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Lactobacillus plantarum TY-S8 ameliorates hyperuricemia through the regulation of gut microbiota and tryptophan metabolism in mice. 植物乳杆菌TY-S8通过调节小鼠肠道菌群和色氨酸代谢改善高尿酸血症。
IF 5.4 1区 农林科学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-03 DOI: 10.1039/d5fo04423e
Jie Li, Lixin Song, Xianfeng Liang, Jian Zhou, Jincheng Luo, Xuewei Sun, Rong Jin, Zhe Zhang

Hyperuricemia (HUA) has become a worldwide metabolic disease, which can lead to acute gout attacks, renal dysfunction, uric acid (UA) urolithiasis, and cardiovascular damage. Probiotics, known for their cost-effectiveness, minimal toxic side effects, and high safety profile, have shown potential in alleviating HUA. In the present study, the beneficial function of Lactobacillus plantarum TY-S8 on HUA and related mechanisms were comprehensively investigated by constructing a mice model of hyperuricaemia, combined with the use of microbiomics and metabolomics. Our results demonstrated that L. plantarum TY-S8 markedly lowered serum UA (SUA) concentrations by 22.41%, suppressed xanthine oxidase (XOD) activity and modulated the level of key transporters, including GLUT9, ABCG2, and NTP1. Furthermore, the pathological damage in the liver, kidney and colon of hyperuricemic mice was alleviated by the probiotics. Meanwhile, the strain upregulated the levels of occludin, a key tight junction protein, and promoted the synthesis of short-chain fatty acids (SCFAs), with a notable increase in butyric acid. Microbiome sequencing and analysis revealed that L. plantarum TY-S8 significantly increased the proportions of Lactobacillus johnsonii and Limosilactobacillus reuteri. Additionally, metabolomic analysis of fecal and blood samples indicated that the differential metabolites among the three groups were primarily indole derivatives, such as indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), and indole-3-acetaldehyde (IAAld), which are involved in the tryptophan metabolism pathway. Notably, there is a clear correlation between the key bacterial strains and these differential metabolites. At last, fecal microbiota transplantation (FMT) was performed to confirm that the ameliorative effect of L. plantarum TY-S8 on the hyperuricemic mice is primarily mediated by the regulation of gut microbiota and tryptophan metabolites. In conclusion, L. plantarum TY-S8 exerts probiotic effects on hyperuricemic mice through multiple pathways. In particular, it alleviates intestinal inflammation by regulating tryptophan metabolism, thereby effectively promoting uric acid metabolism, which highlights its potential value in the intervention of HUA.

高尿酸血症(HUA)已成为一种世界性的代谢性疾病,可导致急性痛风发作、肾功能障碍、尿酸尿石症和心血管损害。益生菌以其成本效益、毒副作用最小和安全性高而闻名,在缓解HUA方面显示出潜力。本研究通过构建小鼠高尿酸血症模型,结合微生物组学和代谢组学,全面探讨植物乳杆菌TY-S8对HUA的有益作用及其机制。结果表明,L. plantarum TY-S8显著降低血清UA (SUA)浓度22.41%,抑制黄嘌呤氧化酶(XOD)活性,调节GLUT9、ABCG2和NTP1等关键转运蛋白水平。此外,益生菌还能减轻高尿酸血症小鼠肝、肾和结肠的病理损伤。同时,该菌株上调了关键紧密连接蛋白occludin的水平,促进了短链脂肪酸(SCFAs)的合成,其中丁酸含量显著增加。微生物组测序和分析显示,L. plantarum TY-S8显著增加了约氏乳杆菌和罗伊氏乳杆菌的比例。此外,粪便和血液样本的代谢组学分析表明,三组之间的差异代谢物主要是吲哚衍生物,如吲哚-3-乙酸(IAA),吲哚-3-乳酸(ILA)和吲哚-3-乙醛(IAAld),它们参与色氨酸代谢途径。值得注意的是,关键菌株与这些差异代谢物之间存在明显的相关性。最后,通过粪便菌群移植(FMT)证实了植物乳杆菌TY-S8对高尿酸血症小鼠的改善作用主要是通过调节肠道菌群和色氨酸代谢物介导的。综上所述,植物乳杆菌TY-S8通过多种途径对高尿酸血症小鼠发挥益生菌作用。特别是通过调节色氨酸代谢来缓解肠道炎症,从而有效促进尿酸代谢,这凸显了其干预HUA的潜在价值。
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引用次数: 0
Metabolomic profiling of urinary phenolic compounds in postmenopausal women after consumption of dark chocolate, green tea, and fruit juice. 绝经后妇女食用黑巧克力、绿茶和果汁后尿中酚类化合物的代谢组学分析。
IF 5.4 1区 农林科学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-02 DOI: 10.1039/d5fo04088d
Lorena Sánchez-Martínez, Nicole Tosi, Nicola Luigi Bragazzi, Letizia Bresciani, Daniele Del Rio, María Jesús Periago, Pedro Mena, Rocío González-Barrio

