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Adherence to the Mediterranean diet, particularly olive oil intake, and metabolic health parameters are independently associated with SARS-CoV-2 vaccine-induced IgG responses 坚持地中海饮食,特别是橄榄油摄入量和代谢健康参数与SARS-CoV-2疫苗诱导的IgG反应独立相关
IF 2.7 Pub Date : 2026-01-21 DOI: 10.1016/j.metop.2026.100446
Dimitra Petropoulou , Dimitrios Tsilingiris , Spyridon N. Karras , Anastasios Ioannidis , Georgia Petropoulou , Antonios Chatzigeorgiou , Eva Kassi , Irene Karampela , Andriana Diamantopoulou , Konstantinos Panagiotopoulos , Maria Dalamaga

Background

Determinants of SARS-CoV-2 vaccine–induced humoral immunity extend beyond vaccination and infection history; however, the role of specific dietary patterns and metabolic health parameters has not been fully elucidated. Although very few recent studies have examined the association between Mediterranean diet (MedDiet) and immune responses to SARS-CoV-2 vaccination, evidence integrating specific food components and detailed metabolic indices in relation to vaccine-induced humoral immunity is limited. The aim of the present study was to comprehensively evaluate the associations of MedDiet, its individual components and metabolic health parameters with SARS-CoV-2 vaccine–induced IgG responses in a well-characterized population of healthcare workers.

Methods

In this cross-sectional study, 198 Greek healthcare workers (mean age 47.7 ± 11.6 years; 73.7 % female) who had received two or three BNT162b2 vaccine doses were evaluated 4–6 months post-vaccination. Demographic, clinical, anthropometric, metabolic and dietary data were collected at a single study visit. The MedDiet score and individual dietary components were assessed using a validated questionnaire. Serum SARS-CoV-2 anti–Spike (S) IgG levels were quantified using a standardized CMIA assay (Alinity i, Abbott). Multivariable linear regression analyses with log-transformed IgG titers as the dependent variable were performed using IBM SPSS Statistics.

Results

The geometric mean titer of anti–S IgG was 6373.4 AU/mL (95 % CI 5190–7820). In adjusted models, prior SARS-CoV-2 infection (p < 0.001) and receipt of three vaccine doses (p = 0.007) were the strongest correlates of higher antibody levels. Higher MedDiet adherence was independently associated with increased IgG concentrations (p = 0.027). In models including dietary components, higher olive oil (p < 0.001) and legumes consumption (p = 0.032), and lower alcohol intake (p = 0.001) were significant positive determinants. METS-IR (Metabolic Score for Insulin Resistance) and 25OHD (25 hydroxyvitamin D) status showed a significant positive association with IgG levels [p = 0.042 and p = 0.060 (of borderline statistical significance), respectively], while smoking was inversely associated (p = 0.020). Importantly, the association with olive oil intake persisted in both infection-naïve and previously infected individuals.

