The current study aimed to investigate the effects of ageing on oral immunity using β-defensin (DEFB) 1/2 as a marker and evaluate the effects of curcumin (CUR) on these processes. The study sample included thirty male C57BL/6J mice divided into three groups based on the treatment method used. The young control (YC) and old control (OC) groups received 0·5 % methylcellulose-400 (CUR vehicle) orally for 5 days, whereas the CUR group of older mice received a CUR solution suspended in 0·5 % methylcellulose-400 (dose: 3·0 mg/kg body). DEFB1/2 and immune indicator levels were measured in the saliva and salivary glands post-treatment. The saliva volume and protein content were significantly reduced in the OC group compared with the YC group. CUR administration restored these parameters, decreased DEFB1 expression in the salivary gland and increased DEFB1/2 secretion and DEFB2 expression. These findings were supported by epigenetic gene regulation and partial cytokine activation from changes in WD40 repeat protein 5, TNF alpha and IL-1beta. CUR can partially restore age-related changes in oral immune responses and promote oral health, thereby preventing frailty in the older population through a nutritional therapeutic pathway.

Ganoderma lucidum (a mushroom used in traditional Chinese medicine) compounds may attenuate ageing-related physiological changes and restore normal immunity. However, studies on the physiological effects of Ganoderma lucidum dry extract food supplements are few. Therefore, here, we aimed to investigate the effects of Ganoderma lucidum dry extract food supplement on the lymphocyte function of older women. This was a double-blind clinical trial (n 60) with a final 39 older volunteers, divided into two groups Ganoderma lucidum (n 23) and placebo (n 16). The Ganoderma lucidum group received 2000 mg/d of Ganoderma lucidum dry extract for 8 weeks. We used flow cytometry to determine the lymphocyte profile. CD4+ lymphocyte gene expression was evaluated by real-time polymerase chain reaction. We observed that in the Ganoderma lucidum group, concanavalin A stimulation increased lymphocyte proliferation. Further, we observed an increase in expression of Forkhead box P3, transforming growth factor-beta, IL-10, IL-6, retinoic acid receptor-related orphan receptor gamma, GATA-binding protein 3 and interferon gamma genes in the Ganoderma lucidum group. Furthermore, in the Ganoderma lucidum group, ionomycin and phorbol 12-myristate 13-acetate stimulation led to decrease in Th17+ cells and increase in Th2+ cells. Thus, in older women, Ganoderma lucidum regulates T lymphocyte function leading to a predominant anti-inflammatory action but does not induce T lymphocyte proliferation through CD28 signalling pathway.

Excessive hepatic glycogen accumulation commonly impairs hepatocytes function and further produces negative effects on growth and health status of carnivorous fish. A 9-week feeding trial was conducted to explore the potential regulation of resveratrol (RSV) on high-carbohydrate-induced glycogen deposition and immune response of largemouth bass. Results showed that high dietary carbohydrate (10 % inclusion of starch) led to hepatic glycogen accumulation and post-prandial hyperglycemia compared with the diet with 5 % starch, which was both alleviated with the inclusion of RSV. The use of RSV promoted the expression of sirtuin 1, which was down-regulated by high dietary carbohydrate. Meanwhile, RSV inclusion promoted the expression of genes involved in insulin pathway and glycolysis and inhibited the expression of gluconeogenesis-related genes. Additionally, high dietary carbohydrate significantly reduced lysozyme content but increased complement C4 content, which were both reversed with RSV supplementation. Meanwhile, RSV inclusion inhibited the expression of pro-inflammatory cytokines but promoted anti-inflammatory cytokines expression, compared with the high carbohydrate treatment. In conclusion, RSV inclusion was beneficial in alleviating high-dietary-carbohydrate-induced glycogen accumulation and immune response in largemouth bass.