Postmenopausal women are approximately twice as likely to develop cardiometabolic diseases (CMDs) as premenopausal women. Plant-based diets rich in fruits and vegetables, due to their high content of bioactive compounds such as (poly)phenols, represent a promising strategy to reduce the risk of CMDs in this population. However, the cardioprotective effects of (poly)phenols depend largely on inter-individual variability, which is strongly influenced by the gut microbiota composition. Menopause is often associated with gut dysbiosis, characterized by a reduced microbial diversity and a lower abundance of beneficial bacteria. This imbalance in the gut microbiota profile of postmenopausal women could influence (poly)phenol metabolism and, consequently, the health benefits attributed to (poly)phenol-rich food (PP-rich food) consumption. Therefore, this study aimed to assess the impact of a daily consumption of PP-rich foods (dark chocolate, green tea and fruit juice) for 2 months on the urinary phenolic profile in postmenopausal women at high cardiometabolic risk. To this end, 116 urinary phenolic metabolites were determined using UHPLC-ESI-QqQ-MS/MS. Dietary intervention with PP-rich foods led to a significant increase in the urinary excretion of phenolic metabolites derived from gut microbiota activity and phase II metabolism. Notably, there was a significant increase in the excretion of glucuronidated and/or sulfated conjugates of phenyl-γ-valerolactones, phenylvaleric acids, phenylacetic acids, benzoic acids, and urolithins. It is expected that these phenolic metabolites could be the bioactive compounds responsible for the potential beneficial effects derived from the daily intake of dark chocolate, green tea, and fruit juice on the reduction of the risk of CMDs in postmenopausal women.

绝经后妇女患心脏代谢疾病(cmd)的可能性大约是绝经前妇女的两倍。富含水果和蔬菜的植物性饮食,由于其(多)酚等生物活性化合物含量高,代表了降低这一人群中心血管疾病风险的有希望的策略。然而,(多)酚的心脏保护作用在很大程度上取决于个体间的差异,这受到肠道微生物群组成的强烈影响。更年期通常与肠道生态失调有关,其特征是微生物多样性减少和有益细菌丰度降低。绝经后妇女肠道微生物群的失衡可能会影响(多)酚代谢,从而影响富含(多)酚的食物(富含pp的食物)的健康益处。因此,本研究旨在评估每天食用富含pp的食物(黑巧克力、绿茶和果汁)2个月对绝经后心脏代谢风险高的妇女尿酚含量的影响。为此,采用UHPLC-ESI-QqQ-MS/MS对116种尿酚类代谢物进行了测定。饮食干预富含pp的食物导致尿中酚类代谢物的排泄显著增加,这些代谢物来自肠道微生物群活性和II期代谢。值得注意的是,苯-γ-戊内酯、苯戊酸、苯乙酸、苯甲酸和尿石素的葡萄糖醛酸化和/或磺化缀合物的排泄显著增加。预计这些酚类代谢物可能是生物活性化合物,负责从每天摄入黑巧克力,绿茶和果汁中获得的潜在有益效果,以降低绝经后妇女患cmd的风险。
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引用次数: 0
Rhodomyrtus tomentosa fruit alleviates hippocampal neuroinflammation and apoptosis and rescues neurogenesis to ameliorate depressive-like behaviors in CUMS-challenged mice. 毛荆果可减轻cums刺激小鼠海马神经炎症和凋亡,挽救神经发生,改善抑郁样行为。
IF 5.4 1区 农林科学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-02 DOI: 10.1039/d5fo04575d
Jingxi Zhang, Jinyuan Liang, Yan Xu, Jingyu Sun, Mengyue Zhang, Zhiyou Yang, Leigang Jin, Shaohong Chen, Chuanyin Hu, Yun-Tao Zhao

