Frontiers in Nutrition最新文献

Purpose: Ursodeoxycholic acid (UDCA), a naturally occurring bile acid with established hepatoprotective properties, has garnered attention for its potential role in metabolic health. This study provides scientific validation for these traditional uses by demonstrating UDCA's protective mechanisms against non-alcoholic fatty liver disease (NAFLD) through gut microbiota modulation and metabolic regulation. This study elucidates the therapeutic mechanisms of UDCA against high-fat diet-induced NAFLD through integrated microbiota-metabolomics analysis.

Methods: Using a 12-week murine NAFLD model, oral UDCA (15 mg/kg/day and 30 mg/kg/day) was administered to evaluate its hepatoprotective effects. Hepatic steatosis and injury were assessed via serum ALT/AST levels, lipid profiles, and histopathology. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) quantified bile acid metabolites, while 16S rRNA sequencing analyzed gut microbiota composition. Serum metabolomics and network pharmacology were employed to identify metabolic pathways and mechanistic targets, respectively. Molecular analyses (qPCR/Western blot) assessed PPARγ/Nrf2/NF-κB signaling.

Results: UDCA treatment significantly ameliorated high-fat diet-induced NAFLD, as demonstrated by improved serum ALT/AST levels, attenuated hepatic steatosis, and reduced histopathological damage. UPLC-MS/MS analysis revealed a marked reorganization of bile acid metabolism, characterized by elevated non-12α-hydroxylated bile acids (UDCA, TUDCA) and enhanced alternative synthesis via CYP27A1 upregulation. 16S rRNA sequencing identified UDCA-driven restructuring of the gut microbiota, with specific enrichment of short-chain fatty acid-producing Muribaculum spp. and suppression of pro-inflammatory Prevotella (CAG-485). Serum metabolomics further confirmed these benefits, showing increased eicosapentaenoic acid (anti-inflammatory) and decreased long-chain acylcarnitines (lipid peroxidation markers). At the molecular level, UDCA activated PPARγ/Nrf2 antioxidative signaling while inhibiting NF-κB-mediated inflammation, and network pharmacology analysis identified 225 potential targets (including TNF-α, IL6, and NF-κB) within lipid/atherosclerosis pathways, collectively underscoring UDCA's multimodal protective mechanisms against NAFLD.

Conclusion: These findings validate UDCA's multifaceted hepatoprotection via microbiota-bile acid crosstalk and metabolic-inflammatory modulation. The study provides a mechanistic basis for UDCA's traditional use in hepatobiliary disorders by integrating microbial, metabolic, and molecular evidence.

Background: This study aims to evaluate the efficacy of Guiling Prescription (GP)-a medicinal food homologous formula-in hyperuricemic rats, its effects on uric acid excretion and renal function, and to clarify the metabolic mechanisms involved in GP's alleviation of hyperuricemia.

Methods: Sprague-Dawley (SD) rats of hyperuricemia was established using potassium oxonate (200 mg/kg, PO) and adenine (100 mg/kg) to assess the therapeutic effects of Guiling Prescription (GP). We measured body weight, serum levels of uric acid and creatinine, as well as xanthine oxidase (XOD) and adenosine deaminase (ADA) activity, alongside histopathological parameters. Serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined using ELISA kits. The expression of renal uric acid transporters was evaluated through Western blotting. Network pharmacology was utilized to predict the key drug-disease targets, and a non-targeted metabolomic assay was applied to identify the key metabolites and metabolic pathways, and validated these targets through molecular docking and western blot analyses.

Results: GP showed an improvement effect on hyperuricemia model rats, with decreased levels of serum uric acid (UA), serum urea nitrogen, and creatinine, and serum ALT, AST. Furthermore, H&E staining results showed to improve renal injury in the hyperuricemic rat, and serum interleukin-6 and tumor necrosis factor-αwere improve the body's inflammatory response after administration of GP. In addition, GP could regulate multiple serum metabolic pathways such as arachidonic acid metabolism, pyrimidine metabolism, purine metabolism, citric acid cycle. On one side, GP decreased the synthesis of uric acid by inhibiting hepatic xanthine oxidase activities and adenosine deaminase activity. On the other side, GP increased the excretion of uric acid with the upregulation of UA excretion genes ABCG2, OAT1, and OAT3 and downregulation of UA resorption genes URAT1 and GLUT9.