The effects of monolaurin (ML) on the health of piglets infected with porcine epidemic diarrhoea virus (PEDV) have not been fully understood. This study aimed to investigate its role in blood biochemical profile, intestinal barrier function, antioxidant function and the expression of antiviral genes in piglets infected with PEDV. Thirty-two piglets were randomly divided into four groups: control group, ML group, PEDV group and ML + PEDV group. Piglets were orally administrated with ML at a dose of 100 mg/kg·BW for 7 d before PEDV infection. Results showed that PEDV infection significantly decreased D-xylose content and increased intestinal fatty acid-binding protein content, indicating that PEDV infection destroyed intestinal barrier and absorption function. While it could be repaired by ML administration. Moreover, ML administration significantly decreased plasma blood urea nitrogen and total protein content upon PEDV infection. These results suggested ML may increase protein utilisation efficiency. ML administration significantly decreased the number of large unstained cells and Hb and increased the number of leucocytes and eosinophils in the blood of PEDV-infected piglets, indicating ML could improve the immune defense function of the body. In the presence of PEDV infection, ML administration significantly increased superoxide dismutase and catalase activities in blood and colon, respectively, indicating ML could improve antioxidant capacity. Besides, ML administration reversed the expression of ISG15, IFIT3 and IL-29 throughout the small intestine and Mx1 in jejunum and ileum, indicating the body was in recovery from PEDV infection. This study suggests that ML could be used as a kind of feed additive to promote swine health upon PEDV infection.

Mate is a traditional drink obtained from the leaves of yerba mate and rich in a diversity of plant bioactive compounds including polyphenols, particularly chlorogenic acids. Studies, even though limited, suggest that consumption of mate is associated with health effects, including prevention of cardiometabolic disorders. Molecular mechanisms underlying the potential health properties are still largely unknown, especially in humans. The aim of this study was to investigate nutrigenomic effects of mate consumption and identify regulatory networks potentially mediating cardiometabolic health benefits. Healthy middle-aged men at risk for CVD consumed a standardised mate extract or placebo for 4 weeks. Global gene expression, including protein coding and non-coding RNA profiles, was determined using microarrays. Biological function analyses were performed using integrated bioinformatic tools. Comparison of global gene expression profiles showed significant change following mate consumption with 2635 significantly differentially expressed genes, among which six are miRNA and 244 are lncRNA. Functional analyses showed that these genes are involved in regulation of cell interactions and motility, inflammation or cell signalling. Transcription factors, such as MEF2A, MYB or HNF1A, could have their activity modulated by mate consumption either by direct interaction with polyphenol metabolites or by interactions of metabolites with cell signalling proteins, like p38 or ERK1/2, that could modulate transcription factor activity and regulate expression of genes observed. Correlation analysis suggests that expression profile is inversely associated with gene expression profiles of patients with cardiometabolic disorders. Therefore, mate consumption may exert cardiometabolic protective effects by modulating gene expression towards a protective profile.

Diet can affect health directly or by altering the gut microbiota; thus, there are strong interrelationships between the gut immune system, gut microbiota and diet. This study examined the effects of ingesting AIN-93M purified diet (PD) on gut immune function and gut microbiota in DO11·10 mice, in which T cell–dependent and T cell–independent (TI) IgA can be analysed separately. Ingestion of the PD for 2 weeks reduced both T cell–dependent and TI secretory IgA in the faeces compared with non-PD, whereas the diet did not affect T cell–dependent and TI serum IgA. Ingestion of the PD had no effect on systemic immune system splenocyte responses. Ingestion of the PD reduced intestinal tissue expression levels of B-cell activating factor and A proliferation–inducing ligand, cytokines involved in TI-IgA production and polymeric Ig receptor, which transports IgA into the intestinal lumen. Co-abundance group (CAG) analysis of the intestinal microbiota was conducted based on correlations between changes in the abundance of bacterial genera, and the correlations between CAG and IgA were determined. The Allobaculum-dominated CAG expanded following ingestion of the PD, accompanied by an inverse correlation with the decrease in faecal IgA, whereas the Lactobacillus-dominated CAG shrank relative to the Allobaculum-dominated CAG. These results suggest that TI-IgA suppresses the expansion of some intestinal bacteria and that ingestion of the PD induces dysbiosis via impaired IgA secretion into the intestinal lumen.