Rhodomyrtus tomentosa fruit is an edible berry with diverse bioactivities. However, its antidepressant effects remain unexplored. The purpose of this study was to evaluate the impact of Rhodomyrtus tomentosa fruit ethanol extract (RTEE) on depressive-like behaviors resulting from chronic unpredictable mild stress (CUMS) exposure in mice and to investigate the underlying molecular mechanisms. The results demonstrated that RTEE significantly ameliorated depressive-like behaviors in CUMS-challenged mice, as indicated by increased total distance traveled, velocity, and central zone entries (in the open field test), enhanced sucrose preference (in the sucrose preference test), and decreased immobility time (in the forced swim and tail suspension tests). Meanwhile, RTEE significantly reduced the number of Iba-1+ and GFAP+ cells and down-regulated COX-2, TNF-α, and IL-6 expression in the hippocampus by suppressing the TLR4/MyD88/NF-κB signaling axis, thus alleviating neuroinflammation. In addition, RTEE significantly reduced the number of TUNEL+ cells in the dentate gyrus (DG), thus attenuating hippocampal apoptosis. Moreover, RTEE significantly increased the number of DCX+ and BrdU+ cells, up-regulated PSD95 expression, and restored the AMPK/BDNF/CREB and Wnt/β-catenin signaling axes in the hippocampus, thus rescuing hippocampal neurogenesis. These findings indicated that RTEE ameliorated depressive-like behaviors in CUMS-challenged mice by alleviating hippocampal neuroinflammation and apoptosis and rescuing neurogenesis. Therefore, this study establishes a mechanistic basis for the potential of Rhodomyrtus tomentosa fruit as an innovative nutritional therapy for depression.

毛蕊红是一种具有多种生物活性的可食用浆果。然而,其抗抑郁作用仍未被探索。本研究的目的是评估红荆果乙醇提取物(RTEE)对慢性不可预测轻度应激(CUMS)暴露小鼠抑郁样行为的影响,并探讨其潜在的分子机制。结果表明,RTEE显著改善了cums挑战小鼠的抑郁样行为,增加了行走的总距离、速度和中央区域进入(在开阔场地测试中),增强了蔗糖偏好(在蔗糖偏好测试中),减少了静止时间(在强迫游泳和悬尾测试中)。同时,RTEE通过抑制TLR4/MyD88/NF-κB信号轴,显著减少海马Iba-1+、GFAP+细胞数量,下调海马COX-2、TNF-α、IL-6的表达,从而减轻神经炎症。此外,RTEE显著减少齿状回(DG)中TUNEL+细胞的数量,从而减轻海马细胞凋亡。RTEE显著增加海马DCX+和BrdU+细胞数量,上调PSD95表达,恢复海马AMPK/BDNF/CREB和Wnt/β-catenin信号轴,从而挽救海马神经发生。这些结果表明,RTEE通过减轻海马神经炎症和凋亡以及挽救神经发生来改善cums刺激小鼠的抑郁样行为。因此,本研究为毛蕊红果作为一种创新的抑郁症营养疗法的潜力奠定了机制基础。
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引用次数: 0
c9, t11-Conjugated linoleic acid supplementation improves cognitive memory in ω-3 polyunsaturated fatty acid-deficient mice. 补充c9, t11-共轭亚油酸可改善ω-3多不饱和脂肪酸缺乏小鼠的认知记忆。
IF 5.4 1区 农林科学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-02 DOI: 10.1039/d5fo03812j
Weitao Ji, Haiqin Chen, Lulu Chang, Bo Yang, Jianxin Zhao, Jiuhong Ding, Wei Chen

Long-chain polyunsaturated fatty acids (LC-PUFAs) are vital for brain health, with cis9, trans11-conjugated linoleic acid (c9, t11-CLA) showing neuroprotective effects. This study investigated the impact of c9, t11-CLA on offspring cognitive development in an ω-3 PUFA deficiency model. c9, t11-CLA supplementation during gestation and lactation improved episodic-like memory and learning ability, as evidenced by a 63% increase in novel object recognition time and reduced Morris water maze latency. c9, t11-CLA altered brain lipid profiles and promoted myelination in the prefrontal cortex of pubescent offspring mice by upregulating the protein levels of myelin-associated glycoprotein (MAG) and platelet-derived growth factor receptor alpha (PDGFRα). In addition, although proteomic KEGG analysis and western blotting verified that c9, t11-CLA supplementation appears to modulate the PTEN/AKT signaling pathway in the hippocampus, its relationship with synaptic plasticity remains speculative. Western blot validation further revealed that c9, t11-CLA supplementation enhanced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activation and trafficking through increased phosphorylation of Ca/calmodulin-dependent protein kinase II alpha (CaMKIIα) at Thr286, ultimately strengthening synaptic plasticity as evidenced by significant upregulation of postsynaptic density protein 95 (PSD95), p-CaMKIIα/CaMKIIα, and glutamate ionotropic receptor AMPA type subunit 1 (GluA1). These findings highlight the potential of c9, t11-CLA as a nutritional intervention for neurodevelopment and provide preliminary insights into the mechanisms by which c9, t11-CLA supplementation may regulate cognitive function.

