European Journal of Nutrition最新文献

Purpose: Necrotizing enterocolitis (NEC) is the most severe gastrointestinal disease in preterm infants caused by an exaggerated intestinal epithelial immune activation. Several studies show that modulation of toll-like receptor 9 (TLR9) activity may have positive effects on preventing intestinal inflammatory mechanisms ultimately resulting in NEC development. In this study, the effect of various infant formulas (IF) and the probiotic strain Limosilactobacillus fermentum CECT5716 on TLR9 activation were analyzed in vitro.

Methods: First, TLR4 and TLR9 expression was analyzed on human primary intestinal epithelial cells (P-IECs) by qPCR and Western blot analysis. Then genetically designed HEK-Dual™ hTLR9 (NF/IL8) reporter cells (HEK-Dual) were treated with different IFs, L. fermentum CECT5716, and different functional components to measure TLR9 activation via luminescence. Finally, the IFs were investigated in P-IECs to analyze TLR downstream signaling by Western blot analysis.

Results: IFs containing intact protein and L. fermentum CECT5716 activated TLR9 in HEK-Dual cells, but the functional components lactoferrin, L-5-methyltetrahydrofolate, and hydrolyzed whey proteins failed to activate TLR9. In P-IECs, the IFs induced increased phosphorylation of MAPK8/9 of the TLR signaling pathway and significantly reduced IL6 levels. Consistently, IL6 levels were increased in P-IECs when TLR9-signaling was inhibited. Interestingly, L. fermentum CECT5716 enhanced TLR9-signaling and increased NF-kappa-B inhibitor alpha-phosphorylation.

Conclusion: We found out that the used control formula, prebiotic formula, prebiotic formula with hydrolyzed-protein, and L. fermentum CECT5716 reduce IL6 levels in human P-IECs through TLR9 activation. L. fermentum CECT5716 and the here tested IFs could be a promising approach for modulation of gut health in infants.

Purpose: To meet the global dietary protein demands, a trend towards plant-based protein (PBP) sources to replace animal-derived protein is currently ongoing. However, PBPs may not have the same anabolic capacity to stimulate muscle protein synthesis (MPS) as dairy proteins. For vulnerable populations with specific medical needs, it is especially important to validate the anabolic properties of PBPs. In this study, a blend of pea and soy protein isolate, with or without additional leucine, was compared to whey protein isolate on MPS in aged mice.

Methods: 25-Months aged C57BL/6J-mice received an oral gavage with 70 mg of whey protein isolate (W), PS protein isolate (PS; ratio 51:49), PS fortified with 19% leucine (PS + L), or 0.5mL water (F). Mice were subcutaneously injected with puromycin (0.04 µmol/g body weight, t = 30 min) and sacrificed 60 min thereafter. Left m. tibialis anterior (TA) was used to analyse MPS by the SUnSET method and mTOR signal transduction proteins. Amino acid concentrations were determined in plasma and right TA. Dried blood spots (DBS) were analysed for postprandial dynamics of amino acids at 10-20-45-60-min.

Results: MPS was significantly increased by W and PS + L (p < 0.003), however not by PS. Pathway protein 4EBP1 showed significant increases with W, PS and PS + L to F (p < 0.0002). W and PS + L increased plasma and muscle free leucine equally, which was confirmed by DBS.

Conclusion: A PS blend fortified with leucine stimulates MPS comparable to whey protein in this acute murine ageing model. Leucine appears to be the main driver for the anabolic responses observed.

Purpose: Pharmacological inhibition of ferroptosis, a specific form of regulated cell death, has emerged as a promising therapeutic strategy for alleviating symptoms and enhancing endoscopic outcomes in patients suffering from ulcerative colitis. Rhoifolin, a prominent bioactive constituent abundant in the widely consumed fruit Citrus grandis (grapefruit), has garnered attention for its ability to diminish the levels of reactive oxygen species (ROS), which are key inducers of ferroptosis across diverse cellular contexts. In this study, we aimed to investigate whether rhoifolin exerts its beneficial effects on colitis by modulating the process of epithelial ferroptosis.

Methods: Colitis model was successfully established in C57BL/6 mice through the administration of 2.5% dextran sulfate sodium (DSS) solution for a duration of 9 days, which was freely accessible for drinking. RNA sequencing was conducted to delve into the mechanisms underlying the rhoifolin-mediated effects on colitis. To evaluate the impact of rhoifolin on ferroptosis in epithelial cells, several key indicators were measured, including mitochondrial morphology, colonic glutathione (GSH) levels, lipid peroxidation product contents, and ROS levels.