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 commentary highlighted the background, take-home messages, and impacts of our 2007 British Journal of Nutrition paper entitled “Amino acids and immune function”. In 2003–2004, there was an outbreak of severe acute respiratory syndrome (SARS) caused by SARS coronavirus-1 (CoV-1) in Asian countries. By the mid-2000’s, clinical and experimental evidence indicated important roles for amino acids (AA) in improving innate and adaptive immunities in humans and animals. Based on our long-standing interest in AA metabolism and nutritional immunology, we decided to critically analyze advances in this nutritional field. Furthermore, we proposed a unified mechanism responsible for beneficial effects of AA and their products (including nitric oxide, glutathione, antibodies, and cytokines) on immune responses. We hoped that such integrated knowledge would be helpful for designing AA-based nutritional methods (e.g., supplementation with glutathione, arginine and glutamine) to prevent and treat SARS-like infectious diseases in the future. Our paper laid a framework for subsequent studies to quantify AA metabolism in intestinal bacteria, determine the effects of functional AA on cell-mediated and humoral immunities, and establish a much-needed database of AA composition in foodstuffs. Unexpectedly, COVID-19 (caused by SARS-CoV-2) emerged in December 2019 and has become one of the deadliest pandemics in history. Notably, glutathione, arginine and glutamine have now been exploited to effectively relieve severe respiratory symptoms of COVID-19 in affected patients. Functional AA (e.g., arginine, cysteine, glutamate, glutamine, glycine, taurine and tryptophan) and glutathione, which are all abundant in animal-sourced foodstuffs, are crucial for optimum immunity and health in humans and animals.

Resistant starch (RS) has received increased attention due to its potential health benefits. This study was aimed to investigate the effects of dietary corn RS on immunological characteristics of broilers. A total of 320 broiler chicks were randomly allocated to five dietary treatments: normal corn–soyabean (NC) diet group, corn starch diet group, 4 %, 8 % and 12 % RS diet groups. This trial lasted for 42 d. The relative weights of spleen, thymus and bursa, the concentrations of nitric oxide (NO) and IL-4 in plasma at 21 d of age, as well as the activities of total nitric oxide synthase (TNOS) and inducible nitric oxide synthase (iNOS) in plasma at 21 and 42 d of age showed positive linear responses (P < 0·05) to the increasing dietary RS level. Meanwhile, compared with the birds from the NC group at 21 d of age, birds fed 4 % RS, 8 % RS and 12 % RS diets exhibited higher (P < 0·05) relative weight of bursa and concentrations of NO and interferon-γ in plasma. Birds fed 4 % RS and 8 % RS diets showed higher (P < 0·05) number of IgA-producing cells in the jejunum. While compared with birds from the NC group at 42 d of age, birds fed 12 % RS diet showed higher (P < 0·05) relative weight of spleen and activities of TNOS and iNOS in plasma. These findings suggested that dietary corn RS supplementation can improve immune function in broilers.

This randomised controlled trial examined the effect of a 4-week, high-dose (Lf-High, 600 mg/d) or low-dose (Lf-Low, 200 mg/d) oral lactoferrin (Lf) intervention v. placebo on immune cell responses to respiratory virus, immune cell subsets and systemic inflammation. In healthy older adults (n 103, ≥50 years old), ex vivo cytokine release of interferon (IFN)-α2, IFN-γ, IL-6 and TNF-α from rhinovirus A-16 (RV-16) or influenza A virus (H1N1) stimulated peripheral blood mononuclear cells, circulating immune cell subsets, and plasma IL-6, C-reactive protein (CRP) and TNF-α were assessed. Ninety-seven participants completed the 4-week intervention (Lf-High n 32, Lf-Low n 31, placebo n 34, withdrawals n 6). There was no difference in RV-16 or H1N1-induced IFN-γ release between groups. RV-16-induced IL-6 was lower in Lf-High v. placebo (P = 0·001), and RV-16-induced IFN-α2 was higher in Lf-High v. Lf-Low (P = 0·04). Lf-High increased total T cells (P = 0·03) and CD4+ T cells (P = 0·03) v. placebo. Lf-Low reduced neutrophil (P = 0·04), natural killer cell (P = 0·045), activated CD8+ T cell (P = 0·03) and γδ T cell (P = 0·03) frequency v. placebo. Plasma IL-6 (P = 0·004) and CRP (P = 0·03) were lower following Lf-High v. Lf-Low, but not placebo. Both high- and low-dose Lf altered ex vivo immune cell responses after 4 weeks. High-dose increased T-cell subsets, promoting adaptive immunity, and reduced systemic inflammation, while low-dose reduced proinflammatory and cytotoxic immune cells. High- and low-dose Lf supplements may have immunoceutical benefits in older adults.

