Paul S. Noakes

Atopy risk in infants and children in relation to early exposure to fish, oily fish, or long-chain omega-3 fatty acids: a systematic review.

There are two main families of polyunsaturated fatty acids (PUFAs), the n−6 and the n−3 families. It has been suggested that there is a causal relationship between n−6 PUFA intake and allergic disease, and there are biologically plausible mechanisms, involving eicosanoid mediators of the n−6 PUFA arachidonic acid, that could explain this. Fish and fish oils are sources of long-chain n−3 PUFAs and these fatty acids act to oppose the actions of n−6 PUFAs. Thus, it is considered that n−3 PUFAs will protect against atopic sensitization and against the clinical manifestations of atopy. Evidence to examine this has been acquired from epidemiologic studies investigating associations between fish intake in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children and from intervention studies with fish oil supplements in pregnancy, lactation, infancy, and childhood, and atopic outcomes in infants and children. All five epidemiological studies investigating the effect of maternal fish intake during pregnancy on atopic or allergic outcomes in infants/children of those pregnancies concluded protective associations. One study investigating the effects of maternal fish intake during lactation did not observe any significant associations. The evidence from epidemiological studies investigating the effects of fish intake during infancy and childhood on atopic outcomes in those infants or children is inconsistent, although the majority of the studies (nine of 14) showed a protective effect of fish intake during infancy or childhood on atopic outcomes in those infants/children. Fish oil supplementation during pregnancy and lactation or during infancy or childhood results in a higher n−3 PUFA status in the infants or children. Fish oil provision to pregnant women is associated with immunologic changes in cord blood and such changes may persist. Studies performed to date indicate that provision of fish oil during pregnancy may reduce sensitization to common food allergens and reduce prevalence and severity of atopic dermatitis in the first year of life, with a possible persistence until adolescence with a reduction in eczema, hay fever, and asthma. Fish oil provision to infants or children may be associated with immunologic changes in the blood but it is not clear if these are of clinical significance and whether they persist. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, but this benefit may not persist as other factors come into play. It is not clear whether fish oil can be used to treat children with asthma as the two studies conducted to date give divergent results. Further studies of increased long-chain n−3 PUFA provision in during pregnancy, lactation, and infancy are needed to more clearly identify the immunologic and clinical effects in infants and children and to identify protective and therapeutic effects and their persistence.

Is there a role for fatty acids in early life programming of the immune system

There may be a causal relationship between n-6 PUFA intake and allergic disease and there are biologically plausible mechanisms, involving eicosanoid mediators of the n-6 PUFA arachidonic acid, that could explain this. There is some evidence that high linoleic acid intake is linked with increased risk of atopic sensitisation and allergic manifestations. Fish and fish oils are sources of long-chain n-3 PUFA and these fatty acids act to oppose the actions of n-6 PUFA. It is considered that n-3 PUFA will protect against atopic sensitisation and against the clinical manifestations of atopy. All five epidemiological studies investigating the effect of maternal fish intake during pregnancy on atopic or allergic outcomes in infants/children of those pregnancies concluded protective associations. Epidemiological studies investigating the effects of fish intake during infancy and childhood on atopic outcomes in those infants or children are inconsistent, although the majority of the studies (9/14) showed a protective effect of fish. Fish oil provision to pregnant women is associated with immunologic changes in cord blood. Provision of fish oil during pregnancy may reduce sensitisation to common food allergens and reduce the prevalence and severity of atopic dermatitis in the first year of life. This effect may persist until adolescence with a reduction in prevalence and/or severity of eczema, hayfever and asthma. Fish oil supplementation in infancy may decrease the risk of developing some manifestations of allergic disease, but whether this benefit persists as other factors come into play remains to be determined.

Increased intake of oily fish in pregnancy: effects on neonatal immune responses and on clinical outcomes in infants at 6 mo

BACKGROUND Long-chain n-3 PUFAs found in oily fish may have a role in lowering the risk of allergic disease. OBJECTIVE The objective was to assess whether an increased intake of oily fish in pregnancy modifies neonatal immune responses and early markers of atopy. DESIGN Women (n = 123) were randomly assigned to continue their habitual diet, which was low in oily fish, or to consume 2 portions of salmon per week (providing 3.45 g EPA plus DHA) from 20 wk gestation until delivery. In umbilical cord blood samples (n = 101), we measured n-3 fatty acids, IgE concentrations, and immunologic responses. Infants were clinically evaluated at age 6 mo (n = 86). RESULTS Cord blood mononuclear cell (CBMC) production of interleukin (IL)-2, IL-4, IL-5, IL-10, and tumor necrosis factor-α in response to phytohemagglutinin (PHA) and of IL-2 in response to Dermatophagoides pteronyssinus allergen 1 (Derp1) was lower in the salmon group (all P ≤ 0.03). In the subgroup of CBMCs in which an allergic phenotype was confirmed in the mother or father, IL-10 production in response to Toll-like receptor 2, 3, and 4 agonists, ovalbumin, salmon parvalbumin, or Derp1 and prostaglandin E(2) production in response to lipopolysaccharide or PHA was lower in the salmon group (all P ≤ 0.045). Total IgE at birth and total IgE, incidence and severity of atopic dermatitis, and skin-prick-test positivity at 6 mo of age were not different between the 2 groups. CONCLUSION Oily fish intervention in pregnancy modifies neonatal immune responses but may not affect markers of infant atopy assessed at 6 mo of age. This trial is registered at clinicaltrials.gov as NCT00801502.

