

The evidence has clear boundaries — the study characterized the enzyme in the lab using purified proteins and model substrates. It did not measure the enzyme's activity inside infants, and it did not compare health outcomes between babies. Only some Bifidobacterium strains carry the enzyme, so its overall importance in the infant gut remains unknown.

Implications for Future Infant Formula

The practical interest lies in formula. Because these sugar-bearing protein fragments are absent from formula, the researchers say understanding them could help engineer future formulas. Babies who cannot receive human milk might eventually benefit from new prebiotics, ingredients designed to feed beneficial bacteria.

"We know there are some aspects of breast milk that can't yet be truly synthetically replicated," Crouch said, according to News-Medical. She said characterizing the components that support healthy bacteria could help make formula more like human milk.

That goal is years away. Any new formula ingredient would need further research, safety testing, and regulatory review. Some formulas already include human milk oligosaccharides made in the lab, which shows how milk research can eventually reach store shelves, but this enzyme study is an early step.

The research also arrives amid growing interest in why some babies miss out on Bifidobacterium. Recent work reported by NutraIngredients found that up to one-third of infants lacked detectable levels of the bacteria despite breastfeeding. That suggests milk composition is only part of the story, alongside how bacteria are passed from mother to baby.

The finding fits a broader picture of breast milk as more than food for the baby alone. Breast milk carries sugars, proteins, antibodies, and even its own microbes, and many of its components appear to function partly as food for the infant's gut bacteria. A January 2026 Nature Communications study from the University of Chicago, for example, found that Bifidobacterium longum was common in breast milk samples and abundant in more than 98% of infants' gut microbiomes.

Bifidobacterium matters because of what it does once established. These bacteria ferment milk sugars into acids that lower the pH of the infant gut, which can make it harder for some harmful microbes to gain a foothold, and they are thought to help train the developing immune system. Scientists are still working out how much any single nutrient source, including the one this enzyme unlocks, contributes to that process.

For parents, nothing here calls for a change. Breastfeeding and infant formula both remain safe, appropriate ways to feed babies, and decisions about feeding, probiotics or supplements should be made with a pediatrician. No product on the market is based on this enzyme.

The bottom line is that scientists have identified a molecular tool some infant gut bacteria use to unlock a little-studied group of breast milk nutrients. The finding could guide future formula design, but its role in real infant health still needs to be tested.

What Readers Want to Know

What did researchers discover? An enzyme called PNGaseA helps some infant gut Bifidobacterium bacteria release and use sugars attached to short protein fragments in breast milk.

Why does Bifidobacterium dominate breastfed babies' guts? These bacteria are especially good at using breast milk sugars, including human milk oligosaccharides that babies cannot digest themselves.

Are these nutrients in formula? No. The sugar-bearing protein fragments the enzyme targets are found in human breast milk but not in infant formula.

Does this mean formula is unsafe? No. Formula remains a safe option. The study is lab research and does not change feeding guidance.

Could this lead to better formula? Possibly, in the long term. Researchers say the findings could help design new prebiotic ingredients, but that would require years of testing.

Was the study peer-reviewed? Yes. It was published in Nature Communications on Nov. 2, 2026, after appearing as a preprint in 2025.