A well-functioning immune system requires balanced immune responses. In vitro studies have shown that plant stanols contribute to restoring the T-helper (Th)1/Th2 ratio when it is imbalanced. However, effects of plant stanols on healthy immune responses are unknown. Therefore, we studied effects of recommended (2·5 g/d) or high (9·0 g/d) plant stanol intakes on the Th1/Th2 cytokine balance in immunologically healthy subjects. In two RCTs, peripheral blood mononuclear cells (PBMCs) were isolated, cultured, and stimulated with 5 µg/ml Phytohemagglutinin-M to study ex vivo cytokine production. In the first study, twenty participants consumed margarines (2·5 g/d plant stanols) or control for three weeks. In the second study, nineteen participants consumed margarines and yogurts (9·0 g/d plant stanols) or control for four weeks. T-cell cytokine concentrations were measured in culture medium and in study 2 a standardized Th1/Th2 index was calculated. Serum lipids and non-cholesterol sterols were also measured. Compliance was confirmed by significant increases in serum total cholesterol (TC)-standardized sitostanol and campestanol levels in both studies. Changes in ex vivo cytokine production and Th1/Th2 index did not differ between intervention and control groups. In the first study, no statistically significant changes were observed in lipid and lipoprotein concentrations. In the second study, LDL cholesterol significantly decreased compared to control (–0·77 (–1·11, –0·42) mmol/l; P < 0·001). Recommended (2·5 g/d) or high (9·0 g/d) intakes of plant stanols did not alter PBMC ex vivo cytokine production in immunologically healthy subjects. This suggests that plant stanols might only affect immune function when Th1/Th2 immune responses are imbalanced.

Inflammation and infections such as malaria affect concentrations of many micronutrient biomarkers and hence estimates of nutritional status. We aimed to assess the relationship between malaria infection and micronutrient biomarker concentrations in pre-school children (PSC), school-age children (SAC) and women of reproductive age (WRA) in Malawi and examine the potential role of malarial immunity on the relationship between malaria and micronutrient biomarkers. Data from the 2015/2016 Malawi micronutrient survey were used. The associations between current or recent malaria infection, detected by rapid diagnostic test and concentration of serum ferritin, soluble transferrin receptor (sTfR), zinc, serum folate, red blood cell folate and vitamin B12 were estimated using multivariable linear regression. Factors related to malarial immunity including age, altitude and presence of hemoglobinopathies were examined as effect modifiers. Serum ferritin, sTfR and zinc were adjusted for inflammation using the BRINDA method. Malaria infection was associated with 68 % (95 % CI 51, 86), 28 % (18, 40) and 34 % (13, 45) greater inflammation-adjusted ferritin in PSC, SAC and WRA, respectively (P < 0·001 for each). In PSC, the positive association was stronger in younger children, high altitude and children who were not carriers of the sickle cell trait. In PSC and SAC, sTfR was elevated (+ 25 % (16, 29) and + 15 % (9, 22) respectively, P < 0·001). Serum folate and erythrocyte folate were elevated in WRA with malaria (+ 18 % (3, 35) and + 11 % (1, 23), P = 0·01 and P = 0·003 respectively). Malaria affects the interpretation of micronutrient biomarker concentrations, and examining factors related to malarial immunity may be informative.

Zn is an important trace element involved in various biochemical processes in aquatic species. An 8-week rearing trial was thus conducted to investigate the effects of Zn on juvenile largemouth bass (Micropterus salmoides) by feeding seven diets, respectively, supplemented with no Zn (Con), 60 and 120 mg/kg inorganic Zn (Sul60 and Sul120), and 30, 60, 90 and 120 mg/kg organic Zn (Bio30, Bio60, Bio90 and Bio120). Sul120 and Bio120 groups showed significantly higher weight gain and specific growth rate than Con group, with Bio60 group obtaining the lowest viscerosomatic index and hepatosomatic index. 60 or 90 mg/kg organic Zn significantly facilitated whole body Zn retention. Up-regulation of hepatic superoxide dismutase, glutathione peroxidase and catalase activities and decline of malondialdehyde contents indicated augmented antioxidant capacities by organic Zn. Zn treatment also lowered plasma aminotransferase levels while promoting acid phosphatase activity and hepatic transcription levels of alp1, acp1 and lyz-c than deprivation of Zn. The alterations in whole body and liver crude lipid and plasma TAG contents illustrated the regulatory effect of Zn on lipid metabolism, which could be possibly attributed to the changes in hepatic expressions of acc1, pparγ, atgl and cpt1. These findings demonstrated the capabilities of Zn in potentiating growth and morphological performance, antioxidant capacity, immunity as well as regulating lipid metabolism in M. salmoides. Organic Zn could perform comparable effects at same or lower supplementation levels than inorganic Zn, suggesting its higher efficiency. 60 mg/kg supplementation of organic Zn could effectively cover the requirements of M. salmoides.