Salmon Consumption during Pregnancy Alters Fatty Acid Composition and Secretory IgA Concentration in Human Breast Milk

Fish oil supplementation during pregnancy alters breast milk composition, but there is little information about the impact of oily fish consumption. We determined whether increased salmon consumption during pregnancy alters breast milk fatty acid composition and immune factors. Women (n = 123) who rarely ate oily fish were randomly assigned to consume their habitual diet or to consume 2 portions of farmed salmon per week from 20 wk of pregnancy until delivery. The salmon provided 3.45 g long-chain (LC) (n-3) PUFA/wk. Breast milk fatty acid composition and immune factors [soluble CD14, transforming growth factor-β (TGFβ)1, TGFβ2, and secretory IgA] were analyzed at 1, 5, 14, and 28 d postpartum (PP). Breast milk from the salmon group had higher proportions of EPA (80%), docosapentaenoic acid (30%), and DHA (90%) on d 5 PP compared with controls (P < 0.01). The LC (n-6) PUFA:LC (n-3) PUFA ratio was lower for the salmon group on all days of PP sampling (P ≤ 0.004), although individual (n-6) PUFA proportions, including arachidonic acid, did not differ. All breast milk immune factors decreased between d 1 and 28 PP (P < 0.001). Breast milk secretory IgA (sIgA) was lower in the salmon group (d 1-28 PP; P = 0.006). Salmon consumption during pregnancy, at the current recommended intakes, increases the LC (n-3) PUFA concentration of breast milk in early lactation, thus improving the supply of these important fatty acids to the breast-fed neonate. The consequence of the lower breast milk concentration of sIgA in the salmon group is not clear.

β2-1 Fructans have a bifidogenic effect in healthy middle-aged human subjects but do not alter immune responses examined in the absence of an in vivo immune challenge: results from a randomised controlled trial

β2-1 fructans are considered to be prebiotics. Current literature indicates that β2-1 fructans may modulate some aspects of immune function, improve the hosts ability to respond to certain intestinal infections, and modify some inflammatory outcomes in human subjects. However, there is a need to find out more about the modulation of immune markers by β2-1 fructans in humans. Healthy human subjects aged 45-65 years were randomly allocated to β2-1 fructans (Orafti® Synergy1; 8 g/d; n 22) or the digestible carbohydrate maltodextrin as placebo (n 21) for 4 weeks. Blood, saliva and faecal samples were collected at study entry and after 4 weeks. Immune parameters were measured using the blood and saliva samples and bifidobacteria were measured in the faecal samples. Faecal bifidobacteria numbers increased in the Orafti® Synergy1 group (P < 0·001) and were different at 4 weeks from numbers in the placebo group (P = 0·001). There was no significant effect of Orafti® Synergy1 on any of the immune parameters measured (blood immune cell subsets, total serum Ig, salivary IgA, neutrophil and monocyte phagocytosis of Escherichia coli and respiratory burst in response to E. coli or phorbol ester, natural killer cell activity, T cell activation and proliferation, production of six cytokines by T cells). It is concluded that, compared with maltodextrin, Orafti® Synergy1 has a bifidogenic effect in healthy middle-aged human subjects but does not alter immune responses examined in the absence of an in vivo immune challenge.

Short-term infusion of a fish oil-based lipid emulsion modulates fatty acid status, but not immune function or (anti)oxidant balance: a randomized cross-over study.

Eur J Clin Invest 2012; 42 (3): 290–302

Effect of salmon consumption during pregnancy on maternal and infant faecal microbiota, secretory IgA and calprotectin

The gut microbiota plays an important role in the development of the immune and gastrointestinal systems of infants. In the present study, we investigated whether increased salmon consumption during pregnancy, maternal weight gain during pregnancy or mode of infant feeding alter the markers of gut immune defence and inflammation. Women (n 123) who rarely ate oily fish were randomly assigned to continue consuming their habitual diet or to consume two 150 g portions of farmed salmon per week from 20 weeks of pregnancy to delivery. Faecal samples were collected from the mothers (n 75) at 38 weeks of gestation and from their infants (n 38) on days 7, 14, 28 and 84 post-partum. Fluorescence in situ hybridisation was used to determine faecal microbiota composition and ELISA to measure faecal secretory IgA (sIgA) and calprotectin concentrations. There was no effect of salmon consumption on maternal faecal microbiota or on maternal or infant faecal sIgA and calprotectin concentrations. The degree of weight gain influenced maternal faecal microbiota, and the mode of infant feeding influenced infant faecal microbiota. Faecal samples collected from infants in the salmon group tended to have lower bacterial counts of the Atopobium cluster compared with those collected from infants in the control group (P=0·097). This difference was significant in the formula-fed infants (P< 0·05), but not in the exclusively breast-fed infants. In conclusion, the impact of oily fish consumption during pregnancy on maternal and infant gut microbiota composition is limited, but significant differences are associated with maternal weight gain during pregnancy and mode of infant feeding.

