This study was conducted to investigate the effects of blended oils with a balanced n-6/n-3 PUFA ratio of 6:1 and unsaturated fatty acid/SFA (UFA/SFA) ratio of 2·5:1 on growth performance and intestinal health in lipopolysaccharide (LPS)-challenged piglets. One hundred and twenty piglets were selected and randomly assigned to two treatments (2 % soybean oil or 2 % blended oils). On day 28, the experiment was conducted as a 2 × 2 factorial arrangement of treatments, including dietary treatment (2 % soybean oil v. 2 % blended oil) and LPS challenge (saline v. LPS). The results showed that the blended oils supplementation increased average daily gain and average daily feed intake during 1–14 d (P < 0·05), and reduced feed to gain ratio in the whole experimental period (P < 0·05). In addition, the blended oils supplementation improved intestinal morphology, increased maltase and sucrase activities and alleviated inflammation response in the intestine. Moreover, the blended oils supplementation increased proliferating cell nuclear antigen mRNA expression in jejunum and Ki67 mRNA expression in ileum (P < 0·05) in both saline-treated piglets and LPS-challenged piglets. The blended oils reduced C-myc and caspase-3 mRNA expressions and increased Axin2 and Cyclin d1 mRNA expressions after LPS challenge (P < 0·05). In conclusion, the blended oils can improve growth performance and promote intestinal health in piglets.

Metabolic dysregulation increases the risk of cognitive and motor deficits, exacerbated by diets high in refined carbohydrates and fats. Polyphenol-rich berries, such as red raspberries (RRB; Rubus idaeus), may offer protective benefits. This randomised, single-blinded, controlled crossover study evaluated the acute metabolic and cognitive effects of RRB intake in older adults (55–70 years) with overweight/obesity. Thirty-six adults (61 (sd 5) years, BMI: 30·0 (sd 2·8) kg/m2; 19 females: 17 males) consumed a high-carbohydrate, moderate-fat meal (56 % carbohydrate, 33 % fat) containing 0 g (control) or 25 g of freeze-dried RRB powder. Plasma was collected at baseline and postprandially over 7·5 h to assess glucose, insulin, triacylglyceride (TAG) and IL-6. In vitro, fasting and postprandial serum samples were applied to lipopolysaccharide (LPS)-stimulated microglial cells to assess neuroinflammatory responses (nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) expression). Cognitive and vascular function were assessed at baseline and postprandially. The RRB meal significantly reduced peak glucose (by 8 %), insulin concentrations at 0·5 h and overall insulin response compared with control (P < 0·05). Serum from RRB consumers attenuated LPS-induced NO, iNOS and COX-2 expression in microglial cells (P < 0·001). Cognitive performance improved following the RRB meal, with fewer attempts in the CANTAB (Cambridge Neuropsychological Test Automated Battery) Paired Associates Learning task (P < 0·05) and fewer errors with better strategy use in the Spatial Working Memory task (P < 0·05). No significant differences were observed in vascular function. These findings suggest that acute RRB supplementation attenuated postprandial metabolic stress, reduced markers of neuroinflammation and improved cognitive performance, supporting RRB’s potential role in a dietary strategy for ageing populations.

This study explored the effects of different preparations of Akkermansia muciniphila (AKK) on the gut microbiota and jejunal transcriptome of lipopolysaccharide (LPS) challenged yellow-feathered broilers. A total of 100 one-day-old broilers were divided into five groups, including control group (Control), LPS injection (LPS), gavage of AKK broth culture plus LPS injection (AKK), gavage of viable AKK suspension plus LPS injection (Active) and gavage of heat-inactivated AKK suspension plus LPS injection (Inactive). Growth performance results showed that LPS significantly reduced the body weight of broilers. Alpha diversity showed no significant group differences. At the phylum level, Firmicutes was significantly lower in groups with AKK gavage. At the genus level, Bacteroides was relatively more abundant, whereas Streptococcus was numerically less abundant in AKK-treated groups. The Active group had the highest abundance of Akkermansia. Transcriptome analysis revealed the Inactive group had significantly lower Occludin. Combined KEGG and GO analyses revealed that the LPS challenge suppressed innate immunity by downregulating the Retinoic acid-inducible gene (RIG)-I-like receptor signaling pathway. In response, different interventions distinctly modulated the transcriptome. The AKK group counteracted this suppression by upregulating innate immune and antiviral defense responses. The Active group primarily influenced metabolism, downregulating pathways for drug and glutathione metabolism and xenobiotic responses while upregulating retinol metabolism. In addition, the Inactive group demonstrated an upregulation of ribosome biogenesis, and energy metabolism, suggesting a restoration of core cellular functions. In summary, all gavaged AKK preparations maintained broiler gut microbiome stability, while AKK broth culture demonstrated superior efficacy in alleviating LPS-induced jejunal stress.