Conclusions

In this cross-sectional analysis, MedDiet adherence, particularly olive oil and legume consumption, and metabolic factors were associated with SARS-CoV-2 vaccine–induced IgG responses, highlighting the need for further longitudinal and interventional studies.
SARS-CoV-2疫苗诱导的体液免疫的决定因素超出了疫苗接种和感染史;然而,特定饮食模式和代谢健康参数的作用尚未完全阐明。尽管最近很少有研究调查地中海饮食(MedDiet)与对SARS-CoV-2疫苗接种的免疫反应之间的关系,但将特定食物成分和与疫苗诱导的体液免疫相关的详细代谢指标结合起来的证据有限。本研究的目的是全面评估MedDiet、其个体成分和代谢健康参数与SARS-CoV-2疫苗诱导的IgG反应在一个特征明确的医护人员人群中的关系。方法在这项横断研究中,198名希腊卫生保健工作者(平均年龄47.7±11.6岁,73.7%为女性)接种2剂或3剂BNT162b2疫苗后4-6个月进行评估。人口统计学、临床、人体测量学、代谢和饮食数据在一次研究访问中收集。MedDiet评分和个人饮食成分使用有效的问卷进行评估。采用标准化CMIA测定法(Alinity i, Abbott)定量血清SARS-CoV-2抗spike (S) IgG水平。采用IBM SPSS统计软件进行多变量线性回归分析,因变量为对数变换的IgG滴度。结果抗s IgG几何平均滴度为6373.4 AU/mL (95% CI 5190 ~ 7820)。在调整后的模型中,先前的SARS-CoV-2感染(p < 0.001)和接种三剂疫苗(p = 0.007)是抗体水平升高的最强相关性。较高的MedDiet依从性与IgG浓度升高独立相关(p = 0.027)。在包含饮食成分的模型中,高橄榄油(p < 0.001)和豆类消费(p = 0.032)以及低酒精摄入量(p = 0.001)是显著的积极决定因素。METS-IR (Metabolic Score for Insulin Resistance)和25OHD (25 hydroxyvitamin D)状态与IgG水平呈显著正相关[p = 0.042和p = 0.060(有临界统计学意义)],吸烟与IgG水平呈负相关(p = 0.020)。重要的是,在infection-naïve和先前感染的个体中,与橄榄油摄入量的关联仍然存在。在这项横断面分析中,MedDiet依从性,特别是橄榄油和豆类的摄入,以及代谢因素与SARS-CoV-2疫苗诱导的IgG反应相关,这突出了进一步的纵向和干介性研究的必要性。
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引用次数: 0
Interventions for metabolic bone disease of prematurity: A systematic review and meta-analysis 干预早产儿代谢性骨病:系统回顾和荟萃分析
IF 2.7 Pub Date : 2026-01-19 DOI: 10.1016/j.metop.2026.100445
Yazan Jumah Alalwani , Mujood Ali Alatta , Khawlah Abdullah Almana , Amal Alomari , Reem Hameed Alshammari , Ghadi Naif Alsharif , Asma Mossa Soweedi , Sofia Sharif Abualmeza , Sara Abdulrahman Alharbi , Marwa Abdullrahman Maghrabi , Kholoud Khalid Alshehri , Abdullah Alburaey , Ahmed Y. Azzam

Introduction

Metabolic bone disease of prematurity (MBDP) affects up to 30 % of very low birth weight infants; however, evidence regarding prevention and treatment strategies remains limited. We aimed to evaluate the efficacy and safety of nutritional, mechanical, and pharmacological interventions for MBDP.

Methods

Following PRISMA 2020 guidelines, we searched five databases from inception to May 5, 2025, for studies evaluating interventions for MBDP in preterm infants (<37 weeks or <1500g). Primary outcomes included MBDP incidence, bone mineral density, and safety profiles. Random-effects meta-analyses, trial sequential analysis (TSA), and GRADE assessments were conducted.

Results

Eighteen studies (1577 infants) from ten countries met inclusion criteria. Nutritional prophylaxis significantly reduced MBDP incidence by 54 % (risk ratio [RR] = 0.46, 95 % confidence interval [CI] 0.30–0.68, P-value<0.001), with early calcium/phosphorus supplementation achieving 74–84 % risk reduction. TSA confirmed conclusive evidence, with cumulative Z-score (−5.99) crossing the O'Brien-Fleming boundary at 270.9 % of required information size. Number needed to treat was five at 40 % baseline risk. Mechanical interventions improved bone mineral content by 28 % (P-value<0.01), quantitative ultrasound speed-of-sound (mean difference [MD] = 75.3 m/s, 95 % CI 45.2–105.4), and weight gain (MD = 5.11 g/kg/day, 95 % CI 3.95–6.27). Both interventions demonstrated favorable safety profiles, with mechanical protocols reporting no adverse events.