Conclusion: GP orchestrates uric acid metabolism through multi-target and multi-pathway regulation, highlighting its potential not only as a novel therapeutic strategy but also as a promising dietary supplement for the management of hyperuricemia.

Background: Plant-based diets may lower breast cancer risk, but their impact on breast cancer-related mortality is unclear. We explored associations of plant-based dietary patterns (Healthful Plant-Based Diet Index [HPDI/PDI]) and micronutrient intake with breast cancer incidence and all-cause mortality in patients.

Methods: Using data of UK Biobank (UKB; 67,045 cancer-free participants; 3,397 breast cancer patients) and Chinese Longitudinal Healthy Longevity Survey (CLHLS), we analyzed dietary scores and micronutrient intake via multivariate Cox regression, restricted cubic splines, and predictive models (concordance index, Random Forest, and time-dependent ROC).

Results: Among 67,045 breast cancer-free participants, the highest HPDI tertile was associated with 11% lower breast cancer risk (HR = 0.89, 95%CI: 0.82-0.98) vs. lowest tertile (4% reduction per SD increase, HR = 0.96, 95%CI: 0.93-1.00). Among 3,397 breast cancer patients, the highest HPDI tertile showed 28% lower mortality (HR = 0.72, 95%CI: 0.55-0.95) vs. lowest (11% reduction per SD, HR = 0.89, 95%CI: 0.79-1.00). Individuals with high PDI scores exhibited a 39% lower risk of cancer compared to those with low scores in CLHLS (HR = 0.61, 95%CI: 0.41-0.92). Higher intakes of vitamins B2 and C, calcium, and magnesium were inversely associated with risk and mortality, while each SD increase in sodium raised mortality risk by 15% (HR = 1.15, 95%CI: 1.01-1.32). Predictive models showed optimal 5-year performance overall; micronutrients alone best predicted breast cancer risk across timepoints, while HPDI peaked for 5-year mortality prediction (AUC = 0.625). The combined model achieved superior 10-year prognosis.

Conclusions: High adherence to a healthful plant-based diet, together with sufficient intake of key micronutrients and reduced sodium consumption, may contribute to breast cancer prevention and improved survival outcomes.

Background: While sleep quality and chronotype are critical to wellbeing, the role of dietary diversity remains scarcely investigated, particularly among young and middle-aged adults. This study aimed to examine the associations of dietary diversity with sleep quality and chronotype, and to explore whether depression mediates these relationships.

Methods: Data were derived from the 2024-2025 China Nutrition and Sleep Survey (CNSS), including 4,128 adults aged 20-59 years. Dietary diversity indices, including total dietary diversity scores (DDS), plant-based DDS, animal-based DDS, anti-inflammatory diet diversity index (AIDDI) and protein-enriched diet diversity index (PEDDI), were calculated from food frequency questionnaires. Sleep quality, chronotype, and depression were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Morningness-Eveningness Questionnaire-5 (MEQ-5), and the Patient Health Questionnaire-9 (PHQ-9), respectively. Linear and logistic regression analyses were performed, with propensity score matching (PSM) applied to reduce confounding. Mediation and interaction analyses were further conducted.

Results: Higher dietary diversity indices were significantly associated with lower PSQI scores and higher MEQ-5 scores, both before and after PSM. Depression might be partially involved in the observed associations with sleep quality and chronotype. The associations between dietary diversity and sleep quality were stronger among females, older adults, non-drinkers, and those with regular exercise or depressive symptoms, whereas associations with chronotype were generally consistent across subgroups.

Conclusions: Greater dietary diversity is associated with better sleep quality and earlier chronotype, with depressive symptoms potentially playing a role in explaining these associations.