We aimed to investigate the intricate interplay between genetic predisposition and lifestyle factors on stroke. We conducted a comprehensive genome-wide association study to identify the genetic variants linked to stroke in the participants who experienced a stroke event (cases; n 672) and those with no stroke history (non-stroke; n 58 029) in a large hospital-based cohort. Using generalised multifactor dimensionality reduction, we identified genetic variants with interactive effects and constructed polygenic risk scores (PRS) by summing up the risk alleles from the genetic variants. Food intake was measured with a validated semi-quantitative FFQ. No significant differences in stroke incidence were seen in demographic variables between the two groups. Among the metabolic indicators, only serum TAG levels were higher in males with stroke than those without stroke. The daily nutrient intake, dietary inflammation index, glycaemic index, dietary patterns, alcohol consumption, exercise and smoking did not display associations with the OR for stroke. The stroke-linked genetic variants were related to the IL-18 pathway. After accounting for covariates, the PRS derived from the 5-, 6- and 7-SNP models were positively associated with stroke chance with 2·5-, 2·9- and 2·8-fold. Furthermore, interactions between genetic predisposition and dietary components, including energy, carbohydrates, n-3 fatty acids and branched-chain amino acids (BCAA), that affected OR for stroke were observed. A high intake of energy, carbohydrates and BCAA and a low intake of n-3 fatty acids were positively associated with the chances of stroke occurrence. In conclusion, understanding the interaction between genetic variants and lifestyle factors can assist in developing stroke prevention and management strategies.

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 importance of Se in human health has received much attention due to its antioxidant properties when it is consumed at an appropriate level. However, the existing evidence is limited to obtain an effective conclusion for colorectal cancer (CRC). Notably, an adequate intake of Se was reported for Koreans. Furthermore, cytokine secretion and immune function may be affected by dietary Se. Our study aimed to explore whether Se potentially reduces CRC risk and whether the IL10 rs1800871 polymorphism has an effect on this association. We designed a case–control study with 1420 cases and 2840 controls. A semi-quantitative FFQ was used to obtain information on Se intake. We determined IL10 rs1800871 through genetic analysis. Different models were developed to explore Se intake related to CRC risk by calculating OR and 95 % CI using unconditional logistic regression. A reduced risk of CRC was found as Se intake increased, with an OR (95 % CI) of 0·44 (0·35, 0·55) (Pfor trend < 0·001). However, this association seems to be allele-specific and only present among risk variant allele carriers (GA/GG) with a significant interaction between dietary Se and IL10 rs1800871 (Pfor interaction = 0·043). We emphasised that a reduction in CRC risk is associated with appropriate Se intake. However, the IL10 rs1800871 polymorphism has an impact on this reduction, with a greater effect on variant allele carriers. These findings suggest the importance of considering an individual’s genetic characteristics when developing nutritional strategies for CRC prevention.

Vitamin D (VD) plays a vital role in various physiological processes in addition to its classic functions on maintaining the balance of Ca and P metabolism. However, there still are gaps to understand in depth the issues on the precise requirement, metabolic processes and physiological functions of VD in fish. In this study, we investigated the effects of VD on the growth, intestinal health, host immunity and metabolism in turbot (Scophthalmus maximus L.), one important commercial carnivorous fish in aquaculture, through the supplementation of different doses of dietary VD3 (0, 200, 400, 800 and 1600 μg VD3/kg diet). According to our results, the optimal VD3 level in the feed for turbot growth was estimated to be around 400 μg/kg, whereas VD3 deficiency or overdose in diets induced the intestinal inflammation, lowered the diversity of gut microbiota and impaired the host resistance to bacterial infection in turbot. Moreover, the level of 1α,25(OH)2D3, the active metabolite of VD3, reached a peak value in the turbot serum in the 400 μg group, although the concentrations of Ca and phosphate in the turbot were stable in all groups. Finally, the deficiency of dietary VD3 disturbed the nutritional metabolism in turbot, especially the metabolism of lipids and glucose. In conclusion, this study evaluated the optimal dose of dietary VD3 for turbot and provided the evidence that VD has a significant impact on intestinal health, host immunity and nutritional metabolism in fish, which deepened our understanding on the physiological functions and metabolism of VD3 in fish.