Results: The results indicated that rhoifolin exhibited profound anti-colitis properties and effectively curbs ferroptosis in epithelial cells of mice subjected to DSS treatment. The RNA sequencing analysis further revealed that rhoifolin stimulated a remarkable upregulation of colonic cell migration-inducing protein (CEMIP) expression by approximately 2.4-fold in colitis-affected mice. Notably, depletion of CEMIP significantly blocked the rhoifolin-induced increase in the cystine transporter solute carrier family 7 member 11 (SLC7A11, from 1.9-fold to approximately 1.1-fold), as well as the elevation of cystine uptake (from 1.72-fold to 1.2-fold) and glutathione (GSH) biosynthesis (from 2.1-fold to 1.2-fold), and the suppression of epithelial ferroptosis (from 0.51-fold to 0.94-fold) in mice with colitis. Molecular docking investigations have pinpointed crucial amino acid residues within CEMIP, specifically His267, His289, and Phe265, as the primary interaction sites (docking score: -7.8 kcal/mol), facilitating the engagement of rhoifolin via hydrogen bonding interactions.

Conclusion: Rhoifolin significantly mitigated DSS-induced colitis primarily through inhibiting epithelial ferroptosis. The activation of CEMIP by citrus-derived rhoifolin led to a notable upregulation of SLC7A11 expression, thereby enhanced cystine uptake and facilitated GSH biosynthesis, ultimately suppressed the occurrence of ferroptosis in epithelial cells.

Purpose: Vitamin K is an activator of vitamin K dependent proteins, one of which is the potent inhibitor of vascular calcification, matrix Gla protein (MGP). The purpose of this study is to investigate the association between an inverse proxy of functional vitamin K status, plasma dephospho-uncarboxylated MGP (dp-ucMGP), and cardiovascular disease risk factors (CVDRFs).

Methods: In a cross-sectional population-based health examination study of 4,092 individuals aged 24-77 years, the vitamin K status was assessed using plasma dp-ucMGP. All participants were linked to Danish National Prescription Register to obtain information on the use of vitamin K antagonists. The associations between log2 transformed dp-ucMGP values and CVDRFs were determined using regression models adjusted for sex, age, lifestyle factors, kidney function and waist circumference.

Results: Higher dp-ucMGP levels were associated with increased risk of central obesity (Odds Ratio (OR) 4.76, 95% Confidence Intervals (CI) 3.57-6.34), diabetes (OR 1.96, 95% CI 1.11-3.45), hyperlipidaemia (OR 1.43, 95% CI 1.01-2.03), and impaired kidney function (OR 9.83, 95% CI 5.49-17.59) per doubling in dp-ucMGP. Dp-ucMGP was not independently associated with hypertension or arterial stiffness.

Conclusion: Higher dp-ucMGP levels were associated with central obesity, diabetes, hyperlipidaemia, and impaired kidney function. Prospective studies and intervention studies examining the effects of improving vitamin K status are needed to clarify the potential role of vitamin K in relation to these CVDRFs.

Purpose: Carbohydrate intake has been linked to colorectal cancer (CRC) risk, with variations depending on the quantity and quality of carbohydrates consumed. This study aimed to investigate the association between carbohydrate quantity and quality, using the low-carbohydrate diet score (LCD) and carbohydrate quality index (CQI), and the risk of CRC in the Chinese population.

Methods: We conducted a case-control study in Guangzhou, China, with 2,799 CRC cases and an equal number of sex- and age-matched controls. Dietary data were collected using a validated food frequency questionnaire to derive the LCD and CQI, assessing the quantity and quality of carbohydrate intake separately. Odds ratios (OR) and 95% confidence interval (CI) for CRC risk were estimated using unconditional logistic regression models, and restricted cubic splines were used to explore potential non-linear relationships.

Results: The results demonstrated that higher adherence to the overall LCD score, plant-based LCD score, and CQI was associated with a lower risk of CRC. The adjusted ORs (95%CIs) for the highest quintile of intake in comparison with the lowest quintile were 0.76 (0.63, 0.91) for the overall LCD score, 0.61 (0.50, 0.74) for the plant-based LCD score, and 0.70 (0.58,0.84) for the CQI, respectively. However, the animal-based LCD did not show a significant association with CRC risk, with the adjusted OR (95%CI) for the highest quintile compared to the lowest being 0.98 (0.81, 1.18). Restricted cubic splines analysis showed non-linear associations of the overall LCD score, animal-based LCD score, and plant-based LCD score with CRC risk. In contrast, a linear relationship was observed between CQI and CRC risk (P_nonlinear = 0.594).

Conclusions: Our findings indicate that the overall LCD score, the plant-based LCD score, and the CQI were inversely associated with the risk of CRC.