Coconut oil, extracted from coconut kernels, is a rich source of medium-chain fatty acids, including lauric acid, capric acid and caprylic acid. This experiment aimed to investigate the protective effect of coconut oil against intestinal injury induced by lipopolysaccharide (LPS) challenge in piglets. A total of twenty-four piglets were used in a 2 × 2 factorial experiment with dietary treatment (3 % soybean oil v. 3 % coconut oil) and LPS challenge (saline v. LPS). After 28 d of the experiment, piglets were injected intraperitoneally with LPS (100 μg/kg body weight (BW)) or saline. Piglets were slaughtered and sampled for testing. Pigs fed coconut oil had higher average daily gain and BW during the entire study. Supplementation with coconut oil improved intestinal morphology and barrier function, indicated by increased jejunal villus height, as well as enhanced protein expression of ZO-1 and Occludin. Furthermore, coconut oil supplementation improved plasma antioxidant capacity, indicated by enhanced GSH peroxidase activity and decreased malondialdehyde concentration. Moreover, coconut oil ameliorated the LPS-induced release of pro-inflammatory cytokines, as indicated by decreased IL-1β expression in the jejunum. Coconut oil also alleviated the up-regulation of the expression of necroptosis protein receptor-interacting protein kinase 3 and mixed lineage kinase-like protein in the jejunum of piglets stimulated by LPS. In conclusion, dietary supplementation of coconut oil can improve the growth performance of piglets and alleviate LPS-induced intestinal injury and inflammation by inhibiting necroptosis signalling pathway.

Marathon runners, subjected to intense training regimens and prolonged, exhaustive exercises, often experience a compromised immune response. Probiotic supplementation has emerged as a potential remedy to mitigate the impact of prolonged exercise on athletes. Consequently, this study sought to assess the influence of probiotic supplementation on monocyte functionality both before and after the official marathon race. Twenty-seven runners were randomly and double-blindly assigned to two groups: placebo (n 13) and probiotic (PRO) (n 14). Over 30 d, both groups received supplements – placebo sachets containing maltodextrin (5 g/d) and PRO sachets containing 1 × 1010 colony-forming unit Lactobacillus acidophilus and 1 × 1010 colony-forming unit Bifidobacterium bifidum subsp. lactis. Blood samples were collected, and immunological assays, including phagocytosis, hydrogen peroxide production, cytokine levels and monocyte immunophenotyping, were conducted at four different intervals: baseline (start of supplementation/30 d pre-marathon), 24 h-before (1 d pre-marathon), 1 h-after (1 h post-marathon) and 5 d-after (5 d post-marathon). Monocyte populations remained consistent throughout the study. A notable increase in phagocytosis was observed in the PRO group after 30 d of supplementation. Upon lipopolysaccharide stimulation, both PRO and placebo groups exhibited decreased IL-8 production. However, after the marathon race, IL-15 stimulation demonstrated increased levels of 5 d-after, while IL-1-β, IL-8, IL-10, IL-15 and TNF-α varied across different intervals, specifically within the PRO group. Probiotic supplementation notably enhanced the phagocytic capacity of monocytes. However, these effects were not sustained post-marathon.

