Journal of Nutritional Biochemistry最新文献

We previously demonstrated that prenatal choline supplementation (CS) mitigates metabolic abnormalities in mouse offspring exposed to maternal obesity. In this preliminary study we examined whether prenatal and postnatal CS can protect against the development of metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring exposed to an obesogenic environment. C57BL/6J mice were exposed to a maternal high-fat (HF) diet in utero and a postnatal Western Diet (WD) to induce MASLD. Choline was supplemented before and during gestation and lactation, after weaning, or throughout these periods. We found that maternal HF worsened histological scoring of MASLD when offspring were exposed to the WD during the postnatal period (HF-WD) (p < 0.05). Lifelong CS was the most effective on mitigating glucose intolerance, hepatomegaly, visceral adiposity, and histological scoring of steatohepatitis compared to HF-WD without CS or with CS in the prenatal or postnatal period only (all p < 0.05). HF-WD increased leptin levels (p < 0.05) which was mitigated by lifelong CS in offspring of both sexes. HF-WD led to global DNA hypermethylation (p < 0.05) in male offspring only, which was prevented by CS at any time point. Deuterium label (d9) tracing of choline metabolism demonstrated that CS at any time point increased choline oxidation as reflected by the elevated d9-betaine/d9-choline enrichment ratio yet reduced choline-derived methyl group use for the remethylation as reflected by the lower d3-methionine/d9-betaine ratio (p < 0.05). In conclusion, lifelong CS provided an effective approach to alleviate the severity of MASLD programmed by prenatal and postnatal obesogenic feeding in mice.

Aging-associated cognitive impairment (CI) is a core feature of neurodegenerative diseases, profoundly affecting the daily life of patients. Microglial dysfunction significantly contributes to the pathogenesis of CI. The gut-brain axis serves as a pivotal regulator of microglial functions, making it a promising target for halting the development and progression of CI. Deciphering the mechanisms of the gut-microglia-brain (GMB) axis may help devise potential therapeutic strategies to mitigate CI. This review first describes the recent progress in the development and functions of microglia, including the latest advancements in this field. Subsequently, the dynamic and complex communications between microglia and the gut microecosystem, including intestinal cells, gut microbiota, gut microbiota-derived metabolites, gut-derived exosomes, and intestinal bacteriophages, were discussed. Finally, current therapeutic strategies targeting the GMB axis to mitigate CI, such as lifestyle interventions, fecal microbiota transplantation (FMT), phages, exosomes, and pharmacological therapies, were summarized. The understanding of GMB axis-mediated cognitive function may pave the way for the identification of novel therapeutic strategies to mitigate aging-associated CI.

Depression, or major depressive disorder (MDD), is a prevalent psychological disorder, but its underlying mechanisms remain understood, hindering effective prevention and treatment. This study investigated the protective effects of quercetin on CUMS-induced depressive-like behaviors and explored the underlying mechanisms using in vivo and in vitro experiments. Metabonomic analysis revealed that chronic unpredictable mild stress (CUMS) significantly elevated serum levels of argininosuccinic acid (ASA), which were strongly correlated with depression-like behaviors in rats, suggesting a potential role of ASA in depression pathogenesis. Intracerebral injection of ASA induced depression-like behaviors and upregulated inflammatory markers (IKK-α, P65, NLRP3) and pyroptosis-related proteins (Caspase-1, Gasdermin D) in the rats hippocampus. Quercetin treatment ameliorated CUMS-induced depressive behaviors, reduced serum ASA levels, and inhibited hippocampal inflammation and pyroptosis. In subsequent vitro experiments with primary astrocytes isolated from the hippocampus of neonatal rats aged 1-3 days, ROS, NLRP3, and caspase-1 inhibitors were used to demonstrate that quercetin, through its antioxidant and anti-inflammatory effects, could attenuate ASA-induced activation of the NF-κB/NLRP3 inflammatory pathway and subsequent pyroptosis, thereby protecting astrocytes. Collectively, this study suggested that ASA could induce NLRP3/caspase-1 activation via ROS, triggering astrocyte pyroptosis and contributing to depression. Notably, quercetin can effectively alleviate stress-induced depression-like behaviors by inhibiting ASA-induced astrocyte pyroptosis and subsequent astrocyte loss in the hippocampus. This study provides valuable insights into the potential of quercetin as a therapeutic agent targeting cellular mechanisms in depression, offering new perspectives for treating this disorder.