长链多不饱和脂肪酸(LC-PUFAs)对大脑健康至关重要,顺式9,反式11共轭亚油酸(c9, t11-CLA)具有神经保护作用。本研究在ω-3 PUFA缺乏模型中研究了c9, t11-CLA对后代认知发育的影响。在妊娠期和哺乳期补充11- cla可改善情景样记忆和学习能力,新物体识别时间增加63%,Morris水迷宫潜伏期减少。c9, t11-CLA通过上调髓磷脂相关糖蛋白(MAG)和血小板衍生生长因子受体α (PDGFRα)的蛋白水平,改变了青春期后代小鼠的脑脂质谱,促进了前额叶皮层的髓鞘形成。此外,尽管蛋白质组学KEGG分析和western blotting验证了c9, t11-CLA的补充似乎调节了海马PTEN/AKT信号通路,但其与突触可塑性的关系仍是推测性的。Western blot验证进一步表明,c9, t11-CLA的补充通过增加Ca/钙调素依赖性蛋白激酶IIα (CaMKIIα)在Thr286位点的磷酸化,增强α-氨基-3-羟基-5-甲基-4-异唑油酸受体(AMPAR)的激活和运输,最终增强突触可塑性,这可以通过突触后密度蛋白95 (PSD95)、p-CaMKIIα/CaMKIIα和谷氨酸嗜离子受体AMPA型亚基1 (GluA1)的显著上调来证明。这些发现突出了c9, t11-CLA作为神经发育营养干预的潜力,并为c9, t11-CLA补充调节认知功能的机制提供了初步的见解。
{"title":"<i>c</i>9, <i>t</i>11-Conjugated linoleic acid supplementation improves cognitive memory in ω-3 polyunsaturated fatty acid-deficient mice.","authors":"Weitao Ji, Haiqin Chen, Lulu Chang, Bo Yang, Jianxin Zhao, Jiuhong Ding, Wei Chen","doi":"10.1039/d5fo03812j","DOIUrl":"https://doi.org/10.1039/d5fo03812j","url":null,"abstract":"<p><p>Long-chain polyunsaturated fatty acids (LC-PUFAs) are vital for brain health, with <i>cis</i>9, <i>trans</i>11-conjugated linoleic acid (<i>c</i>9, <i>t</i>11-CLA) showing neuroprotective effects. This study investigated the impact of <i>c</i>9, <i>t</i>11-CLA on offspring cognitive development in an ω-3 PUFA deficiency model. <i>c</i>9, <i>t</i>11-CLA supplementation during gestation and lactation improved episodic-like memory and learning ability, as evidenced by a 63% increase in novel object recognition time and reduced Morris water maze latency. <i>c</i>9, <i>t</i>11-CLA altered brain lipid profiles and promoted myelination in the prefrontal cortex of pubescent offspring mice by upregulating the protein levels of myelin-associated glycoprotein (MAG) and platelet-derived growth factor receptor alpha (PDGFRα). In addition, although proteomic KEGG analysis and western blotting verified that <i>c</i>9, <i>t</i>11-CLA supplementation appears to modulate the PTEN/AKT signaling pathway in the hippocampus, its relationship with synaptic plasticity remains speculative. Western blot validation further revealed that <i>c</i>9, <i>t</i>11-CLA supplementation enhanced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activation and trafficking through increased phosphorylation of Ca/calmodulin-dependent protein kinase II alpha (CaMKIIα) at Thr286, ultimately strengthening synaptic plasticity as evidenced by significant upregulation of postsynaptic density protein 95 (PSD95), p-CaMKIIα/CaMKIIα, and glutamate ionotropic receptor AMPA type subunit 1 (GluA1). These findings highlight the potential of <i>c</i>9, <i>t</i>11-CLA as a nutritional intervention for neurodevelopment and provide preliminary insights into the mechanisms by which <i>c</i>9, <i>t</i>11-CLA supplementation may regulate cognitive function.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Punicalagin is the key pomegranate polyphenol inhibiting gut microbial trimethylamine (TMA) production from L-carnitine in an in vitro human colon model. 在体外人结肠模型中,石榴多酚是抑制肠道微生物左旋肉碱产生三甲胺(TMA)的关键。
IF 5.4 1区 农林科学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-02-02 DOI: 10.1039/d5fo04781a
J E Haarhuis, M I Gamal El-Din, D Lamprinaki, P A Kroon