Conclusions

Nutritional prophylaxis conclusively reduces MBDP incidence, while mechanical interventions effectively improve bone mineralization. Although no studies directly evaluated combined approaches, the complementary mechanisms of nutritional and mechanical interventions suggest that optimal prevention may involve integrating both strategies. Critical gaps persist in orthopedic management, necessitating future research on fracture protocols and surgical interventions.
早产儿代谢性骨病(MBDP)影响高达30%的极低出生体重婴儿;然而,关于预防和治疗策略的证据仍然有限。我们的目的是评估营养、机械和药物干预MBDP的有效性和安全性。方法根据PRISMA 2020指南,我们检索了5个数据库,从建立到2025年5月5日,以评估早产儿(37周或1500g) MBDP干预措施的研究。主要结局包括MBDP发病率、骨密度和安全性。进行随机效应荟萃分析、试验序列分析(TSA)和GRADE评估。结果来自10个国家的18项研究(1577名婴儿)符合纳入标准。营养预防显著降低了54%的MBDP发病率(风险比[RR] = 0.46, 95%可信区间[CI] 0.30-0.68, p值<;0.001),早期补充钙/磷可使风险降低74 - 84%。TSA证实了确凿的证据,累积z分数(- 5.99)在所需信息大小的270.9%时越过O'Brien-Fleming边界。需要治疗的人数为5人,基线风险为40%。机械干预使骨矿物质含量提高28% (p值<;0.01),定量超声声速(平均差[MD] = 75.3 m/s, 95% CI 45.2-105.4),体重增加(MD = 5.11 g/kg/day, 95% CI 3.95-6.27)。两种干预措施均表现出良好的安全性,机械方案报告无不良事件。结论营养预防可有效降低MBDP发病率,机械干预可有效改善骨矿化。虽然没有研究直接评估联合方法,但营养和机械干预的互补机制表明,最佳的预防可能涉及将两种策略结合起来。在骨科治疗方面仍然存在重大差距,需要未来对骨折方案和手术干预进行研究。
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引用次数: 0
Obesity-induced cognitive impairment: Underlying mechanisms and therapeutic prospects 肥胖引起的认知障碍:潜在机制和治疗前景
IF 2.7 Pub Date : 2026-01-16 DOI: 10.1016/j.metop.2026.100444
Kai Liu , Shu Liu , Dong Wang , Hong Qiao
The prevalence of obesity continues to rise worldwide. Obesity is not only a core risk factor for chronic metabolic diseases, but also significantly associated with the risk of cognitive impairment. Obesity in middle age can cause aprosexia, cognitive disorder, dementia, hypomnesis, and increase the risk of execution decline, depression and anxiety. The underlying mechanisms involve multiple pathological pathways such as neuroinflammation, imbalance of gut microbiota-gut-brain axis, metabolic abnormalities, and imbalance of adipokines. Obesity induced chronic inflammation impairs neuroprotection by activating microglia, exacerbating β-amyloid deposition and neurodegeneration. Intestinal flora disorder impairs neuroprotection by reducing the production of short-chain fatty acids. Metabolic syndrome has synergistic damage to cerebral vascular and white matter microstructure. Genetic factors, comorbidities and ethnic differences clearly moderated the association between obesity and cognition. Among the interventions, bariatric surgery can improve executive function and memory, while lifestyle modification and drug intervention have protective effects by reducing inflammation and metabolic disorders. In the future, we need to focus on precise intervention strategies, such as developing multi-dimensional biomarkers, and optimizing obesity assessment indicators to overcome the limitations of existing studies, so as to provide a basis for phased and individualized prevention and treatment.
肥胖症的流行在世界范围内持续上升。肥胖不仅是慢性代谢性疾病的核心危险因素,而且与认知障碍风险显著相关。中年肥胖会导致失读、认知障碍、痴呆、睡眠不足,并增加执行力下降、抑郁和焦虑的风险。其潜在机制涉及多种病理途径,如神经炎症、肠道微生物-肠-脑轴失衡、代谢异常和脂肪因子失衡。肥胖引起的慢性炎症通过激活小胶质细胞,加剧β-淀粉样蛋白沉积和神经变性来损害神经保护。肠道菌群紊乱通过减少短链脂肪酸的产生而损害神经保护功能。代谢综合征对脑血管和白质微结构有协同损害。遗传因素、合并症和种族差异明显地缓和了肥胖与认知之间的关联。在这些干预措施中,减肥手术可以改善执行功能和记忆,而生活方式改变和药物干预通过减少炎症和代谢紊乱具有保护作用。未来,我们需要关注精准的干预策略,如开发多维生物标志物,优化肥胖评估指标,克服现有研究的局限性,为阶段性、个体化的预防和治疗提供依据。
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引用次数: 0
Evaluation of in vitro and in vivo antidiabetic potential of hydromethanol extract and solvent fraction of the leaves of Ajuga integrifolia (Lamiaceae) in diabetic mice models 金合欢叶氢甲醇提取物和溶剂部位对糖尿病小鼠模型的体内外抗糖尿病作用评价
IF 2.7 Pub Date : 2026-01-12 DOI: 10.1016/j.metop.2026.100443
Yalo Daba , Monas Kitessa , Kindessa Ahmed , Demis Million , Ayalew Temesgen , Meseret Amde , Tsegu Kiros , Dine Walo , Anteneh Belayneh , Jemal Abdela

