Diet and Immune Function Childs, Caroline E; Calder, Philip C; Miles, Elizabeth A
Nutrients,
08/2019, Volume:
11, Issue:
8
Journal Article
Peer reviewed
Open access
A well-functioning immune system is critical for survival. The immune system must be constantly alert, monitoring for signs of invasion or danger. Cells of the immune system must be able to ...distinguish self from non-self and furthermore discriminate between non-self molecules which are harmful (e.g., those from pathogens) and innocuous non-self molecules (e.g., from food). This Special Issue of Nutrients explores the relationship between diet and nutrients and immune function. In this preface, we outline the key functions of the immune system, and how it interacts with nutrients across the life course, highlighting the work included within this Special Issue. This includes the role of macronutrients, micronutrients, and the gut microbiome in mediating immunological effects. Nutritional modulation of the immune system has applications within the clinical setting, but can also have a role in healthy populations, acting to reduce or delay the onset of immune-mediated chronic diseases. Ongoing research in this field will ultimately lead to a better understanding of the role of diet and nutrients in immune function and will facilitate the use of bespoke nutrition to improve human health.
The immune system is complex: it involves many cell types and numerous chemical mediators. An immature immune response increases susceptibility to infection, whilst imbalances amongst immune ...components leading to loss of tolerance can result in immune-mediated diseases including food allergies. Babies are born with an immature immune response. The immune system develops in early life and breast feeding promotes immune maturation and protects against infections and may protect against allergies. The long-chain polyunsaturated fatty acids (LCPUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) are considered to be important components of breast milk. AA, eicosapentaenoic acid (EPA) and DHA are also present in the membranes of cells of the immune system and act through multiple interacting mechanisms to influence immune function. The effects of AA and of mediators derived from AA are often different from the effects of the n-3 LCPUFAs (i.e., EPA and DHA) and of mediators derived from them. Studies of supplemental n-3 LCPUFAs in pregnant women show some effects on cord blood immune cells and their responses. These studies also demonstrate reduced sensitisation of infants to egg, reduced risk and severity of atopic dermatitis in the first year of life, and reduced persistent wheeze and asthma at ages 3 to 5 years, especially in children of mothers with low habitual intake of n-3 LCPUFAs. Immune markers in preterm and term infants fed formula with AA and DHA were similar to those in infants fed human milk, whereas those in infants fed formula without LCPUFAs were not. Infants who received formula plus LCPUFAs (both AA and DHA) showed a reduced risk of allergic disease and respiratory illness than infants who received standard formula. Studies in which infants received n-3 LCPUFAs report immune differences from controls that suggest better immune maturation and they show lower risk of allergic disease and respiratory illness over the first years of life. Taken together, these findings suggest that LCPUFAs play a role in immune development that is of clinical significance, particularly with regard to allergic sensitisation and allergic manifestations including wheeze and asthma.
α-Linolenic acid (ALA) is an n-3 fatty acid found in plant-derived foods such as linseeds and linseed oil. Mammals can convert this essential fatty acid into longer-chain fatty acids including EPA, ...docosapentaenoic acid (DPA) and DHA. Women demonstrate greater increases in the EPA status after ALA supplementation than men, and a growing body of animal model research identifies mechanisms by which sex hormones such as oestrogen and progesterone interact with the synthesis of EPA and DHA. Alternatively, EPA, DPA and DHA can be consumed directly, with oily fish being a rich dietary source of these nutrients. However, current National Diet and Nutrition Data reveals a median oily fish intake of 0 g daily across all age ranges and in both sexes. As longer-chain n-3 fatty acids have a crucial role in fetal and neonatal brain development, advice to consume dietary ALA could prove to be a pragmatic and acceptable alternative to advice to consume fish during pregnancy, if benefits upon tissue composition and functional outcomes can be demonstrated. Further research is required to understand the effects of increasing dietary ALA during pregnancy, and will need to simultaneously address conflicts with current dietary advice to only eat 'small amounts' of vegetable oils during pregnancy. Improving our understanding of sex-specific differences in fatty acid metabolism and interactions with pregnancy has the potential to inform both personalised nutrition advice and public health policy.
Findings from epidemiological and observational studies have indicated that diets high in omega-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid ...(EPA) may reduce the risk of cognitive decline and Alzheimer's disease (AD). To determine if increasing intake of DHA and EPA through supplementation is beneficial to cognition and mood in individuals with cognitive impairment no dementia (CIND) or Alzheimer's disease (AD) a four month, randomised, double-blind, placebo controlled study was conducted. Fifty-seven participants with CIND and nineteen with AD were randomised to receive either omega-3 PUFAs (600 mg EPA and 625 mg DHA per day) or placebo (olive oil) over a four month period. Elevating depleted levels of EPA and DHA through supplementation in individuals with CIND or AD was found to have negligible beneficial effect on their cognition or mood. These findings confirm an overall negligible benefit of omega-3 PUFA supplementation for those with cognitive impairment and dementia. More intervention studies need to be undertaken with longer study durations and larger sample sizes. It may prove fruitful to examine effects of different doses as well as effects in other dementia subtypes.
New perspectives on placental fatty acid transfer Lewis, Rohan M.; Childs, Caroline E.; Calder, Philip C.