This study is aimed to evaluate the effect and underling mechanism of dietary supplementation with pyrroloquinoline quinone (PQQ) disodium on improving inflammatory liver injury in piglets challenged with lipopolysaccharide (LPS). A total of seventy-two crossbred barrows were allotted into four groups as follows: the CTRL group (basal diet + saline injection); the PQQ group (3 mg/kg PQQ diet + saline injection); the CTRL + LPS group (basal diet + LPS injection) and the PQQ + LPS group (3 mg/kg PQQ diet + LPS injection). On days 7, 11 and 14, piglets were challenged with LPS or saline. Blood was sampled at 4 h after the last LPS injection (day 14), and then the piglets were slaughtered and liver tissue was harvested. The results showed that the hepatic morphology was improved in the PQQ + LPS group compared with the CTRL + LPS group. PQQ supplementation decreased the level of serum inflammatory factors, aspartate aminotransferase and alanine transaminase, and increased the HDL-cholesterol concentration in piglets challenged with LPS; piglets in the PQQ + LPS group had lower liver mRNA level of inflammatory factors and protein level of α-smooth muscle actin than in the CTRL + LPS group. Besides, mRNA expression of STAT3/TGF-β1 pathway and protein level of p-STAT3(Tyr 705) were decreased, and mRNA level of PPARα and protein expression of p-AMPK in liver were increased in the PQQ + LPS group compared with the CTRL + LPS group (P < 0·05). In conclusion, dietary supplementation with PQQ alleviated inflammatory liver injury might partly via inhibition of the STAT3/TGF-β1 pathway in piglets challenged with LPS.

The precision nutrition paradigm is based on the premise that substantial variation exists between human subjects in terms of diet-related disease risk and response to dietary interventions. In terms of better defining, ‘the right diet for the right person at the right time’ may be more appropriate than ‘one-diet-fits-all’. This review will explore how systems biology and nutrigenomics approaches have advanced the precision nutrition paradigm. We will draw upon a number of elegant mechanistic studies that have enhanced our understanding with respect to the complex biology and inter-organ crosstalk, relating to inflammation and metabolism, that underpin cardio-metabolic health. Also, this review will explore the extent to which more targeted, precision nutrition approaches may attenuate adverse risk factors associated with cardio-metabolic disease. We will focus on the key characteristics or ‘metabotypes’ of high- v. low-risk individuals and response v. non-response to interventions, to generate greater insights with respect to risk stratification and therapeutic interventions to enhance disease prevention. The goal is to utilise systems biology to enhance understanding by underpinning more targeted nutritional approaches, which may improve efficacy of personalised nutrition interventions.

The relationship between non-communicable diseases and eating behaviour has long been attributed to a surplus of food and energy. However, the increase in the prevalence of non-communicable disease and their underlying low-grade inflammatory milieu among people of low socio-economic status has highlighted the existence of a confounding factor. In this work, we aim to study the effect of lysine deficiency on some inflammatory markers in the absence or presence of an inflammatory insult (lipopolysaccharide (LPS)). For this purpose, thirty-two 5-week-old male Sprague Dawley rats were randomly distributed into four groups: (1) control diet, (2) control diet+LPS, (3) lysine-deficient diet and (4) lysine-deficient diet + LPS. Groups were only allowed their experimental diets for 4 weeks, during which LPS (50 µg/kg) or saline injections were administered intraperitoneally three times per week. The study showed that lysine deficiency blunted growth and body compartments development, decreased albumin production and elevated liver C-reactive protein (CRP) expression, independently of IL-6 and IL-1β, the main precursors of CRP. Also, the insufficient levels of lysine in the diet increased hyperactivity and triggered an anxiety-like behaviour, exacerbated with LPS. This work presents evidence that various physiological changes are associated with the absence of a sufficient amount of lysine in the diet and can potentially increase the risk factor for diseases. Thus, the increment in non-communicable disease among the low socio-economic status populations, who heavily rely on cereals as a main source of protein, can be, at least partially, blamed on low lysine availability in diets.

Homeostasis of gut microbiota is a critical contributor to growth and health in weaned piglets. Fish oil is widely reported to benefit health of mammals including preventing intestinal dysfunction, yet its protective effect during suckling-to-weaning transition in piglets remains undetermined. Low (30 g/d) and high (60 g/d) doses of n-3-rich fish oil were supplemented in sows from late gestation to lactation. Serum indicators and gut microbiota were determined to evaluate the effects of maternal fish oil on growth performance, immunity and diarrhea of piglets. DHA and EPA in the colostrum as well as serum of suckling and 1-week post-wean piglets were significantly and linearly increased by maternal supplementation of fish oil (P < 0.05). IGF1 and T3 in nursing and weaned piglets were significantly elevated by maternal fish oil (P < 0.05), and the increase of IGF1 was concerning the dosage of fish oil. Colostrum IgG, plasma IgG, IgM in suckling piglets, IgG, IgM and IgA in weaned piglets were significantly increase as maternal replenishment of fish oil increased (P < 0.05). Additionally, cortisol was significantly reduced in weaned pigs (P < 0.05), regardless of dosage. 16S rRNA sequencing revealed that α-diversity of fecal microbiota in nursery piglets, and fecal Lactobacillus genus, positively correlated with post-weaning IgA, was significantly increased by high dosage. Collectively, maternal fish oil during late pregnancy and lactation significantly promoted growth, enhanced immunity, and reduced post-weaning diarrhea in piglets, therefore facilitated suckling-to-weaning transition in piglets, which may be partially due to the altered gut microbial community.