Short-chain fatty acids (SCFAs) production by fermented foods is a promising health strategy regarding inflammation and oxidative stress regulation. However, there is uncertainty whether probiotic yogurt is truly superior to conventional yogurt. This systematic review and meta-analysis aimed to evaluate current evidence on the effect of probiotic yogurt on SCFAs, oxidative stress, and inflammatory biomarkers. A systematic literature search was performed up to December 2025 on PubMed, Scopus, Embase, Web of Science and LILACS. Only randomized controlled trials and crossover studies were included. A random-effects meta-analysis of standardized mean difference (SMD) was performed. A total of 15326 articles were selected. After full-text review, 33 trials were considered. Pooled analysis showed a statistically significant increase in fecal acetate levels (SMD 0.29; 95% CI: 0.02; 0.57). No significant differences were found for propionate, butyrate, and total SCFAs. Subgroup analysis revealed significant differences between study design in acetate and butyrate. Similarly, no significant difference was found for C-reactive protein (SMD -0.61; 95% CI: -2.25; 1.03) and oxidative stress biomarkers. In contrast, interleukin-10 showed a significant increase (SMD 0.48; 95% CI: 0.15; 0.80). Current evidence comparing probiotic yogurt with conventional yogurt is very limited. Preliminary findings suggest increments of clinically uncertain relevance in fecal acetate levels and interleukin-10. However, due to the very low certainty of the evidence, superiority over conventional yogurt is uncertain. Further trials are needed to standardize follow-up time, doses and to address possible effect modification by study design. Registration: PROSPERO registration number: CRD42024534718.

This study investigated the effects of maternal nutrition on hepatic long non-coding RNA (lncRNA) expression in Nellore cattle offspring. To this end, a total of 126 pregnant cows were assigned to three dietary treatments: NP (mineral supplementation only), PP (late protein-energy supplementation), and FP (protein-energy supplementation throughout pregnancy). At 676 ± 28 days of age, liver samples were collected from the offspring to perform RNA-Sequencing. Novel lncRNAs were identified with FEELnc and CPC2, and differentially expressed lncRNAs (DELs) with DESeq2. Partial Correlation and Information Theory, and Regulatory Impact Factor were used to identify key regulatory roles, while over-representation analysis was performed to detect enriched processes. Among the 3,257 lncRNAs identified, 17 were DELs (FDR < 0.1). The PPxNP comparison exhibited the highest transcriptional changes (10 DELs), including IncRNA TU7296, identified as a potential regulator of energy metabolism and immune function, as well as molecular functions associated with oxidative metabolism. The FPxNP comparison revealed distinct regulation of genes related to fatty acid transport and oxidative protein folding. The FPxPP comparison showed minimal differences, highlighting the similarity between these groups. This study provides insights into the role of maternal nutrition in modulating long-term epigenetic programming via lncRNA-mediated mechanisms in beef cattle offspring.

Maternal antibiotic use can increase obesity risk in offspring. Co-administering prebiotics mitigates the risk in rats. How prebiotics and antibiotics interact to affect obesity risk is unknown but could involve altered milk microbiota that influences offspring gut colonization. Sprague-Dawley rat dams were exposed to antibiotics (low-dose penicillin) and/or prebiotics (oligofructose) during gestation and lactation. Gut and milk microbiota were measured using 16S rRNA sequencing, and metabolic measurements were taken for dams and offspring at weaning (day21) and 10 days post-weaning (day31). Germ-free mice were transplanted with maternal cecal microbiota to assess the causal role of vertically transmitted microbiota. Offspring maternally exposed to antibiotics showed relatively accelerated taxonomic maturation in the gut pre- and post-weaning. Milk composition (fat, protein, hormone, microRNA, and cytokines) was unchanged but milk-derived bacteria differed between maternal treatments and contributed to offspring gut microbial structure. Male offspring were especially affected by maternal antibiotic exposure and had increased body weight, fat mass, caloric intake, and hepatic triglycerides by day 31. All but hepatic triglycerides were attenuated with maternal prebiotic co-consumption. FMT of maternal cecal matter into germ-free mice replicated male offspring body weight and hepatic outcomes. Untargeted hepatic lipidomics and network analysis revealed strong connections between several bacteria and lipid species potentially of bacterial origin that were enriched in prebiotic offspring microbiota and livers. These data confirm the role of milk microbiota in seeding offspring microbiota and implicate maternal antibiotic-associated gut microbiota as causally implicated in compromising early-life offspring hepatic metabolism that may lead to later metabolic disorders.

