Modulation of the Immune System by Human Milk and Infant Formula Containing Nucleotides

Pickering, Larry K.; Granoff, Dan M.; Erickson, Julie Reed; Masor, Marc L.; Cordle, Christopher T.; Schaller, Joseph; Winship, Timothy R.; Paule, Charles L.; Hilty, Milo D.

doi:10.1542/peds.101.2.242

Cited by 256 publications

(168 citation statements)

References 47 publications

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“…These results suggested that nucleotides could act as prebiotics favouring the proliferation of the beneficial flora and inhibiting that of potential pathogens. These results support clinical findings showing a low incidence of acute diarrhoea in infants fed nucleotide supplemented formula in developing (Brunser et al, 1994) and developed countries (Pickering et al, 1998).…”

Section: Dietary Nucleotides and Defence Against Infectionsupporting

confidence: 89%

“…Refeeding after malnutrition did not produce any significant changes either in serum total and specific immunoglobulins against a-casein and b-lactoglobulin or in saliva IgA levels (Martínez-Augustín et al, 1997). Finally, a recent study has also shown that dietary nucleotides may modulate the immune response in normal infants, enhancing the production of specific IgG against low response antigens, namely H. influenzae type b, a bacterium responsible for meningitis episodes in early infancy (Pickering et al, 1998).…”

Section: Modulation Of Immunoglobulin Production By Nucleotidesmentioning

confidence: 99%

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Modulation of the immune response mediated by dietary nucleotides

2002

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Dietary nucleotides have been reportedly beneficial, especially for infants, since they positively influence lipid metabolism, immunity, and tissue growth, development and repair. Rapidly proliferating tissues, such as the immune system or the intestine are not able to fulfil the needs of cell nucleotides exclusively by de novo synthesis and they preferentially utilize the salvage pathway recovering nucleosides and nucleobases from blood and diet. In the present review we describe the modulatory effect of dietary nucleotides on the immune system together with some of their effects on gut-associated lymphoid tissue. Dietary nucleotides influence lymphocyte maturation, activation and proliferation. Likewise, they affect the lymphocyte subset populations in both the small intestine and blood. Moreover, they are involved in enhancing macrophage phagocytosis and delayed hypersensitivity as well as allograft and tumour responses. In addition, they contribute to the immunoglobulin response in early life, having a positive effect on infection. In fact the incidence and duration of acute diarrhoea is lower in infants fed supplemented-nucleotide formulas. The molecular mechanisms by which dietary nucleotides modulate the immune system are practically unknown. Dietary nucleotides have been shown to enhance the production and the genetic expression of IL-6 and IL-8 by foetal small intestinal explants. Dietary nucleotides may influence protein biosynthesis as well as signal membrane transduction mediated by the interaction of exogenous nucleosides and their receptors may also contribute to modulate the expression of a number of genes, some of which can directly affect the levels of intestinal cytokines.

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Section: Dietary Nucleotides and Defence Against Infectionsupporting

confidence: 89%

Section: Modulation Of Immunoglobulin Production By Nucleotidesmentioning

confidence: 99%

Modulation of the immune response mediated by dietary nucleotides

2002

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“…The results from these studies are controversial. However, a well-executed randomized trial was recently reported, showing that breastfed infants exhibit enhanced specific antibody titre to some, but not all, vaccines (Pickering et al 1998). Very little work has been carried out on the cell-mediated immune response in breast-fed v. bottle-fed infants.…”

Section: Maternal Milk and Immune Modulationmentioning

confidence: 99%

Early nutrition and the development of immune function in the neonate

Kelly¹,

Coutts²

2000

Proc. Nutr. Soc.

175

119

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The present review will concentrate on the development of the gut-associated lymphoid tissue and the role of early nutrition in promoting immune function. The intestine is the largest immune organ in the body, and as such is the location for the majority of lymphocytes and other immune effector cells. The intestine is exposed to vast quantities of dietary and microbial antigens, and is the most common portal of entry for pathogens, some of which are potentially lethal. The development of normal immune function of the intestine is therefore vital for survival, and is dependent on appropriate antigen exposure and processing, and also an intact intestinal barrier. In early life innate mechanisms of defence are probably more important than active or adaptive mechanisms in responding to an infectious challenge, since the healthy neonate is immunologically naïve (has not seen antigen) and has not acquired immunological memory. During this period maternal colostrum and milk can significantly augment resistance to enteric infections. The mechanisms of enhancing disease resistance are thought to be passive, involving a direct supply of anti-microbial factors, and active, by promoting the development of specific immune function. A tolerance response to dietary and non-invasive antigens is generally induced in the gut. However, it must also be able to mount an adequate immune response to ensure clearance of foreign antigens. It is now recognized that regulation of tolerance and active immune responses is critical to health, and failure to regulate these responses can lead to recurrent infections, inflammatory diseases and allergies. The education of the immune system in early life is thought to be critical in minimizing the occurrence of these immune-based disorders. During this phase of development maternal milk provides signals to the immune system that generate appropriate response and memory. One factor that has been proposed to contribute to the increase in the incidence of immune-based disorders, e.g. atopic diseases in Western countries, is thought to be the increased prevalence of formula-feeding.