Major depressive disorder (MDD) is regarded as an inflammatory disorder. Gut microbiota dysbiosis, observed in both MDD and obesity, leads to endotoxemia and inflammatory status, eventually exacerbating depressive symptoms. Manipulation of gut microbiota by prebiotics might help alleviate depression. The present study aimed to investigate the effects of inulin supplementation on psychological outcomes and biomarkers of gut permeability, endotoxemia, inflammation, and brain-derived neurotrophic factor (BDNF) in women with obesity and depression on a calorie-restricted diet. In a double-blind randomised clinical trial, forty-five women with obesity and MDD were allocated to receive 10 g/d of either inulin or maltodextrin for 8 weeks; all the patients followed a healthy calorie restricted diet as well. Anthropometric measures, dietary intakes, depression, and serum levels of zonulin, lipopolysaccharide (LPS), inflammatory biomarkers (TNF-α, IL-10, monocyte chemoattractant protein-1, toll-like receptor-4 and high-sensitivity C-reactive protein), and BDNF were assessed at baseline and end of the study. Weight and Hamilton Depression Rating Scale (HDRS) scores decreased in both groups; between-group differences were non-significant by the end of study (P = 0·333 for body weight and P = 0·500 for HDRS). No between-group differences were observed for the other psychological outcomes and serum biomarkers (P > 0·05). In this short-term study, prebiotic supplementation had no significant beneficial effects on depressive symptoms, gut permeability, or inflammatory biomarkers in women with obesity and depression.

Hesperidin and naringin are citrus flavonoids with known anti-oxidative and anti-inflammatory properties. Evidence from previous studies indicates that both these compounds and the metabolites that are formed during intestinal metabolism are able to exert beneficial effects on intestinal barrier function and inflammation. However, so far, studies investigating the relative contributions of the various compounds are lacking. Therefore, we assessed the effect of citrus flavonoids and their intestinal metabolites on immune-mediated barrier disruption in an in vitro co-culture model. Caco-2 cell monolayers were placed in co-culture with phorbol 12-myristate 13-acetate-stimulated THP-1-Blue™ NF-κB cells for 30 h. At baseline, the citrus flavonoids and their metabolites were added to the apical compartment (50 or 100 µM per compound). After 24 h, THP-1 cells were incubated with lipopolysaccharide (LPS) in the basolateral compartment for 6 h. Incubation with citrus flavonoids and their metabolites did not induce changes in transepithelial electrical resistance, fluorescein isothiocyanate–dextran 4 kDa permeation or gene expression of barrier-related genes for any of the compounds tested. After LPS stimulation, NF-κB activity was significantly inhibited by all compounds (100 µM) except for one metabolite (all P ≤ 0·03). LPS-induced production of the cytokines IL-8, TNF-α and IL-6 was inhibited by most compounds (all P < 0·05). However, levels of IL-1β were increased, which may contribute to the lack of an improved barrier effect. Overall, these results suggest that citrus flavonoids may decrease intestinal inflammation via reduction of NF-κB activity and that the parent compounds and their metabolites formed during intestinal metabolism are able to exert comparable effects.

The current study aimed to investigate the protective effects of dietary thiamine supplementation on the regulation of colonic integrity and mucosal inflammation in goats fed a high-concentrate (HC) diet. Twenty-four Boer goats (live weight of 35·62 (sem 2·4) kg) were allocated to three groups (CON: concentrate/forage = 30:70; HC; concentrate/forage = 70:30 and HCT: concentrate/forage = 70:30 with 200 mg thiamine/kg DMI) for 12 weeks. Results showed that compared with the HC treatment, the HCT group had a significantly higher ruminal pH value from 0 to 12 h after the feeding. The haematoxylin–eosin staining showed that desquamation and severe cellular damage were observed in the colon epithelium of the HC group, whereas the HCT group exhibited more structural integrity of the epithelial cell morphology. Compared with the HC treatment, the HCT group showed a markedly increase in pyruvate dehydrogenase and α-ketoglutarate dehydrogenase enzymes activity. The mRNA expressions in the colonic epithelium of SLC19A2, SLC19A3, SLC25A19, Bcl-2, occludin, claudin-1, claudin-4 and ZO-1 in the HCT group were significantly increased in comparison with the HC diet treatment. Compared with the HC treatment, the HCT diet significantly increased the protein expression of claudin-1 and significantly decreased the protein expression of NF-κB-related proteins p65. The results show that dietary thiamine supplementation could improve the colon epithelial barrier function and alleviate mucosal inflammation injury in goats after lipopolysaccharide and low pH challenge.