Background

Diabetes mellitus is a spectrum of distinct metabolic disorders marked by sustained elevation of blood glucose levels that arises from deficiencies in either insulin action, insulin secretion, or a combination of both. Ajuga integrifolia is traditionally used to control diabetes.

Objective

To evaluate the antidiabetic effects of hydromethanol and solvent fraction extracts from the leaves of Ajuga integrifolia using in vitro and in vivo methods.

Method

The plant leaves were extracted using the maceration technique. The plant's acute oral toxicity test was evaluated according to the guidelines of the Organization for Economic Cooperation and Development. In vitro α-amylase inhibition activity of the hydromethanol and solvent fraction extracts of the leaves of Ajuga integrifolia was evaluated by using the 3, 5-dinitrosalicylic acid method.
The study examined the effects of hydromethanol and solvent fraction extracts at doses of 250, 500, and 1000 mg/kg on lowering blood glucose levels in a diabetic mouse model.

Result

An acute toxicity study of the hydromethanol extract of the leaves of the Ajuga integrifolia did not show any sign of toxicity or mortality. The greatest alpha amylase inhibition was revealed by hydromethanol extracts (57.63 ± 0.38 %) (800 μg/mL), while the n-hexane fraction (23.18 ± 0.78 %) (800 μg/mL) showed the lowest effect. The hydromethanol extract 500 mg/kg (p < 0.001) and 1000 mg/kg (p < 0.001) at 2 and 4 h significantly reduced the blood glucose level in normoglycemic mice. At 2 h, both the 500 mg/kg and 1000 mg/kg doses of hydromethanol extract significantly lowered BGL when compared to the 30-min BGL and the negative control group (P < 0.001). The hydromethanol extract and aqueous fraction showed significant (P < 0.001) antidiabetic activity at a dosage of 1000 mg/kg, resulting in a 39.2 % and 37.5 % reduction in blood glucose levels in the diabetic mice model, respectively.

