Although rotavirus vaccination programs are now widespread, rotavirus-associated diarrhea persists in many developing countries and rotavirus continues to be a major viral pathogen in areas where vaccination is not common. The WHO rotavirus surveillance program recently reported that 46% of infants under the age of 12 months who were hospitalized with diarrhea tested positive for rotavirus in countries where children are not vaccinated compared to 17% in countries where vaccination is routine. Therefore, it is important to identify additional methods for preventing or reducing the impact of rotavirus infection.
Prior research has clearly demonstrated that human milk oligosaccharides (HMOs) have antimicrobial and immunomodulatory actions, however little attention has been paid to the potential role of complex oligosaccharides in the immune response to rotavirus infection. New research undertaken at the University of Illinois set out to investigate the effects of HMOs and prebiotic oligosaccharides on immune cell populations from non-infected and rotavirus-infected pigs, in a first step towards informing the design of improved human infant formulas. The research team believed that dietary HMOs would modulate systemic and gastrointestinal immunity, following on from earlier research which showed that oligosaccharides contribute to the reduced duration of rotavirus-induced diarrhea in pigs.
During the research, colostrum-deprived newborn pigs were divided into three groups and fed either HMO-rich formula, formula with long- and short-chain oligosaccharides (prebiotics) or a regular control formula. On day 10, half the pigs were infected with a porcine rotavirus strain and monitored for immunity.
The results showed that dietary HMOs were considerably more effective than prebiotics in altering systemic and gastrointestinal immune cells in pigs. The HMO-fed pigs had nearly 50% more infection-fighting cells, 36% more mesenteric lymph node ( MLN ) effector memory T cells and five times more Peripheral blood mononuclear cells (PBMC) than regular formula-fed pigs. The pigs fed prebiotics showed intermediate results. HMO-induced changes in MLN cell populations were seen by the research team as particularly important in the resolution of clinical signs of rotavirus infection. The MLN is a key site of the immune response to rotavirus. If an increase in memory effector T cells occurs in the MLN before infection, pigs fed HMOs could respond to rotavirus infection and other immunologic challenges faster than the other formula-fed pigs.
The University of Illinois research team concluded that HMOs were more effective than prebiotics in altering systemic and gastrointestinal immune cells: these altered immune cell populations may mediate the effects of dietary HMOs on rotavirus infection susceptibility. While this was a limited study, it is among the first to assess the effects of a combination of dietary HMOs on cellular immunity in the context of pathogenic challenge in a large animal model. It is the first step toward understanding the in vivo bioactivities of HMOs. The positive results of the study point to the need for future investigations into how HMO-associated changes in the microbiome regulate neonatal cellular immune function.
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