Legumes are a staple of diets all around the world. In some least developed countries, they are the primary source of protein; however, their beneficial properties go beyond their nutritional value. Recent research has shown that legumes have bioactive compounds like peptides, polyphenols and saponins, which exhibit antioxidant, antihypertensive, anti-inflammatory and other biological activities. Thus, these compounds could be an alternative treatment for inflammatory diseases, in particular, chronic inflammation such as arthritis, obesity and cancer. Nowadays, there is a growing interest in alternative therapies derived from natural products; accordingly, the present review has compiled the bioactive compounds found in legumes that have demonstrated an anti-inflammatory effect in non-clinical studies.

Consumption of edible insects has been widely suggested as an environmentally sustainable substitute for meat to reduce greenhouse gas emissions. However, the novel research field for edible insects relies on the content of bioactive ingredients and on the ability to induce a functional effect in humans. The goal of this manuscript is to review the available body of evidence on the properties of edible insects in modulating oxidative and inflammatory stress, platelet aggregation, lipid and glucose metabolism and weight control. A search for literature investigating the functional role of edible insects was carried out in the PubMed database using specific keywords. A total of 55 studies, meeting inclusion criteria after screening, were divided on the basis of the experimental approach: in vitro studies, cellular models/ex vivo studies or in vivo studies. In the majority of the studies, insects demonstrated the ability to reduce oxidative stress, modulate antioxidant status, restore the impaired activity of antioxidant enzymes and reduce markers of oxidative damage. Edible insects displayed anti-inflammatory activity reducing cytokines and modulating specific transcription factors. Results from animal studies suggest that edible insects can modulate lipid and glucose metabolism. The limited number of studies focused on the assessment of anti-coagulation activity of edible insects makes it difficult to draw conclusions. More evidence from dietary intervention studies in humans is needed to support the promising evidence from in vitro and animal models about the functional role of edible insect consumption.

Brucellosis is one of the most serious and widespread zoonotic diseases, which seriously threatens human health and the national economy. This study was based on the T/B dominant epitopes of Brucella outer membrane protein 22 (Omp22), outer membrane protein 19 (Omp19) and outer membrane protein 28 (Omp28), with bioinformatics methods to design a safe and effective multi-epitope vaccine. The amino acid sequences of the proteins were found in the National Center for Biotechnology Information (NCBI) database, and the signal peptides were predicted by the SignaIP-5.0 server. The surface accessibility and hydrophilic regions of proteins were analysed with the ProtScale software and the tertiary structure model of the proteins predicted by I-TASSER software and labelled with the UCSF Chimera software. The software COBEpro, SVMTriP and BepiPred were used to predict B cell epitopes of the proteins. SYFPEITHI, RANKpep and IEDB were employed to predict T cell epitopes of the proteins. The T/B dominant epitopes of three proteins were combined with HEYGAALEREAG and GGGS linkers, and carriers sequences linked to the N- and C-terminus of the vaccine construct with the help of EAAAK linkers. Finally, the tertiary structure and physical and chemical properties of the multi-epitope vaccine construct were analysed. The allergenicity, antigenicity and solubility of the multi-epitope vaccine construct were 7.37–11.30, 0.788 and 0.866, respectively. The Ramachandran diagram of the mock vaccine construct showed 96.0% residues within the favoured and allowed range. Collectively, our results showed that this multi-epitope vaccine construct has a high-quality structure and suitable characteristics, which may provide a theoretical basis for future laboratory experiments.

