Rotavirus infection is reduced by breastfeeding in the first year of life (Panda S et al. Epidemiol Infect 2014). Human milk oligosaccharides (HMO) are thought to contribute to this protection, in part by binding to some rotavirus strains and interrupting virus binding to host cell glycoconjugate receptors.

The burden of rotavirus infection is significant. In 2008, based on global surveillance by the World Health Organization, rotavirus was estimated to cause 25 million outpatient visits, >2 million hospitalizations [http://www.who.int/biologicals/areas/vaccines/rotavirus/background/en/], and >453,000 deaths in children aged <5 years [http://www.who.int/immunization/monitoring_surveillance/burden/estimates/rotavirus/en/]. The greatest disease burden is in developing countries where the availability of rotavirus vaccines is limited and also seems to be less effective [Patel MM et al. Pediatr Infect Dis J 2011].

Sharon M. Donovan, PhD, RD, University of Illinois, Urbana, Illinois, USA, reviewed work by her group that tested the hypothesis that HMO, particularly those forms containing sialic acid, would decrease rotavirus infectivity by reducing binding and modulating gut microflora.

In a set of experiments to screen for rotavirus inhibitory activity in vitro, they found that sialyllactose-containing HMO and HMO isolated from preterm human milk (iHMO) inhibited infectivity and binding of sialic acid-dependent rotavirus at those concentrations present in human milk [Hester SN et al. Br J Nutr 2013]. They also found dose-dependent effects for binding and infectivity, which were more effective at a lower concentrations with 6′-sialyllactose than with 3′-sialyllactose; the groups believes that this distinction may be related to differences in the structures of the cellular binding sites. Dr. Donovan stated these results support sialic acid-dependent rotavirus binding by sialic acid-containing HMO as a primary mechanism of action.

Next, they studied the ability of HMO to inhibit rotavirus activity in situ using a piglet model. They showed that both sialic acid-containing HMO and a neutral HMO (lacto-N-neotetraose, LNnT) decreased rotavirus infectivity in isolated loops of intestine [Hester SN et al. Br J Nutr 2013], suggesting other possible mechanisms for the effect of HMO. Dr. Donovan noted that this study was also important for establishing a model that will allow for the screening of different HMO fractions, such as neutral and acidic, in order to determine which are most efficacious before testing in rotavirus infection studies in vivo, which would require large quantities of HMO.

Finally, Dr. Donovan showed the results of an in vivo study of rotavirus infection in colostrum-deprived piglets, which sought to determine the efficacy of formula supplemented with HMO (4 g/L), compared with formula alone. Dietary HMO reduced the duration of rotavirus infection by 30 hours, primarily by reducing the second wave of infection [Li M et al. ISME J 2014]. The effect of HMO on diarrhea and on the rates of initial and reinfection are detailed in Table 1. HMO increased serum rotavirus-specific immunoglobulin M (IgM) and increased interferon gamma (IFN-γ) and interleukin-10 (IL-10) levels in the ileum, which suggests the effects of HMO on both systemic and mucosal immunity, said Dr. Donovan. Furthermore, rotavirus infection significantly modified the microflora at the level of the phyla, family, and genus in the ascending colon, and that HMO promoted the growth of Lachnospiraceae.