Background: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates cellular defense mechanisms and has been proposed as a therapeutic target for Alzheimer's disease (AD). Preclinical studies suggest that long-term oral administration of glucoraphanin (GLR), a natural Nrf2 activator, mitigates age-related cognitive decline in animal models.

Objective: This study evaluated the long-term efficacy of GLR supplementation on cognitive function in older adults at an elevated risk for AD, including those with mild cognitive impairment (MCI).

Methods: In a 42-month randomized, double-blind, placebo-controlled trial, 26 participants aged 63-90 years with memory impairment were randomly assigned to receive either 30 mg/day of GLR (n = 13) or placebo (n = 12). The primary outcome was the change in Memory Performance Index (MPI) scores from the MCI Screen. Secondary outcomes included conversion/reversion rates between normal cognition and MCI.

Results: Ten participants in the GLR group and nine participants in the placebo group completed the trial. Analysis using a Linear Mixed Model (LMM) across the entire study period revealed a significant group by time-point interaction for MPI scores, with the GLR group showing a significantly greater improvement in MPI scores compared to the placebo (p = 0.012). No significant group difference was observed in the initial 6 months, but a marginal difference in favor of GLR appeared in the later phase (30 and 42 months), including the 42-month endpoint (p = 0.079). Conversion/reversion rates were not significantly different. The GLR group demonstrated superior performance on immediate recall and delayed free recall tests (p < 0.001 and p = 0.012, respectively). MCI participants showed a greater MPI improvement with GLR (p = 0.029). No severe adverse events related to the intervention were reported.

Conclusion: Long-term GLR supplementation may help preserve cognitive function in individuals at elevated risk for AD, particularly those with MCI. Larger trials are warranted to confirm efficacy and clarify underlying mechanisms.

Background: Breast cancer heterogeneity is influenced by tumor grade, molecular subtype, and modifiable lifestyle factors such as diet and nutritional status. Tumor aggressiveness and oxidative stress may be influenced by dietary habits and serum nutritional profiles, according to new research.

Aim: The purpose of this study was to assess the relationship between oxidative stress markers, dietary patterns, serum nutritional profiles, and breast cancer tumor features, such as tumor grade and molecular subtype.

Methodology: Using validated questionnaires, the tumor grade, molecular subtype, serum nutrients (vitamins, trace elements, lipids, oxidative stress indicators), and food intake of 293 female patients with breast cancer were evaluated in this retrospective analysis. Dietary patterns were found using principal component analysis, and statistical analyses included correlation matrices and logistic regression.

Results: The molecular subtypes of the tumors were Luminal A (38.2%), Luminal B (24.9%), HER2-enriched (21.3%), and triple-negative (15.7%). The tumor grades were Grade I (29.8%), II (45.5%), and III (24.7%). With tumor grade, oxidative stress (MDA) rose and antioxidant nutrients decreased (p < 0.01). Plant-based, Western, Mixed, and Mediterranean-like eating patterns were found. While the Mediterranean-like diet was beneficial (OR = 0.60, p = 0.041), excessive adherence to the Western diet was linked to increased risks of aggressive tumors (OR = 2.30, p = 0.003). Antioxidant nutrients and adherence to the Mediterranean-like diet were shown to be favorably correlated; MDA was positively correlated with the Western pattern.

Conclusion: Antioxidant-rich Mediterranean-like dietary pattern showed inverse association with aggressive tumor features, suggesting potential protective biological relationship while Western dietary pattern was positively associated with oxidative stress and lower circulating antioxidant nutrients. Personalized nutrition methods to improve breast cancer prognosis may be informed by the integration of dietary and biochemical assessment.

Background: Shenqi compound (SQC) is an effective prescription in Chinese medicine to enhance glucose homeostasis and protect pancreatic cells from high glucose-induced damage. However, the protection mechanism remains unclear.

Objective: To investigate the effect of SQC on INS-1 cell secretion and evaluate the associated mechanisms.