Conclusion

Acute treatment with hydromethanol extract is safe and well-tolerated when administered orally. The study supported the traditional use of Ajuga integrifolia leaves for patients with diabetes.
糖尿病是一系列独特的代谢紊乱,其特征是血糖水平持续升高,这是由于胰岛素作用、胰岛素分泌不足或两者兼有而引起的。牛膝草传统上用于控制糖尿病。目的采用体外和体内实验方法,评价水曲柳叶溶剂部分提取物和氢甲醇提取物的抗糖尿病作用。方法采用浸渍法提取植物叶片。该植物的急性口服毒性试验是根据经济合作与发展组织的指导方针进行评估的。采用3,5 -二硝基水杨酸法,对水杨酸法提取的牛蒡叶的溶剂部分和氢甲醇提取物体外α-淀粉酶抑制活性进行了评价。该研究检测了250、500和1000 mg/kg剂量的氢甲醇和溶剂部分提取物对糖尿病小鼠模型的血糖水平降低的影响。结果在急性毒性试验中,水合木叶的氢甲醇提取物未显示出任何毒性和死亡迹象。氢甲醇提取物对α淀粉酶的抑制作用最大(57.63±0.38%)(800 μg/mL),正己烷提取物的抑制作用最低(23.18±0.78%)(800 μg/mL)。氢甲醇提取物500 mg/kg (p < 0.001)和1000 mg/kg (p < 0.001)在2和4 h显著降低血糖正常小鼠的血糖水平。在2小时,与30分钟BGL和阴性对照组相比,500 mg/kg和1000 mg/kg剂量的氢甲醇提取物均显著降低了BGL (P < 0.001)。在1000 mg/kg的剂量下,氢甲醇提取物和水馏分显示出显著的(P < 0.001)抗糖尿病活性,导致糖尿病小鼠模型的血糖水平分别降低39.2%和37.5%。结论口服氢甲醇提取物治疗急性急性期是安全且耐受性良好的。这项研究支持了传统的使用牛膝叶治疗糖尿病患者。
{"title":"Evaluation of in vitro and in vivo antidiabetic potential of hydromethanol extract and solvent fraction of the leaves of Ajuga integrifolia (Lamiaceae) in diabetic mice models","authors":"Yalo Daba ,&nbsp;Monas Kitessa ,&nbsp;Kindessa Ahmed ,&nbsp;Demis Million ,&nbsp;Ayalew Temesgen ,&nbsp;Meseret Amde ,&nbsp;Tsegu Kiros ,&nbsp;Dine Walo ,&nbsp;Anteneh Belayneh ,&nbsp;Jemal Abdela","doi":"10.1016/j.metop.2026.100443","DOIUrl":"10.1016/j.metop.2026.100443","url":null,"abstract":"<div><h3>Background</h3><div>Diabetes mellitus is a spectrum of distinct metabolic disorders marked by sustained elevation of blood glucose levels that arises from deficiencies in either insulin action, insulin secretion, or a combination of both. <em>Ajuga integrifolia</em> is traditionally used to control diabetes.</div></div><div><h3>Objective</h3><div>To evaluate the antidiabetic effects of hydromethanol and solvent fraction extracts from the leaves of <em>Ajuga integrifolia</em> using in vitro and in vivo methods.</div></div><div><h3>Method</h3><div>The plant leaves were extracted using the maceration technique. The plant's acute oral toxicity test was evaluated according to the guidelines of the Organization for Economic Cooperation and Development. In vitro α-amylase inhibition activity of the hydromethanol and solvent fraction extracts of the leaves of <em>Ajuga integrifolia</em> was evaluated by using the 3, 5-dinitrosalicylic acid method.</div><div>The study examined the effects of hydromethanol and solvent fraction extracts at doses of 250, 500, and 1000 mg/kg on lowering blood glucose levels in a diabetic mouse model.</div></div><div><h3>Result</h3><div>An acute toxicity study of the hydromethanol extract of the leaves of the <em>Ajuga integrifolia</em> did not show any sign of toxicity or mortality. The greatest alpha amylase inhibition was revealed by hydromethanol extracts (57.63 ± 0.38 %) (800 μg/mL), while the n-hexane fraction (23.18 ± 0.78 %) (800 μg/mL) showed the lowest effect. The hydromethanol extract 500 mg/kg (p &lt; 0.001) and 1000 mg/kg (p &lt; 0.001) at 2 and 4 h significantly reduced the blood glucose level in normoglycemic mice. At 2 h, both the 500 mg/kg and 1000 mg/kg doses of hydromethanol extract significantly lowered BGL when compared to the 30-min BGL and the negative control group (P &lt; 0.001). The hydromethanol extract and aqueous fraction showed significant (P &lt; 0.001) antidiabetic activity at a dosage of 1000 mg/kg, resulting in a 39.2 % and 37.5 % reduction in blood glucose levels in the diabetic mice model, respectively.</div></div><div><h3>Conclusion</h3><div>Acute treatment with hydromethanol extract is safe and well-tolerated when administered orally. The study supported the traditional use of <em>Ajuga integrifolia</em> leaves for patients with diabetes.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"29 ","pages":"Article 100443"},"PeriodicalIF":2.7,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cholecystectomy with jejunoileal bypass ameliorates diabetic metabolism in mice with type 2 diabetes through modulation of FXR and TGR5 signaling 胆囊切除术联合空肠回肠旁路通过调节FXR和TGR5信号通路改善2型糖尿病小鼠的糖尿病代谢
IF 2.7 Pub Date : 2025-12-22 DOI: 10.1016/j.metop.2025.100437
Haixin Yin , Weijie Chen , Xiaodong He , JianPing Zeng

Objectives

Our aim was to investigate the improvement in glucose and lipid profiles and the mechanism involving bile acid receptors FXR and TGR5 following cholecystectomy with jejunoileal bypass(CJB) in mice with type 2 diabetes mellitus (T2DM).