TMAO has been linked to various cardiometabolic diseases and all-cause mortality risk. A major dietary precursor of TMAO is L-carnitine. L-Carnitine is metabolised by microbiota to γ-butyrobetaine (γ-BB), followed by trimethylamine (TMA), and is then oxidised to TMAO in the liver. Previously, we have shown that a polyphenol-rich pomegranate extract dose-dependently inhibited the production of γ-BB and TMA from L-carnitine. Here, we further investigated the effects of the pomegranate extract and its individual constituents/metabolites (polyphenols, spray-drying agent gum Arabic, and urolithins) on the microbial metabolism of L-carnitine to γ-BB and TMA using a high-throughput in vitro model of the human colon. A small-scale, high-throughput colon model was inoculated with L-carnitine, individual constituents of the extract (2 mg mL-1), and 1% human faecal inoculum, while continuously monitoring pH. Samples were collected over 48 hours, and methylamines were quantified using LC-MS/MS with isotopically labelled internal standards. Punicalagin, but not the other constituents, inhibited the conversion of L-carnitine to γ-BB (p < 0.001) and almost completely blocked TMA production compared to the control (p < 0.003). Furthermore, including the whole pomegranate extract in the high-throughput colon model significantly reduced the pH and completely inhibited L-carnitine metabolism, suggesting that acidification may also inhibit microbial L-carnitine metabolism. Here it was shown that, of all the tested phenolic and non-phenolic components of the pomegranate extract, only punicalagin inhibited TMA production from L-carnitine, highlighting it as a promising inhibitor of TMA and potentially TMAO formation.

氧化三甲胺与各种心脏代谢疾病和全因死亡风险有关。TMAO的主要膳食前体是左旋肉碱。左旋肉碱被微生物代谢为γ-丁甜菜碱(γ-BB),然后是三甲胺(TMA),然后在肝脏氧化为TMAO。在此之前,我们已经证明富含多酚的石榴提取物可以剂量依赖性地抑制左旋肉碱产生γ-BB和TMA。在这里,我们进一步研究了石榴提取物及其单个成分/代谢物(多酚、喷雾干燥剂阿拉伯胶和尿石素)对左旋肉碱对γ-BB和TMA的微生物代谢的影响。在小规模、高通量结肠模型中接种左旋肉碱、提取物的单个成分(2 mg mL-1)和1%的人类粪便接种物,同时连续监测ph。48小时内收集样品,并使用LC-MS/MS与同位素标记的内标进行甲胺定量。与对照组相比,Punicalagin抑制了左旋肉碱向γ-BB的转化(p < 0.001),几乎完全阻断了TMA的产生(p < 0.003)。此外,在高通量结肠模型中加入全石榴提取物可显著降低pH,完全抑制左旋肉碱代谢,表明酸化也可能抑制微生物左旋肉碱代谢。研究表明,在所有测试的石榴提取物的酚类和非酚类成分中,只有石榴苷能抑制左旋肉碱产生TMA,这表明石榴苷是一种有前途的TMA和潜在的TMAO形成抑制剂。
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引用次数: 0
Multi-omics-guided discovery: yeast protein alleviates glucocorticoid-induced muscle atrophy through dual activation of IGF-1/PI3K/Akt/FOXO and CaMKK/AMPK signaling pathways. 多组学指导下的发现:酵母蛋白通过双重激活IGF-1/PI3K/Akt/FOXO和CaMKK/AMPK信号通路缓解糖皮质激素诱导的肌肉萎缩。
IF 5.4 1区 农林科学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-30 DOI: 10.1039/d5fo04912a
Yu Liang, Qiaocui Liu, Xing Zhang, Bin Li, Tao Hou

Sarcopenia, an aging-related disorder characterized by progressive loss of skeletal muscle mass and function, lacks well-defined mechanisms and specific therapeutics. This study investigated the therapeutic effects of yeast protein (YP) on dexamethasone (DEX)-induced muscle atrophy in C57BL/6J mice using transcriptomic and metabolomic approaches. High-dose (2 g per kg bodyweight) YP (H-YP) significantly ameliorated muscle histopathology, increased serum CAT and SOD activity, enhanced grip strength and hanging endurance, elevated muscle ATP and IGF-1 levels, and reduced MSTN expression (P < 0.05). Multi-omics integration revealed that H-YP improved sarcopenia primarily by modulating protein anabolism, energy metabolism, oxidative stress, lipid metabolism, and inflammatory pathways. Key upregulated targets included the Prkag3 gene and metabolites (L-histidine, L-leucine, L-tyrosine, and guanidinoacetate). Mechanistically, H-YP synergistically activated both the IGF-1/PI3K/Akt/FOXO pathway and CaMKK/AMPK axis, collectively improving insulin sensitivity, mitochondrial function, and protein homeostasis. These findings provide a strategic foundation for sarcopenia intervention.