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“…The primary justification for these additions was evidence in animals and humans that dietary NT enhance development of the gastrointestinal and immune systems. 1,2 A lower incidence of diarrhea, 3-5 enhanced response to vaccination, 4,6,22 and effects on natural killer cell activity 7 and immune cell subset distribution 8 have been reported in term infants. We are aware of only one published study reporting dietary NT effects in preterm infants: serum concentrations of immunoglobulin G to b-lactoglobulin were significantly greater in preterm infants fed NT-supplemented formula for 30 days.…”

mentioning

confidence: 99%

“…Three randomized, well-controlled, multi-center studies in term infants enrolled a total of more than 300 infants into each of the control and study groups. 4,6,21 Two of the studies reported that dietary NT supplementation enhanced infants' responses to vaccination, 4,6 while one reported that immune cell profiles of infants fed NT-supplemented formula tended to be more like those fed human milk. 8 A more recent study reported that infants fed NTsupplemented formula had significantly higher responses to tetanus toxoid.…”

mentioning

confidence: 99%

Dietary nucleotides and preterm infant nutrition

Carver

Stromquist

2006

J Perinatol

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Nucleotides (NT) have been added to formulas for term infants in the US since the mid-1980s, and to formulas for preterm infants since 2002. The primary justification for these additions was evidence in animals and humans that dietary NT enhance development of the gastrointestinal and immune systems. 1,2 A lower incidence of diarrhea, 3-5 enhanced response to vaccination, 4,6,22 and effects on natural killer cell activity 7 and immune cell subset distribution 8 have been reported in term infants. We are aware of only one published study reporting dietary NT effects in preterm infants: serum concentrations of immunoglobulin G to b-lactoglobulin were significantly greater in preterm infants fed NT-supplemented formula for 30 days. 9 In the early 1990's, we participated in a multi-center, randomized clinical trial to investigate dietary NT effects in very low birth weight preterm infants. There was no significant effect of NT supplementation on indices of immune function -the primary outcome measure. At one of the three sites, there was a greater incidence of necrotizing enterocolitis (NEC) among infants fed the NT-supplemented formula (five of 40 infants (12.5%) in the supplemented group versus 0 of 44 infants in the unsupplemented group). A direct causal relationship between the NT-supplemented study formula and the development of NEC could not be established, since the incidence of NEC in the study group was equivalent to the incidence among similar non-study infants admitted to our neonatal intensive care units at that time. The results of this study were not submitted for publication due to several significant methodological issues related to the study design.Other reports published since the completion of the study have renewed our interest in the role of dietary NT in gastrointestinal function. We and others have reported that dietary NTsupplemented formula was associated with sustained postprandial increases in superior mesenteric artery blood flow velocity in preterm 10 and term infants. 11,12 The clinical significance of dietary NT effects on splanchnic blood flow is unclear, since postprandial blood flow velocities were more similar between infants fed human milk and infants fed formula with no added NT, than they were between infants fed human milk and infants fed formula with added NT. However, we speculate that NT effects on the gastrointestinal and immune systems may relate to NT effects on splanchnic blood flow, perhaps via effects on gut-associated lymphoid tissues. Additional studies are needed to clarify the relationship between NT-related effects on intestinal blood flow and gastrointestinal function. Studies in animals provide interesting yet conflicting observations. In rodents, dietary NT reportedly protect against and accelerate healing following bowel injury, 1,13-17 and accelerate changes in intestinal lymphocyte maturation. 18 However, Matheson et al. 19 reported that an immune-enhancing diet containing fish oil, arginine and NT increased ileal blood flow and proinflammatory cytokines in...

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Modulation of the Immune System by Human Milk and Infant Formula Containing Nucleotides

Abstract: Infant formula fortified with nucleotides enhanced H influenzae type b and diphtheria humoral antibody responses. Feeding human milk enhanced antibody responses to OPV. Dietary factors play a role in the antibody response of infants to immunization.

Cited by 256 publications

References 47 publications

Modulation of the immune response mediated by dietary nucleotides

Modulation of the immune response mediated by dietary nucleotides

Early nutrition and the development of immune function in the neonate

Dietary nucleotides and preterm infant nutrition

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