The present study was conducted to test the hypothesis that dietary supplementation with a nano chitosan–zinc complex (CP–Zn, 100 mg/kg Zn) could alleviate weaning stress in piglets challenged with enterotoxigenic Escherichia coli K88 by improving growth performance and intestinal antioxidant capacity. The in vivo effects of CP–Zn on growth performance variables (including gastrointestinal digestion and absorption functions and the levels of key proteins related to muscle growth) and the antioxidant capacity of the small intestine (SI) were evaluated in seventy-two weaned piglets. The porcine jejunal epithelial cell line IPEC-J2 was used to further investigate the antioxidant mechanism of CP–Zn in vitro. The results showed that CP–Zn supplementation increased the jejunal villus height and decreased the diarrhoea rate in weaned piglets. CP–Zn supplementation also improved growth performance (average daily gain and average daily feed intake), increased the activity of carbohydrate digestion-related enzymes (amylase, maltase, sucrase and lactase) and the mRNA expression levels of nutrient transporters (Na+-dependent glucose transporter 1, glucose transporter type 2, peptide transporter 1 and excitatory amino acid carrier 1) in the jejunum and up-regulated the expression levels of mammalian target of rapamycin (mTOR) pathway-related proteins (insulin receptor substrate 1, phospho-mTOR and phospho-p70S6K) in muscle. In addition, CP–Zn supplementation increased glutathione content, enhanced total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-px) activity, and reduced malondialdehyde (MDA) content in the jejunum. Furthermore, CP–Zn decreased the content of MDA and reactive oxygen species, enhanced the activity of T-SOD and GSH-px and up-regulated the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway-related proteins (Nrf2, NAD(P)H:quinone oxidoreductase 1 and haeme oxygenase 1) in lipopolysaccharide-stimulated IPEC-J2 cells. Collectively, these findings indicate that CP–Zn supplementation can improve growth performance and the antioxidant capacity of the SI in piglets, thus alleviating weaning stress.

Hyperprolific sows rear more piglets than they have teats, and to accommodate this, milk replacers are often offered as a supplement. Milk replacers are based on bovine milk, yet components of vegetable origin are often added. This may reduce growth, but could also accelerate maturational changes. Therefore, we investigated the effect of feeding piglets a milk replacer with gradually increasing levels of wheat flour on growth, gut enzyme activity and immune function compared with a diet based entirely on bovine milk. The hypothesis tested was that adding a starch component (wheat flour) induces maturation of the mucosa as measured by higher digestive activity and improved integrity and immunity of the small intestines (SI). To test this hypothesis, piglets were removed from the sow at day 3 and fed either a pure milk replacer diet (MILK) or from day 11 a milk replacer diet with increasing levels of wheat (WHEAT). The WHEAT piglets had an increased enzyme activity of maltase and sucrase in the proximal part of the SI compared with the MILK group. There were no differences in gut morphology, histopathology and gene expression between the groups. In conclusion, the pigs given a milk replacer with added wheat displayed immunological and gut mucosal enzyme maturational changes, indicatory of adaptation towards a vegetable-based diet. This was not associated with any clinical complications, and future studies are needed to show whether this could improve responses in the subsequent weaning process.

Inflammation is a normal part of the immune response and should be self-limiting. Excessive or unresolved inflammation is linked to tissue damage, pathology and ill health. Prostaglandins and leukotrienes produced from the n-6 fatty acid arachidonic acid are involved in inflammation. Fatty acids may also influence inflammatory processes through mechanisms not necessarily involving lipid mediators. The n-3 fatty acids EPA and DHA possess a range of anti-inflammatory actions. Increased content of EPA and DHA in the membranes of cells involved in inflammation has effects on the physical nature of the membranes and on the formation of signalling platforms called lipid rafts. EPA and DHA interfere with arachidonic acid metabolism which yields prostaglandins and leukotrienes involved in inflammation. EPA gives rise to weak (e.g. less inflammatory) analogues and both EPA and DHA are substrates for the synthesis of specialised pro-resolving mediators. Through their effects on early signalling events in membranes and on the profile of lipid mediators produced, EPA and DHA alter both intracellular and intercellular signals. Within cells, this leads to altered patterns of gene expression and of protein production. The net result is decreased production of inflammatory cytokines, chemokines, adhesion molecules, proteases and enzymes. The anti-inflammatory and inflammation-resolving effects of EPA and DHA are relevant to both prevention and treatment of human diseases that have an inflammatory component. This has been widely studied in rheumatoid arthritis where there is good evidence that high doses of EPA + DHA reduce pain and other symptoms.