Purpose: Diet rich in antioxidant may protect against chronic respiratory disease (CRD), but few studies have evaluated the association between composite dietary antioxidant index (CDAI) and CRD. The study aimed to examine the association of CDAI with the risk of CRD and all-cause mortality in CRD patients from the US.

Methods: Data were obtained from the National Health and Nutrition Examination Survey, 2003-2018. Logistic and Cox regression analyses were used to estimate association of CDAI with CRD and all-cause mortality. Dose-response relationship was examined by restricted cubic spline analyses.

Results: Total 44,094 participants were eligible for CRD (aged 1-85 years; mean age: 45.71 years old), and 7,685 CRD patients for all-cause mortality (median follow-up: 7.58 years; 1,136 deaths before 12/31/2019). The risk for CRD, asthma, and chronic obstructive pulmonary disease was significantly decreased by 13-32% with the increase intake of CDAI, even after adjusting for confounders (all P < 0.001). The relationship between CDAI and three respiratory endpoints was U-shaped (all P for nonlinearity < 0.001). There was an obvious declining trend in the magnitude of mortality risk with the increase of intake of CDAI, especially in patients with asthma. Fully adjusted hazard ratio was 0.72 (95% confidence interval: 0.54-0.95), 0.55 (0.42-0.72), and 0.48 (0.34-0.66) for the second, third, and fourth quartile of CDAI in patients with asthma relative to the first quartile, respectively. The association with CRD risk was significantly modified by smoking status (P-interaction: 0.006).

Conclusion: Our findings indicate that high CDAI is a significant protective factor against CRD and all-cause mortality in the US population.

Purpose: We designed and evaluated food-based dietary recommendations for 12-24-mo-old New Zealand children with linear and goal programming models taking into account intakes of all nutrients concurrently.

Methods: Dietary data used to define model parameters (food list, food quantities consumed, and food consumption patterns from 3-d weighed food records) were collected from 12-24-mo-old New Zealand toddlers (n = 188). Linear and goal programming models were developed to design and evaluate three sets of recommendations: (1) using all foods consumed by toddlers; (2) excluding commercial infant/toddler foods; and (3) excluding both commercial infant/toddler foods and all iron-fortified foods.

Results: Food-based dietary recommendations for toddlers were developed which aligned with observed food consumption patterns: Non-Sweet Cereals: 3 serves/d, Vegetables: 2 serves/d, Fruit: 2 serves/d, Dairy: 2 serves/d, and Meat/Fish/Poultry/Eggs/Legumes/Nuts: 2 serves/d. However, they only ensured adequate intakes of all nutrients modeled if ≈ 500 g/d of iron-fortified toddler milk was also recommended. Food-based dietary recommendations that excluded commercial infant/toddler foods or excluded both commercial infant/toddler foods and all iron-fortified foods would not ensure adequate intakes of iron and folate, for all children. The lowest intakes, in simulated intake distributions for these nutrients, were ≤ 29% and ≤ 38% of their nutrient reference values, respectively.

Conclusions: Food-based dietary recommendations which successfully promote the consumption of 3 serves/d of Non-Sweet Cereals, 2 serves/d of Vegetables, 2 serves/d of Fruit, 2 serves/d of Dairy (including ≈ 500 g/d of iron-fortified toddler milk), and 2 serves/d of Meat/Fish/Poultry/Eggs/Legumes/Nuts should ensure all New Zealand toddlers meet their requirements for the 15 nutrients modeled.

Background: Multiple diet patterns play a crucial role in the development of colorectal cancer and its precursor, colorectal adenoma, but mediating effect of plasma metabolite profiles is unclear.

Methods: A total of 95,275 participants from UK Biobank with plasma metabolomics and dietary information were analyzed. Metabolite profile scores for 14 dietary patterns were estimated through elastic net regression. Cox regression analysis assessed the associations of dietary patterns and their metabolite profile scores with colorectal tumor risk. Mediating effects of identified metabolite profile scores were estimated in the associations.

Results: Fourteen metabolite profile scores, including a range of 28 to 205 signatures, were weak to moderate correlation with dietary patterns (all p < 0.001). Multivariable Cox regression analyses revealed that five dietary patterns were significantly correlated with a decreased risk of colorectal tumor after FDR correction and adjustment for covariates. HRs (95% CIs) per 1 SD for these diet patterns were as follows: WCRF (0.93, 0.90-0.96), CRC score (0.94, 0.92-0.97), AHEI-2010 (0.95, 0.92-0.97), DASH (0.94, 0.91-0.97), and hPDI (0.95, 0.93-0.98). Similarly, metabolite profile scores for these five dietary patterns were inversely associated with colorectal tumor risk, with HRs (95% CIs) per 1 SD as follows: WCRF (0.59, 0.49-0.70), CRC score (0.67, 0.58-0.77), AHEI-2010 (0.73, 0.65-0.80), DASH (0.75, 0.66-0.84), and hPDI (0.56, 0.47-0.67). The mediation proportions of five metabolite profile scores between dietary patterns and colorectal tumor risk ranged from 6.37 to 27.23% (all p < 0.001).