骨骼肌减少症是一种以骨骼肌质量和功能进行性丧失为特征的衰老相关疾病,缺乏明确的机制和特异性治疗方法。本研究采用转录组学和代谢组学方法研究酵母蛋白(YP)对地塞米松(DEX)诱导的C57BL/6J小鼠肌肉萎缩的治疗作用。高剂量(2 g / kg体重)YP (H-YP)显著改善肌肉组织病理学,提高血清CAT和SOD活性,增强握力和悬吊耐力,提高肌肉ATP和IGF-1水平,降低MSTN表达(P < 0.05)。多组学整合显示,H-YP主要通过调节蛋白质合成代谢、能量代谢、氧化应激、脂质代谢和炎症途径来改善肌肉减少症。上调的关键靶点包括Prkag3基因和代谢物(l -组氨酸、l -亮氨酸、l -酪氨酸和胍乙酸酯)。在机制上,H-YP协同激活IGF-1/PI3K/Akt/FOXO通路和CaMKK/AMPK轴,共同改善胰岛素敏感性、线粒体功能和蛋白质稳态。这些发现为肌肉减少症的干预提供了战略基础。
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引用次数: 0
Association of breast milk betaine and related metabolites with neurodevelopment in 6-month-old infants: a prospective birth cohort study. 母乳甜菜碱及相关代谢物与6个月婴儿神经发育的关系:一项前瞻性出生队列研究
IF 5.4 1区 农林科学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-30 DOI: 10.1039/d5fo04631a
Qiaoli Huang, Fengfeng Guo, Haoyan Zou, Yufang Zhang, Beibei Xu, Jie Li, Yu Xiao, Siyao Zhou, Mingzhe Kou, Hexin Lin, Shanxing Gong, Xuying Tan, Fengxiang Wei, Lijun Wang

Background and aims: Currently, there is a paucity of systematic research investigating the association between betaine and its related metabolites in breast milk and infant neurodevelopment. To address this gap, this study aimed to examine the relationship between concentrations of betaine, choline, trimethylamine N-oxide (TMAO), and L-carnitine in breast milk and infant neurodevelopment. Methods: A prospective birth cohort study was conducted, enrolling 158 mother-infant pairs. Breast milk samples were collected at 42 days postpartum, and concentrations of the target metabolites were quantified using high-performance liquid chromatography-tandem mass spectrometry. Infant neurodevelopment was evaluated at 6 months of age using the "Child Developmental Scale (0-6 Years)", from which developmental quotients (DQ) across multiple domains were derived. Generalized linear models and Bayesian Kernel Machine Regression (BKMR) were employed to assess both individual and combined effects of the four metabolites on infant development. Results: Breast milk betaine levels were significantly positively associated with DQ scores in gross motor, fine motor, adaptability, and social behavior domains. Choline concentrations showed positive association with fine motor and adaptability DQ. In contrast, higher TMAO and L-carnitine levels were linked to lower adaptability and gross motor DQ, respectively. BKMR analysis identified betaine as the predominant contributor to overall developmental DQ among the four metabolites, with the strongest influence observed for the fine motor domain (posterior inclusion probability = 0.880). No significant pairwise interactions between metabolites were detected. Conclusion: This study offers comprehensive evidence regarding the relationships between breast milk levels of betaine, choline, TMAO, and L-carnitine and infant neurodevelopment at 6 months of age. These findings may inform personalized nutritional strategies during lactation to support optimal infant neurodevelopment. Clinical Trial Registry number: ChCTR2200055202.

背景与目的:目前,关于母乳中甜菜碱及其相关代谢物与婴儿神经发育之间关系的系统研究尚缺乏。为了解决这一空白,本研究旨在研究母乳中甜菜碱、胆碱、三甲胺n -氧化物(TMAO)和左肉碱浓度与婴儿神经发育之间的关系。方法:采用前瞻性出生队列研究,纳入158对母婴。产后42天采集母乳样品,采用高效液相色谱-串联质谱法测定目标代谢物浓度。在6个月大时使用“儿童发育量表(0-6岁)”评估婴儿神经发育,从中得出多个领域的发育商数(DQ)。采用广义线性模型和贝叶斯核机回归(BKMR)来评估四种代谢物对婴儿发育的单独和联合影响。结果:母乳甜菜碱水平与大运动、精细运动、适应性和社会行为领域的DQ得分显著正相关。胆碱浓度与精细运动和适应性DQ呈正相关。相比之下,较高的TMAO和左旋肉碱水平分别与较低的适应性和大运动DQ有关。BKMR分析发现,在四种代谢物中,甜菜碱是总体发育DQ的主要贡献者,对精细运动领域的影响最大(后验包含概率= 0.880)。代谢物之间未发现显著的两两相互作用。结论:本研究为母乳中甜菜碱、胆碱、氧化三甲胺和左肉碱水平与6月龄婴儿神经发育之间的关系提供了全面的证据。这些发现可能为哺乳期间的个性化营养策略提供信息,以支持最佳的婴儿神经发育。临床试验注册号:ChCTR2200055202。
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引用次数: 0
Association of fish oil supplementation with risk of incident severe non-alcoholic fatty liver disease: a prospective study of 488 888 individuals. 鱼油补充与发生严重非酒精性脂肪性肝病风险的关联:一项488888人的前瞻性研究
IF 5.4 1区 农林科学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-30 DOI: 10.1039/d5fo02448j
Youyou Zheng, Yang Ao, Xunan Lin, Xiaohui Liu, Pan Zhuang, Yu Zhang, Jingjing Jiao

