Four types of oligosaccharides found in milk inhibited the infectivity of the two major strains of human rotavirus when tested in the epithelial kidney cells of African green monkeys, found researchers from Bayer College of Medicine, Houston.
Compared with prebiotic-free control samples, “all oligosaccharides substantially reduced the infectivity of both human rotavirus strains in vitro; however, virus strain–specific differences in effects were observed,” wrote lead researcher Professor Sasirekha Ramani.
It was also notable that the oligosaccharides exerted their effect directly on the virus rather than on the cells.
“Milk oligosaccharides reduce the infectivity of human rotaviruses in MA104 cells, primarily through an effect on the virus,” wrote the researchers.
The human rotavirus is the leading causes of severe dehydrating gastroenteritis in infants and toddlers and is thought to cause over 200,000 deaths annually. Breast milk contains Human Milk Oligosaccharides (HMOs), which are known to provide a degree of protection against rotavirus in breast-fed babies.
The findings of this study are important because they suggest that addition of these prebiotic compounds to infant formula may offer similar protection to infants who are not breast-fed.
“Although breastfed infants are directly protected, the addition of specific oligosaccharides to infant formula may confer these benefits to formula-fed infants,” explained the researchers.
The researchers induced two strains of human rotavirus infections (G1P and G2P) in African green monkey kidney epithelial (MA104) cells. The cells were exposed to four different milk oligosaccharides dissolved in a culture medium (or an oligosaccharide-free medium as control). The oligosaccharides used were 2′-fucosyllactose (2′FL), 3′-sialyllactose (3′SL), 6′-sialyllactose (6′SL), and galacto-oligosaccharides (GOS).
Oligosaccharide concentrations were either 2.5 milligrams/ millilitre (mg/ml) or 5 mg/ml. The higher concentrations were more effective at reducing rotavirus infectivity.
The oligosaccharide 2’FL, when added after infection, induced the maximum reduction (62%) in G1P infectivity. For G2P, the largest reduction in infectivity (73%) was achieved by adding a mixture of 3’SL and 6’SL during infection. The proportions of the two prebiotics used to induce this optimum reduction was the same ratio as is present in breast milk.
Although the oligosaccharides appeared to exert their anti-infective benefits by direct action on the virus, the exact mechanism is not fully understood. Additionally, although the prebiotics inhibited the rotavirus infectivity, they did not block it entirely.
The researchers speculated the effect of the oligosaccharides in humans might be more pronounced than in vitro.
“It is possible that the direct effects of oligosaccharides on the virus, together with other components of intestinal immunity and innate defences, would result in greater inhibition of infectivity,” they suggested.
Further testing of milk oligosaccharides in human intestinal epithelial cells would be the next step in determining whether there are additional benefits of milk oligosaccharides on rotavirus infectivity.
Despite the preliminary nature of the study findings, the researchers emphasised the potential of adding milk oligosaccharides to formula.
“Although further optimization of effective concentrations and testing in preclinical models and human studies is required, the reduction of rotavirus infectivity by milk oligosaccharides provides an added incentive for the addition of specific oligosaccharides to infant formula and could confer additional benefits to formula-fed infants,” they concluded.
Source: The Journal of Nutrition
Volume 147, issue 9, pp1709-1714. DOI: 10.3945/jn.116.246090
“Milk Oligosaccharides Inhibit Human Rotavirus Infectivity in MA104 Cells”
Authors: Daniel R Laucirica, Vassilis Triantis, Ruud Schoemaker, Mary K Estes, and Sasirekha Ramani