β-Hydroxy-β-methylbutyrate modifies human peripheral blood mononuclear cell proliferation and cytokine production in vitro

OBJECTIVE The main objective was to investigate the potential immunomodulatory effects of β-hydroxy-β-methylbutyrate (HMB) in human cells. METHODS Peripheral blood mononuclear cells were isolated from the blood of eight volunteers and assayed for proliferation, cell cycle progression, surface expression of CD25, intracellular expression of pERK1/2, and cytokine production after in vitro exposure to a range of HMB concentrations (0.1 to 10 mM). RESULTS Above 1 mM, HMB decreased the extent of proliferation normally observed after stimulation by concanavalin A. The decrease was evident at 10 mM HMB, when the proliferation index was 50% reduced when compared with the absence of HMB. Cell cycle analysis demonstrated an increase in the proportion of cells at the G0-G1 phase at 10 mM HMB. CD25 and pERK1/2 expression were not related to the observed effect on proliferation. HMB affected the concentrations of all five cytokines measured following stimulation. Tumor necrosis factor-α concentration in the culture medium was reduced by ~35% at all HMB concentrations. Th1/Th2 cytokine production was modified toward a Th2 profile when HMB was at 1 or 10 mM. Thus, HMB at 10 mM impairs lymphocyte proliferation and progression through the cell cycle. The lowest concentration used here (0.1 mM) exerted some actions on cytokine production, including decreasing TNF-α production, but not on proliferation and cell cycle progression. CONCLUSION HMB may be a useful agent to consider for modulation of immune function in specific situations.

Plasma Inflammatory and Vascular Homeostasis Biomarkers Increase During Human Pregnancy but Are Not Affected by Oily Fish Intake

The Salmon in Pregnancy Study investigated whether the increased consumption of (n-3) long-chain PUFA (LC-PUFA) from farmed Atlantic salmon affects immune function during pregnancy and atopic disease in neonates compared with a habitual diet low in oily fish. In this context, because the ingestion of (n-3) LC-PUFA may lower the concentrations of inflammatory biomarkers, we investigated whether the consumption of oily fish affects the levels of inflammatory cytokines and vascular adhesion factors during pregnancy. Pregnant women (n = 123) were randomly assigned to continue their habitual diet (control group, n = 61), which was low in oily fish, or to consume two 150-g salmon portions/wk (salmon group, n = 62; providing 3.45 g EPA plus DHA) from 20 wk of gestation until delivery. Plasma inflammatory cytokines and vascular adhesion factors were measured in maternal plasma samples. Inflammatory biomarkers, including IL-8, hepatocyte growth factor, and monocyte chemotactic protein, increased over the course of pregnancy (P < 0.001), whereas plasma matrix metalloproteinase 9, IL-6, TNFα, and nerve growth factor concentrations were not affected. Vascular homeostasis biomarkers soluble E-selectin, soluble vascular adhesion molecule-1, soluble intercellular adhesion molecule (sICAM)-1, and total plasminogen activator inhibitor-1 increased as pregnancy progressed (P < 0.001). The plasma sICAM-1 concentration was greater in the control group than in the salmon group at wk 20 (baseline) and 38 (P = 0.007) but there was no group x time interaction, and when baseline concentration was used as a covariate, the groups did not differ (P = 0.69). The remaining biomarkers analyzed were similar in both groups. Therefore, although some inflammatory and vascular homeostasis biomarkers change during pregnancy, they are not affected by the increased intake of farmed salmon.

Documentation of functional and clinical effects of infant nutrition: setting the scene for COMMENT.

The Early Nutrition Academy and the Child Health Foundation, in collaboration with the Committee on Nutrition, European Society for Paediatric Gastroenterology, Hepatology and Nutrition, held a workshop in March 2011 to explore guidance on acquiring evidence on the effects of nutritional interventions in infants and young children. The four objectives were to (1) provide guidance on the quality and quantity of evidence needed to justify conclusions on functional and clinical effects of nutrition in infants and young children aged <3 years; (2) agree on a range of outcome measures relevant to nutrition trials in this age group for which agreed criteria are needed; (3) agree on an updated ‘core data set’ that should generally be recorded in nutrition trials in infants and young children, and (4) provide guidance on the use of surrogate markers in paediatric nutrition research. The participants discussed these objectives and agreed to set up six first working groups under the auspices of the Consensus Group on Outcome Measures Made in Paediatric Enteral Nutrition Clinical Trials (COMMENT). Five groups will aim to identify and define criteria for assessing key outcomes, i.e. growth, acute diarrhoea, atopic dermatitis and cows’ milk protein allergy, infections and ‘gut comfort’. The sixth group will review and update the ‘core data set’. The COMMENT Steering Committee will discuss and decide upon a method for reaching consensus which will be used by all working groups and plan to meet again within 2 years and to report and publish their conclusions.