Prospective evidence linking n-3 polyunsaturated fatty acid (PUFA) supplementation to non-alcoholic fatty liver disease (NAFLD) risk remains limited. In this cohort study of 488 888 UK Biobank participants, we evaluated associations of fish oil supplementation (a key source of n-3 PUFAs) with severe NAFLD incidence using Cox proportional hazards models. Mediation analysis evaluated the roles of serum metabolic and inflammatory biomarkers. Genetic interaction analyses included polymorphisms linked to n-3 PUFA metabolism. Over 12.3 years of follow-up, 5671 participants developed severe NAFLD. Fish oil supplementation was associated with a 7% lower risk of severe NAFLD (HR 0.93, 95% CI 0.87-0.99; P = 0.022). Mediation analyses revealed that C-reactive protein (CRP) (8.8% mediated), high-density lipoprotein cholesterol (HDL-C) (7.5%), and cystatin C (10.0%) partially explained this association. No significant interactions were observed between supplementation and genetic variants (all P > 0.05). These findings support the use of n-3 PUFA supplements in the primary prevention of severe NAFLD.

n-3多不饱和脂肪酸(PUFA)补充与非酒精性脂肪性肝病(NAFLD)风险之间的前瞻性证据仍然有限。在这项488888名英国生物银行参与者的队列研究中,我们使用Cox比例风险模型评估了鱼油补充剂(n-3 PUFAs的主要来源)与严重NAFLD发病率的关系。中介分析评估了血清代谢和炎症生物标志物的作用。遗传相互作用分析包括与n-3 PUFA代谢相关的多态性。在12.3年的随访中,5671名参与者出现了严重的NAFLD。鱼油补充与严重NAFLD风险降低7%相关(HR 0.93, 95% CI 0.87-0.99; P = 0.022)。中介分析显示C反应蛋白(CRP)(8.8%介导)、高密度脂蛋白胆固醇(HDL-C)(7.5%)和胱抑素C(10.0%)部分解释了这种关联。饲粮添加量与遗传变异之间无显著相互作用(均P < 0.05)。这些发现支持n-3 PUFA补充剂在严重NAFLD一级预防中的应用。
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引用次数: 0
Myricetin-3-O-galactoside in cranberries alleviates urinary tract infections in mice by inhibiting the adhesion of uropathogenic Escherichia coli CFT073. 蔓越莓杨梅素-3- o -半乳糖苷通过抑制尿路致病性大肠杆菌CFT073的粘附减轻小鼠尿路感染。
IF 5.4 1区 农林科学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-28 DOI: 10.1039/d5fo04827c
Xingyuan Wu, Zhang Qian, Weijie Zhou, Li Yue, Jianxia Sun, Weibin Bai

Urinary tract infections (UTIs) are among the most prevalent urological diseases worldwide, characterized by high morbidity and recurrence rates. Uropathogenic Escherichia coli (UPEC) is the predominant etiological agent of UTIs. It adheres to epithelial cells in the urethra or bladder via adhesins, followed by local colonization, proliferation, and induction of uroepithelial tissue damage and inflammation. However, the widespread use of antibiotics has led to increasing resistance in UPEC, posing significant challenges to the treatment of UTIs. In the present study, we successfully isolated and identified M-3-Gal as an antibacterial compound from cranberries. Research data indicated that oral administration of M-3-Gal before and after modeling in C57BL/6 mice significantly reduced bacterial loads in the urine, bladder, and kidneys of UTI mice, thereby alleviating UPEC-associated UTIs and reducing inflammatory and oxidative stress levels. In vitro experiments further revealed that M-3-Gal inhibits bacterial adhesion and invasion by suppressing the expression of bacterial adhesins, disrupting pilus structures, and downregulating the expression of cellular integrins.