Conclusions: Five dietary patterns and their metabolite profile scores, were inversely correlated with colorectal tumor risk. These findings highlight the potential of metabolite profiles as mediators in the association between dietary patterns and the risk of colorectal tumor, further contributing to the prevention of colorectal cancer or adenoma and providing new insights for future research.

Purpose: Threonine (Thr) can be involved in the synthesis of immunoglobulins, which play the role of immune regulation, Thr also has to improve intestinal morphology, adjust the sticky protein synthesis, maintain the intestinal barrier function, etc. The experiment aimed to investigate the effects of diets supplemented with different levels of Thr on growth performance and intestinal health of rabbits under lipopolysaccharide (LPS) stress conditions.

Methods: A total of 180 healthy 35-day-old weaned New Zealand White rabbits were randomly assigned in a 2 × 3 factorial design to receive an intraperitoneal injection of 100 µg/kg BW LPS or saline and three diets with different levels of digestible threonine (0.43%, 0.54%, and 0.64%).

Results: The LPS challenge resulted in a reduction in body weight in rabbits at day 22, as well as a decrease in the serum d-lactic acid (D-LA) content and the number of goblet cells (GCs) in the jejunum. Additionally, the duodenum JAM2 and JAM3 were down-regulated. The expression of OCLN, ZO-1, and IL-2 in the jejunum, and CLDN, nuclear factor-κB (NF-κB) and ZO-1 mRNA in the ileum were also down-regulated. Furthermore, the duodenum TLR4 and IL-1β mRNA expression, while the jejunum exhibited an elevation in CLDN, TNF-α, and ileum TNF-α mRNA expression (P < 0.05). In the context of LPS challenge condition, dietary Thr addition was found to down-regulate the duodenum ZO-1 and jejunum CLDN mRNA expression of rabbits (P < 0.05). This was accompanied by an increase in ileum sIgA content and GCs number (P < 0.05). Additionally, dietary Thr addition resulted in a downregulation of duodenum TLR4, MyD88, NF-κB, TNF-α and IL-1β, jejunum MyD88, and IL-1β mRNA expression, as well as an up-regulation of ileum IL-10 mRNA expression in rabbits (P < 0.05).

Conclusion: In conclusion, the LPS challenge can result in intestinal inflammation and damage the integrity of the intestinal barrier in rabbits. Nevertheless, dietary Thr supplementation can alleviate the intestinal inflammatory response in rabbits challenged with LPS.

Background: The global climate crisis requires a paradigm shift in dietary concepts, respecting the needs of children. A global reference diet has been suggested by the EAT-Lancet Commission. On this basis, the detailed "Planetary Health Diet Index" (PHDI) has been proposed. The objective of this assessment is (1) to apply the PHDI to the Food-Based Dietary Guidelines, the so-called Optimized Mixed Diet (OMD) for children and adolescents in Germany in its original composition and (2) to check how the planetary value of the OMD could be improved by modifying food selection within meals while keeping the high nutrient densities of the guideline diet.

Methods: The PHDI specifies 16 food groups and their proportion of total daily energy intake. The PHDI of the original OMD was calculated by assigning the foods of the 7-day menu to the PHDI food groups in order to score them. In this way, it became apparent which food groups had the potential to improve the sustainability. The diet was then updated by either reducing or increasing individual foods from these food groups in the meals and deriving the resulting PHDI. The nutrient densities of the original and updated daily OMD were calculated.

Results: The original diet obtained a PHDI score of 68.24 points, representing 45.5% of the theoretical maximum of 150 points. The following food groups achieved 9.9 to 10 out of 10 points: fruits, total vegetables, fish & seafood, vegetable oils, chicken (and substitutes). Conversely, food groups receiving a zero score included tubers & potatoes, dairy, red meat, animal fat, and added sugars. The updated diet resulted in increased consumption of 'nuts & peanuts', 'legumes', 'green vegetables', 'whole grains', and decreased consumption of 'tubers & potatoes' and 'red meat'. Overall, the PHDI increased from 68.24 to 81.51 points with the updated OMD, reflecting a 13.27% increase compared to the original diet. The nutrient densities were not significantly affected, but even slightly increased for most nutrients.

Conclusions: The PHDI was applied to demonstrate how the sustainability of the guideline diet for children and adolescents in Germany could be improved through changes in individual food groups that can be easily implemented in practice while maintaining high nutrient densities and acceptability for children.

Trial registration: NA.