Methods

Twenty male mice with T2DM were randomly assigned to CJB and sham groups. We analyzed fasting blood glucose (FBG), insulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), free fatty acids (FFA), glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), and total bile acids (TBA) levels. Expression levels of the farnesoid X receptor (FXR) and G protein-coupled bile acid receptor (TGR5) in liver, muscle, and adipose tissue were assessed post-sacrifice.

Results

Despite pair-feeding, the CJB group exhibited lower body weights than the sham group at 24 weeks post-surgery (P = 0.004). The levels of FBG (P < 0.001) and insulin (P = 0.013) in the CJB group significantly decreased compared to the baseline. The intraperitoneal glucose and insulin tolerance tests demonstrated improved glucose tolerance (P = 0.004) and insulin sensitivity (P = 0.001). GLP-1 levels significantly increased (P = 0.002). The levels of TC (P < 0.001) and LDL-C (P < 0.001) were decreased, while the levels of TG (P = 0.003), HDL-C (P < 0.001), and FFA (P < 0.001) were increased at the 24th postoperative week. Furthermore, TBA concentrations were higher in the CJB group than in the control group (P < 0.001). The expression of FXR in the liver (P = 0.034), muscle (P = 0.003) and adipose tissue (P = 0.045) and that of TGR5 in the liver (P = 0.024), muscle (P = 0.026) and adipose tissue (P = 0.004) were upregulated after surgery.

Conclusions

In mice with T2DM, cholecystectomy with jejunoileal bypass modulates BA–FXR/TGR5 signaling and is associated with metabolic improvement.
目的:研究2型糖尿病(T2DM)小鼠胆囊切除术合并空肠回肠旁路术(CJB)后葡萄糖和脂质谱的改善及其与胆汁酸受体FXR和TGR5相关的机制。方法雄性T2DM小鼠20只,随机分为CJB组和假手术组。我们分析了空腹血糖(FBG)、胰岛素、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、游离脂肪酸(FFA)、胰高血糖素样肽-1 (GLP-1)、胃抑制多肽(GIP)和总胆汁酸(TBA)水平。牺牲后评估肝、肌肉和脂肪组织中法脂样X受体(FXR)和G蛋白偶联胆汁酸受体(TGR5)的表达水平。结果术后24周,CJB组体重低于假手术组(P = 0.004)。与基线相比,CJB组的FBG (P < 0.001)和胰岛素(P = 0.013)水平显著降低。腹腔内葡萄糖和胰岛素耐量试验显示葡萄糖耐量(P = 0.004)和胰岛素敏感性(P = 0.001)得到改善。GLP-1水平显著升高(P = 0.002)。术后第24周,TC (P < 0.001)、LDL-C (P < 0.001)水平降低,TG (P = 0.003)、HDL-C (P < 0.001)、FFA (P < 0.001)水平升高。此外,CJB组TBA浓度高于对照组(P < 0.001)。术后肝脏(P = 0.034)、肌肉(P = 0.003)和脂肪组织(P = 0.045)中FXR表达上调,肝脏(P = 0.024)、肌肉(P = 0.026)和脂肪组织(P = 0.004)中TGR5表达上调。结论在T2DM小鼠中,胆囊切除术联合空肠回肠旁路可调节BA-FXR /TGR5信号通路,并与代谢改善有关。
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引用次数: 0
Interactions between serum uric acid and gut microbiota: implications for metabolic health 血清尿酸和肠道菌群之间的相互作用:对代谢健康的影响
IF 2.7 Pub Date : 2025-12-22 DOI: 10.1016/j.metop.2025.100438
Nurshad Ali
Serum uric acid (SUA), the end product of purine metabolism, is a known risk factor for developing gout; however, recent evidence suggests its broader role in metabolic disorders. The gut microbiota, a complex microbial ecosystem, plays a crucial role in influencing purine metabolism and intestinal uric acid (UA) excretion. Recent findings have uncovered a two-way relationship: certain microbes can metabolize purines and UA, while elevated UA can reduce microbial diversity, alter the production of SCFAs, and compromise intestinal barrier function. These interactions are linked to obesity, insulin resistance, T2D, NAFLD, and CVD, connecting purine metabolism with overall metabolic health. This review synthesizes current experimental and clinical evidence on SUA-microbiota interactions, with an emphasis on microbial enzymes, host urate transporters, and microbial metabolites, including bile acids and SCFAs. It also discusses therapeutic implications, spanning urate-lowering drugs to microbiota-targeted strategies, including probiotics, prebiotics, and dietary modulation. Despite progress, significant gaps remain: most human studies are cross-sectional, microbial taxa influencing SUA remain inconsistent, and interindividual microbiome variability limits the translation of findings to personalized care. Future multi-omics and longitudinal approaches are necessary to elucidate causal pathways and identify biomarkers, ultimately informing innovative strategies for the prevention and treatment of metabolic diseases beyond gout.
血清尿酸(SUA),嘌呤代谢的最终产物,是一个已知的风险因素发展痛风;然而,最近的证据表明它在代谢紊乱中有更广泛的作用。肠道菌群是一个复杂的微生物生态系统,在影响嘌呤代谢和肠道尿酸排泄中起着至关重要的作用。最近的研究发现了一种双向关系:某些微生物可以代谢嘌呤和UA,而UA升高可以减少微生物多样性,改变scfa的产生,并损害肠道屏障功能。这些相互作用与肥胖、胰岛素抵抗、T2D、NAFLD和CVD有关,将嘌呤代谢与整体代谢健康联系起来。本文综述了目前sua -微生物群相互作用的实验和临床证据,重点是微生物酶、宿主尿酸转运蛋白和微生物代谢物,包括胆汁酸和SCFAs。它还讨论了治疗意义,从降低尿酸盐药物到针对微生物群的策略,包括益生菌,益生元和饮食调节。尽管取得了进展,但仍存在重大差距:大多数人类研究是横断面的,影响SUA的微生物分类群仍然不一致,个体间微生物组的可变性限制了将研究结果转化为个性化护理。未来的多组学和纵向方法对于阐明因果途径和识别生物标志物是必要的,最终为预防和治疗痛风以外的代谢性疾病提供创新策略。
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引用次数: 0
Investigating the causal roles of cholesterol and triglyceride subfractions across lipoproteins in irritable bowel syndrome: a Mendelian randomization study 调查胆固醇和甘油三酯亚组分在肠易激综合征脂蛋白中的因果作用:一项孟德尔随机研究
IF 2.7 Pub Date : 2025-12-18 DOI: 10.1016/j.metop.2025.100434
Fang Peng , Kemin Xu , Qinwen Ba , Hao Bi , Yanjun Lu