尿路感染(uti)是世界上最常见的泌尿系统疾病之一,其特点是高发病率和复发率。尿路致病性大肠杆菌(UPEC)是尿路感染的主要病原。它通过黏附素附着在尿道或膀胱上皮细胞上,随后局部定植、增殖,诱导尿上皮组织损伤和炎症。然而,抗生素的广泛使用导致UPEC的耐药性增加,对uti的治疗提出了重大挑战。本研究成功地从蔓越莓中分离鉴定出M-3-Gal抗菌化合物。研究数据表明,在C57BL/6小鼠建模前后口服M-3-Gal可显著降低尿路感染小鼠尿液、膀胱和肾脏中的细菌负荷,从而缓解upec相关的尿路感染,降低炎症和氧化应激水平。体外实验进一步揭示了M-3-Gal通过抑制细菌粘附素的表达、破坏菌毛结构、下调细胞整合素的表达来抑制细菌的粘附和侵袭。
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引用次数: 0
Metabolomic analysis reveals novel ethylated hydroxytyrosol metabolites in colon cancer cells. 代谢组学分析揭示了结肠癌细胞中新的乙基化羟基酪醇代谢物。
IF 5.4 1区 农林科学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2026-01-28 DOI: 10.1039/d5fo04197j
Clara Noguera-Navarro, Carlos J García, David Auñón, Ángel Gil-Izquierdo, Silvia Montoro-García

Plants produce a diverse array of secondary metabolites, with hydroxytyrosol (HT) and its derivatives distinguished by their antioxidant and chemopreventive properties. Upon dietary consumption, native HT undergoes extensive biotransformation, initially facilitated by the gut microbiota. Increasing evidence suggests that several of these downstream products, rather than the parent molecule, are responsible for the most significant biological effects in mammalian cells. The identification of novel metabolites may reveal unknown metabolic pathways, more particularly in distinct pathological contexts such as cancer. The in vitro simulated gastrointestinal digestion (INFOGEST method) of HT, followed by bioavailability in the tumoral metabolically active intestinal Caco-2 cells (50 µM HT for 2, 4, and 6 h), was performed. Subsequently, an untargeted metabolomic analysis on the supernatant revealed novel HT-derived entities compared with water. Among these, ethoxy phenylacetic acid sulfates (4, 5), ethyl hydroxyphenylacetate acid sulfate (6) and ethoxy hydroxyphenylacetic acid or ethyl hydroxyphenylacetate glucuronide were described for the first time in a study and confirmed by MS/MS fragmentation. These accumulated ethylated forms were undetectable in non-tumoral plasma samples from HT-supplemented humans (60 mg day-1 HT for 28 days) and mice (50 mg kg-1 day-1 HT for 2 months), suggesting a tumour-specific or, at the very least, tumour-favoured biotransformation pathway. These findings not only expand the diversity of HT metabolites but also propose ethoxy-phenylacetic acid and its sulfate conjugate as potential biomarkers for cancer detection.

植物产生多种次生代谢物,羟酪醇(HT)及其衍生物以其抗氧化和化学预防特性而闻名。在饮食消耗后,天然HT经历广泛的生物转化,最初由肠道微生物群促进。越来越多的证据表明,这些下游产物中的一些,而不是母体分子,是哺乳动物细胞中最重要的生物效应的原因。新代谢物的鉴定可能揭示未知的代谢途径,特别是在不同的病理背景下,如癌症。体外模拟HT的胃肠消化(INFOGEST法),然后在肿瘤代谢活跃的肠道Caco-2细胞(50µM HT, 2、4和6小时)中进行生物利用度测定。随后,对上清进行非靶向代谢组学分析,与水相比,发现了新的ht衍生实体。其中,乙氧基苯基乙酸硫酸盐(4,5)、羟苯乙酸乙酯硫酸酯(6)、乙氧基羟基苯乙酸乙酯或羟苯乙酸乙酯葡萄糖醛酸盐是首次在研究中被描述并通过MS/MS碎片化证实。这些累积的乙基化形式在HT补充的人类(60 mg day-1 HT,持续28天)和小鼠(50 mg kg-1 day-1 HT,持续2个月)的非肿瘤血浆样本中检测不到,这表明存在肿瘤特异性或至少是肿瘤有利的生物转化途径。这些发现不仅扩大了HT代谢物的多样性,而且提出了乙氧基苯乙酸及其硫酸盐偶联物作为癌症检测的潜在生物标志物。
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引用次数: 0
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