Prostaglandins, leukotrienes and essential fatty acids,
November 2018, 2018-11-00, 20181101, Volume:
138
Journal Article
Peer reviewed
Open access
•Placental uptake of LC-PUFA are important to meet both foetal and placental demand.•Placental metabolism plays an important role in determining transfer of fatty acids to the foetus.•Metabolic ...targeting of specific fatty acids to different lipid pools may determine their availability as both nutrients and signalling molecules.•Fatty acids and their derivatives may mediate communication between the mother and placenta.
The human foetus depends on placental transfer for the fatty acids required for its growth and development. Long chain polyunsaturated fatty acids (LC-PUFAs) may specifically influence neurodevelopment. Therefore, it is important to understand the mechanisms of placental transfer of LC-PUFAs. The simple view of placental fatty acid transfer is that it occurs by diffusion down the maternal to foetal gradient, facilitated by membrane transporters. This view has been complicated by studies highlighting the role of placental metabolism in fatty acid transfer. Most fatty acids taken up by the placenta will be esterified and incorporated into lipid rather than diffusing directly across to the foetus. Furthermore, this esterification is likely to mean that placental intracellular “free” fatty acid concentrations are lower than in foetal plasma which would not be conducive to simple diffusion of fatty acids to the foetus. Placental structure poses additional questions, in particular how fatty acids cross the hydrophilic villous stroma separating the trophoblast from the endothelium and how they cross the endothelium itself. The understanding of placental fatty acid transfer needs to evolve to address these questions. The role of the placenta is not simply to mediate solute transfer; it is also a central endocrine organ of pregnancy. Placental-derived lipid mediators, such as prostaglandins, have well-established roles in parturition and, almost certainly, throughout gestation. Metabolic targeting of specific fatty acids to different lipid pools in the placenta may determine their availability as both nutrients and signalling molecules. Placental transfer will determine fatty acid availability within the foetus as well as influencing maternal levels. Fatty acids and their derivatives may also act as signals to the placenta indicating metabolic states in both mother and foetus. Placental uptake and metabolism of LC-PUFAs are important to meet both foetal and placental demands. This paper will review placental fatty acid transfer and metabolism and highlight issues which need to be addressed.
Epithelial cells (enterocytes) form part of the intestinal barrier, the largest human interface between the internal and external environments, and responsible for maintaining regulated intestinal ...absorption and immunological control. Under inflammatory conditions, the intestinal barrier and its component enterocytes become inflamed, leading to changes in barrier histology, permeability, and chemical mediator production. Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) can influence the inflammatory state of a range of cell types, including endothelial cells, monocytes, and macrophages. This review aims to assess the current literature detailing the effects of ω-3 PUFAs on epithelial cells. Marine-derived ω-3 PUFAs, eicosapentaenoic acid and docosahexaenoic acid, as well as plant-derived alpha-linolenic acid, are incorporated into intestinal epithelial cell membranes, prevent changes to epithelial permeability, inhibit the production of pro-inflammatory cytokines and eicosanoids and induce the production of anti-inflammatory eicosanoids and docosanoids. Altered inflammatory markers have been attributed to changes in activity and/or expression of proteins involved in inflammatory signalling including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator activated receptor (PPAR) α and γ, G-protein coupled receptor (GPR) 120 and cyclooxygenase (COX)-2. Effective doses for each ω-3 PUFA are difficult to determine due to inconsistencies in dose and time of exposure between different in vitro models and between in vivo and in vitro models. Further research is needed to determine the anti-inflammatory potential of less-studied ω-3 PUFAs, including docosapentaenoic acid and stearidonic acid.
Plasma lysophospholipids have emerged as signaling molecules with important effects on inflammation, insulin resistance, and fatty liver disease, each of which is linked closely to obesity. Dietary ...n-3 (ω-3) polyunsaturated fatty acids (PUFAs) may be able to improve these conditions.
The objective of this study was to assess the response of plasma lysophospholipids to obesity, n-3 PUFA consumption, and a high-fat meal challenge to better understand the role of lysophospholipid metabolism in the progression of obesity-related disorders.
We determined the concentrations of 8 lysophosphatidylcholines, 11 lysophosphatidylethanolamines, and 7 lysophosphatidylinositols in the plasma of 34 normal-weight and 38 obese subjects randomly assigned to consume corn oil (control) or n-3 PUFA-rich fish oil (3 g/d; n = 15-19/group) for 90 d. Blood samples were collected on the last day of the study under fasting conditions and 6 h after a high-fat meal (1135 kcal, 86 g fat) challenge. The profile of secreted lysophospholipids was studied in HepG2 cells under palmitate-induced steatosis.
Obese and normal-weight subjects had different profiles of plasma lysophospholipids. A multivariate combination of the 26 lysophospholipids could discriminate between normal-weight and obese subjects with an accuracy of 98%. The high-fat meal challenge altered the concentration of plasma lysophosphatidylcholines in an oil treatment-dependent manner in normal-weight but not obese subjects, suggesting that obesity impairs the sensitivity of lysophospholipid metabolism to n-3 PUFAs. Noncytotoxic steatosis in HepG2 cells affected the secretion pattern of lysophospholipids, partially resembling the changes observed in the plasma of obese subjects.
Obesity has a substantial impact on lysophospholipid metabolism, altering the plasma lysophospholipid profile and abolishing its sensitivity to dietary n-3 PUFAs. These effects could contribute to the onset or progression of alterations associated with obesity, such as inflammation, insulin resistance, and fatty liver disease. This trial was registered at www.controlled-trials.com as ISRCTN96712688.
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