Background

Dietary composition and nutrient intake are increasingly recognised as key modulators of symptom onset and severity in a substantial subset of patients with irritable bowel syndrome (IBS). Among dietary lipids, cholesterol and triglycerides have emerged as potential contributors. Nevertheless, the causal relationship remains poorly understood, and evidence in this area remains limited. To address this gap, we conducted a Mendelian randomization (MR) study to dissect the putative causal effects of cholesterol and triglycerides on IBS risk in individuals of European ancestry.

Methods

Instrumental variables were constructed for 17 lipid traits—total cholesterol, free cholesterol, triglycerides, and 13 size-specific High-density lipoprotein(HDL), Low-density lipoprotein(LDL), and Very low-density lipoprotein (VLDL) sub-fractions—using summary-level data from the largest available genome-wide association studies (GWAS). Lipid exposures were derived from a meta-analysis of 115,082 European-ancestry individuals. IBS outcomes were ascertained in an independent cohort of 486,601 participants of European descent. Causal estimates were obtained with five complementary MR methods: inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode. Robustness was further interrogated with leave-one-out permutation, MR-Egger intercept evaluation of directional pleiotropy, and Cochran's Q assessment of heterogeneity.

Results

The MR analysis indicated that cholesterol or free cholesterol content of chylomicrons and extremely large VLDL particles were causally associated with an increased risk of developing IBS (β = 0.0679, odds ratios (OR) = 1.070, 95 % CI 1.015–1.128, P = 0.0118; and β = 0.0650, OR = 1.0672, 95 % CI 1.0179–1.1189, P = 0.0007, respectively). Conversely, equivalent increments in cholesterol or free cholesterol carried by very large HDL or very small VLDL conferred protection (β = −0.0626, OR = 0.9392, 95 % CI 0.8992–0.9810, P = 0.0047; and β = -0.0604, OR = 0.9412, 95 % CI 0.9023–0.9819, P = 0.005). Total circulating triglycerides also displayed a positive causal effect on IBS susceptibility (β = 0.0798, OR = 1.083, 95 % CI 1.0268–1.1423, P = 0.0033), with concordant directional estimates observed across the majority of lipoprotein sub-fractions.