Methods: INS-1 cells were cultured in serum augmented with or without NOD1 inhibitor ML130 (2μM) for 1 h, then exposed into a high glucose (50 mM) condition to simulate type 2 diabetes mellitus (T2DM) for 24 h and treated with different concentrations (0, 5, 10, 15, 20%) of SQC in serum for another 24 h. Then, the cell counting kit-8 (CCK-8) method, glucose-stimulated insulin secretion (GSIS) assay, transmission electron microscopy (TEM), real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-qPCR), and Western blot were performed for further investigation.

Results: Under high glucose conditions, 15% SQC was the optimal therapeutic concentration, significantly improved INS-1 cell viability (p = 0.032) and enhanced insulin secretion (p < 0.0001). Ultrastructural analysis showed that after high glucose stimulation in GSIS, especially at 20 min, 15% SQC significantly increased both the total density (p = 0.143) and the mature ratio (p = 0.003) of insulin secretory vesicles. Furthermore, 15% SQC facilitated the dynamic transport of vesicles toward the cell membrane, evidenced by an increased vesicle density within 300 nm of the membrane at 10 min, followed by a subsequent decrease at 20 min-a trend consistent with that observed in the control group. Moreover, at the molecular level, 15% SQC intervention markedly up-regulated NOD1 and RIP2 protein expression (p = 0.029 and p < 0.0001) and transcription (p = 0.886 and p = 0.393) levels, while ML130 reversed the activation of the NOD1/RIP2 pathway.

Conclusions: SQC promotes the maturation and transport of insulin secretory vesicles, thereby enhancing the secretory function of INS-1 cells in response to high glucose-induced damage. This protective effect may be associated with the activation of the NOD1/RIP2 signaling pathway.

Background: Magnesium is an important mineral that plays a role in many biochemical reactions in the body. Since it plays a role in many mechanisms of the body, it is thought that it may also have effects on stress and headaches.

Methods: The study was conducted with the participation of a total of 150 volunteer academic and administrative staff aged between 19 and 65. Participants were evaluated through general information, anthropometric measurements, Headache Impact Test-6 (HIT-6) and Perceived Stress Level Scale-10 (PSS-10), 3-day food consumption record and frequency of consumption of magnesium-rich foods questionnaire.

Results: The mean age of the participants was 31 ± 6.283 years for men and 28.55 ± 5.294 years for women. The Headache Impact Test-6 score was higher in the group with inadequate magnesium intake (p < 0.05). Although the Perceived Stress Level Scale-10 score was also higher in the group with inadequate magnesium intake, the result was not significant (p > 0.05). A negative correlation was found between dietary magnesium and HIT-6 and PSS-10 scores (r = -0.183, r = -0.197, respectively; p < 0.05). A positive correlation was also found between the scales (r = 0.456; p < 0.01).

Conclusion: These findings suggest that lower dietary magnesium intake is associated with higher headache impact and perceived stress in academic and administrative staff.

Postmenopause is commonly associated with vasomotor symptoms, musculoskeletal discomfort, weight gain, gastrointestinal (GI) disturbances, and increased cardiometabolic and autoimmune risk. A 52-year-old woman presented with hot flashes, weight gain, joint stiffness and pain, and abdominal bloating. Genomic profiling revealed variants affecting methylation, detoxification, and metabolic regulation. Functional testing identified global sex hormone decline, impaired Phase II estrogen metabolism, vitamin D insufficiency, an atherogenic lipid profile, increased intestinal permeability, and elevated toxin burden. A phased, precision nutrition plan was implemented, combining dietary modification, targeted nutraceuticals, gut-directed therapy, detoxification support, sleep optimization, and stress management, alongside bioidentical hormone replacement therapy (BHRT). After 6 months, the patient experienced resolution of vasomotor symptoms and GI bloating, marked reduction in musculoskeletal pain and Medical Symptoms Questionnaire (MSQ) scores, improved sleep quality, and favorable lipid changes. This case demonstrates the potential of genomically informed precision nutrition, integrated with functional testing, to guide personalized interventions that enhance metabolic health, symptom resolution, and overall quality of life (QoL) in postmenopausal women.