Background: Metabolic Syndrome (MetS) presents a global health challenge, characterized by obesity, hypertension, dyslipidemia, and insulin resistance. Despite recognition of the gut microbiome's role in metabolic health, there remains scope for defining association of unique microbes with clinical status. Unique genetic, dietary, and lifestyle factors may influence gut microbial composition and circulating metabolites, and consequently susceptibility to MetS. By identifying specific microbial and metabolomic signatures associated with MetS, we aim to uncover potential targets for reducing the disease burden.

Methods: We correlate comprehensive clinical parameters with fecal metagenomics and untargeted serum metabolomics to delineate population-specific characteristics from 142 individuals with MetS (N=97) or control (CTRL; N=45).

Results: Microbiome species-level alpha diversity was reduced in MetS compared to CTRL. After adjustment for sex, age, BMI, and intensity of statin usage, we identified 20 MetS-related species. A co-abundant network analysis revealed Eubacterium eligens, enriched in the CTRL population, with the highest node degree. Serum metabolomics identified 106 significantly differentially regulated metabolites. N-arachidonoyl dopamine (NADA), an endocannabinoid implicated in GABAergic signaling, was the most significantly altered, enriched in CTRL and correlated with E. Eligens. sPLS-DA modeling revealed that E. eligens and D. formicigenerans species cluster together with metabolites NADA and tetrahydrocorticosterone (THB), representing defining characteristics distinguishing MetS in this population.

Conclusions: Our data reveal a distinct multi-omic signature of MetS, characterized by a significant reduction in E. eligens and D. formicigenerans abundance, and in circulating NADA and THB levels.

Myocarditis is a clinical condition characterized by inflammation of the myocardium. It commonly occurs in various heart disorders and, in extreme circumstances, can be fatal. However, the effective and safe dietary strategies for alleviating myocardial inflammatory injury are currently lacking. Here we investigated the potential of daidzein (DD), a natural isoflavone found in leguminous plants, in alleviating myocardial inflammatory injury. The lipopolysaccharides (LPS)-treated C57BL/6J mice and H9c2 cardiomyocytes were employed to investigate the protective effects and mechanisms of DD against myocardial inflammation. In animal studies, DD supplementation at 50 and 100 mg/kg/day significantly alleviated the myocardial injury induced by LPS. In cell experiments, 2.5 μM DD effectively decreased LPS-induced oxidative stress, cell death, and inflammatory responses. In addition, DD mitigated the LPS-induced calcium imbalance in cardiomyocytes. Mechanistically, DD inhibited the LPS-induced myocardial inflammatory injury by targeting estrogen receptor beta (ERβ), subsequently leading to a reduction in ER stress. Furthermore, the molecular docking and experimental validation revealed that the binding pocket of DD in ERβ was highly conserved, and that the H475 and R376 residues were essential for binding DD. In summary, our results suggest that dietary DD supplementation is a promising strategy for alleviating myocardial inflammatory injury.

Dietary organosulfur compounds (OSCs) are a structurally diverse class of sulfur-containing food-derived molecules increasingly recognized for their potential interactions with endogenous sulfur and redox metabolism. Emerging evidence, largely from chemical, cellular, and preclinical studies, suggests that OSCs derived from Allium and Brassicaceae vegetables, as well as sulfur-containing amino acids, may influence hydrogen sulfide (H₂S) and reactive polysulfide biology, key components of reactive sulfur species (RSS)-mediated signaling. This review synthesizes current findings on the chemical diversity, dietary sources, processing sensitivity, and bioavailability of nutritional OSCs, with emphasis on how gastrointestinal metabolism, microbial transformation, and thiol-dependent reactions shape their biological fate. We examine proposed biochemical routes linking OSC intake to endogenous H₂S and polysulfide generation, including non-enzymatic sulfur transfer reactions and enzymatic pathways involving cystathionine β-synthase, cystathionine γ-lyase, and 3-mercaptopyruvate sulfurtransferase. Particular attention is given to protein persulfidation, mitochondrial redox regulation, and redox-sensitive transcriptional responses such as Nrf2 signaling, while acknowledging ongoing methodological and conceptual challenges in reactive sulfur species detection and interpretation. The potential implications of OSC-mediated modulation of sulfur signaling for oxidative stress responses, metabolic regulation, vascular function, neurobiology, and immune homeostasis are discussed, alongside current limitations in human evidence and key priorities for future research in nutrition-redox biology.