Journal of Pediatric Gastroenterology & Nutrition:
Newburg, David S.
Department of Biology, Program in Glycobiology, Boston College, Boston, MA.
Address correspondence and reprint requests to David S. Newburg, PhD, Department of Biology, Program in Glycobiology, Boston College, 140 Commonwealth Ave, Boston, MA 02467 (e-mail: firstname.lastname@example.org).
Received 27 February, 2012
Accepted 28 February, 2012
The author reports no conflicts of interest.
See “Prevention of Rotavirus-induced Diarrhea by Preferential Secretion of IgA in Breast Milk via Maternal Administration of Lactobacillus gasseri SBT2055” by Kadooka et al on page 66.
Rotavirus infection has been a persistent cause of diarrhea in infants, both in developing and developed countries. For example, in a typical year before the widespread use of rotavirus vaccine, rotavirus infection in the United States was responsible for approximately 3.5 million cases of diarrhea, 50,000 hospitalizations, and 20 deaths in children younger than 5 years. Most children become infected with rotavirus, with the highest risk being from (6 months when circulating maternally acquired immune factors decline in infants) through 3 years of age. Although rotavirus vaccines can significantly reduce the incidence of severe rotavirus, issues of cost and infrastructure limit the utility of the vaccine in developing countries and also for some populations in developed countries, such as infants before immunization. Thus, alternative forms of rotavirus protection remain a public health priority.
Breast-fed infants have lower rates of diarrhea (1), including rotavirus-associated diarrhea (2). Protection against rotavirus by human milk includes its antirotavirus secretory immunoglobulin A (sIgA), which is present at varying levels in the milk of most mothers, and the human milk glycoprotein lactadherin, a constitutively produced glycoprotein that is present in all of the milk samples tested (3,4). In a general population, ingestion of probiotics reduces the risk of rotavirus (5). All of these forms of defense only confer partial protection from rotavirus infection. In a marginally nourished infant, a bout of infection, especially one that causes diarrhea, can start the infant on a spiral of malnutrition and disease that can result in death or suboptimal development in those who survive. Thus, finding an inexpensive, facile, and effective means to reduce rotavirus infection in high-risk infant populations remains an important research objective.
A study published in this issue of JPGN(6) uses a murine model of rotavirus infection in nursing pups to determine whether feeding killed Lactobacillus gasseri SBT2055 (LG2055) to adult females, or oral rotavirus immunization when they are gravid dams, or the combination of both treatments would reduce the incidence of rotavirus in their pups. Their nursing pups were inoculated with simian rotavirus SA-11 at 5 days of age: 90% of pups of control dams and of dams fed heat-killed LG2055 were infected with rotavirus. In contrast, only 35% of pups were infected if their dams had been immunized with rotavirus, but only 10% of pups were infected if their dams had been fed the heat-killed LG2055 and immunized with rotavirus. This highly protected group was receiving milk that contained more rotavirus-specific IgA. In Toll-like receptor 2 (TLR-2) and TLR-4 knockout mice, the isolated splenocytes of TLR-4 knockouts showed the same induction of IgA by the LG2055 probiotic as wild-type mice, whereas the TLR-2 knockout splenocytes did not show any induction of anti-rotavirus IgA.
Thus, prenatal treatment of the mother with a combination of probiotic and rotavirus immunization strongly protects her nursing offspring from rotavirus infection. This is mediated primarily through increased production of antirotavirus sIgA in her milk, which in turn depends upon Peyer patch monitoring of the contents of the intestinal lumen and TLR-2–dependent signaling in maternal immune cells. TLR-2-dependent signaling is amplified by the LG2055 probiotic.
These are exciting findings for several reasons. Clinically, treating the mother during pregnancy with a combination of probiotic feeding and immunization could lead to a more accessible and effective prophylactic for protecting highly vulnerable populations of infants, which could have a major effect on infant public health. Furthermore, these data may help provide a mechanism for protection against disease by probiotics, which may explain, in part, the inconsistent results among various studies on the ability of probiotics to protect against disease. If the major effect of probiotic treatment is to activate components of the mucosal immune system via an adjuvant-like activity, requiring stimulation by additional pathogen epitopes to mount a protective immune response, then different outcomes may be expected from different populations. From the standpoint of basic mucosal immunology research, this mechanism of maximum protection from a combination of probiotic treatment and mucosal immunization of the mother may have broad applicability for many other pathogens.
1. Morrow AL, Rangel JM. Human milk protection against infectious diarrhea: implications for prevention and clinical care. Semin Pediatr Infect Dis 2004; 15:221–228.
2. Plenge-Bonig A, Soto-Ramirez N, Karmaus W, et al. Breastfeeding protects against acute gastroenteritis due to rotavirus in infants. Eur J Pediatr 2010;169:1471–6.
3. Yolken RH, Peterson JA, Vonderfecht SL, et al. Human milk mucin inhibits rotavirus replication and prevents experimental gastroenteritis. J Clin Invest 1992; 90:1984–1991.
4. Newburg DS, Peterson JA, Ruiz-Palacios GM, et al. Role of human-milk lactadherin in protection against symptomatic rotavirus infection. Lancet 1998; 351:1160–1164.
5. Grandy G, Medina M, Soria R, et al. Probiotics in the treatment of acute rotavirus diarrhoea. A randomized, double-blind, controlled trial using two different probiotic preparations in Bolivian children. BMC Infect Dis 2010;10:253.
6. Kadooka Y, Tominari K, Sakai F, Yasui H. Prevention of rotavirus-induced diarrhea by preferential secretion of IgA in breast milk via maternal administration of Lactobacillus gasseri SBT2055. J Pediatr Gastroenterol Nutr 2012;55:68–73.