Study looks to aid formula makers with gut role in breast milk sugar uptake

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Researchers detail the role of transport proteins in nutrient uptake from breast milk, which the team say will aid formula makers to enrich their product with the sugars breast-fed children receive.

In a Danish-Japanese pact, the team identify and describe transport protein function that controls nutrient uptake from breastmilk to the Bifidoabcterium longum subsp. Infantis group in the child’s intestines.

In doing so, the findings will guide milk formula producers to “synthesise new sugar additives in a rational manner.

“This ensures children who drink infant formula receive similarly beneficial sugars as children who are breast-fed do,” according to study team member Maher Abou Hachem professor MSO at DTU - Technical University of Denmark.

HMO abundance

Apart from essential nutrients, infant diet or mothers’ milk contains human milk oligosaccharides (HMOs) which are the third most abundant component after lactose and lipids.

Twelve HMO structures account for over 90% of total HMOs by weight, with 2′-fucosyllactose (2′-FL) and 3-fucosyllactose (3-FL) being abundantly present.

The gut microbiota of breast-fed infants is dominated by bifidobacteria, where its abundance and prevalence in neonatal guts may be responsible for breaking down HMOs.

Despite the importance of oligosaccharide uptake in the gut ecosystem, insight into HMO uptake by bifidobacteria is limited.

Additionally, the mechanism of action underlying substrate preference and role of the transporters are largely unknown, although 2′-FL has been commercialised to improve infant formula.

Study details

The team from DTU and Kyoto University in Japan began by analysing faecal bacteria and mother’s milk from mother-infant pairs also employing a control group of human adults in Japan.

Meanwhile, the molecular description of the transport proteins and their HMO preferences was conducted in Denmark.

The team discovered a unique adaptation strategy of Bifidobacterium to HMOs, in which specific mutations enable a FL transporter to capture major fucosylated HMOs.

“The results obtained from faecal DNA and HMO consumption analyses and metagenomic data analysis reiterate HMOs as prime mediators in the dialog between humans and bifidobacteria,” the study says.

“Our findings highlight HMO-specific ABC transporters as a key fitness factor supporting the adaptation and dominance of bifidobacteria in the infant gut ecosystem.”

“It is crucial to establish the right gut microbiota early in the child's life. Conversely, factors that interfere with the development of the “right” microbiota are associated with life-long health disorders,” adds Dr Hachem.

“If we get the wrong organisms from early life and we get used to them and they are accepted as part of the microbiota, it will be very difficult to re-select the normal and beneficial bacteria afterwards.”

HMO influence on gut

To date, the impact of distinct sugars on the composition of the gut microbiota, and on infant health remains unclear.

Since many infants are raised on milk formula, intense research is ongoing in academia and industry to create an infant formula that compensates for the lack of HMOs in bovine milk as human HMOs are unique and are not present in animal milk.

The first generation of infant formula contained oligosaccharides from plants, e.g. galacto-oligosaccharides, which bore little resemblance to HMOs.

Currently, different firms now look to add synthetic sugars identical to authentic HMOs with these synthetised HMOs chosen based on how abundant they are in human milk.

However, little research exists as to how different HMO types influence the assembly of a healthy infant gut microbiota.

Source: Science Advances

Published online: DOI: 10.1126/sciadv.aaw7696

“Evolutionary adaptation in fucosyllactose uptake systems supports bifidobacteria-infant symbiosis.”

Authors: Mikiyasu Sakanaka et al