Conclusion

Whereas triglycerides conveyed a uniformly adverse effect on IBS risk regardless of lipoprotein carrier, cholesterol displayed a net protective signal across most particle classes. This dichotomy implies that lipid-centred interventions should discriminate between the two moieties: dietary or pharmacological strategies that selectively lower triglycerides while preserving—or even augmenting—cholesterol in specific lipoprotein fractions may offer a rational, mechanistically grounded approach to IBS prevention and management.
饮食组成和营养摄入越来越被认为是肠易激综合征(IBS)患者症状发生和严重程度的关键调节因素。在膳食脂质中,胆固醇和甘油三酯已成为潜在的致病因素。然而,因果关系仍然知之甚少,这方面的证据仍然有限。为了解决这一差距,我们进行了一项孟德尔随机化(MR)研究,以剖析胆固醇和甘油三酯对欧洲血统个体肠易激综合征风险的推定因果关系。方法使用来自最大的全基因组关联研究(GWAS)的汇总数据,构建了17个脂质性状的工具变量,包括总胆固醇、游离胆固醇、甘油三酯和13个尺寸特异性高密度脂蛋白(HDL)、低密度脂蛋白(LDL)和甚低密度脂蛋白(VLDL)亚部分。脂质暴露来自对115082名欧洲血统个体的荟萃分析。IBS的结果是在一个486601名欧洲血统参与者的独立队列中确定的。因果估计通过五种互补的MR方法获得:逆方差加权(IVW)、加权中位数、MR- egger、简单模式和加权模式。鲁棒性进一步通过留一置换、MR-Egger定向多效性截距评估和Cochran’s Q异质性评估进行验证。结果磁共振分析显示,乳糜微粒胆固醇或游离胆固醇含量和超大VLDL颗粒与IBS发生风险增加有因果关系(β = 0.0679,比值比(or) = 1.070, 95% CI 1.015 ~ 1.128, P = 0.0118;和β= 0.0650,= 1.0672,95% CI 1.0179 - -1.1189, P = 0.0007)。相反,非常大的HDL或非常小的VLDL携带的胆固醇或游离胆固醇的等效增量具有保护作用(β = - 0.0626, or = 0.9392, 95% CI 0.8992-0.9810, P = 0.0047; β = -0.0604, or = 0.9412, 95% CI 0.9023-0.9819, P = 0.005)。总循环甘油三酯也显示出对IBS易感性的正因果影响(β = 0.0798, OR = 1.083, 95% CI 1.0268-1.1423, P = 0.0033),在大多数脂蛋白亚部分中观察到一致的方向估计。结论:无论何种脂蛋白载体,甘油三酯对肠易激综合征的风险均有不利影响,而胆固醇在大多数颗粒类别中均显示出净保护信号。这种二分法意味着以脂质为中心的干预应该区分两部分:饮食或药物策略选择性地降低甘油三酯,同时保留甚至增加特定脂蛋白部分的胆固醇,这可能为肠易激综合征的预防和管理提供一种合理的、机械基础的方法。
{"title":"Investigating the causal roles of cholesterol and triglyceride subfractions across lipoproteins in irritable bowel syndrome: a Mendelian randomization study","authors":"Fang Peng ,&nbsp;Kemin Xu ,&nbsp;Qinwen Ba ,&nbsp;Hao Bi ,&nbsp;Yanjun Lu","doi":"10.1016/j.metop.2025.100434","DOIUrl":"10.1016/j.metop.2025.100434","url":null,"abstract":"<div><h3>Background</h3><div>Dietary composition and nutrient intake are increasingly recognised as key modulators of symptom onset and severity in a substantial subset of patients with irritable bowel syndrome (IBS). Among dietary lipids, cholesterol and triglycerides have emerged as potential contributors. Nevertheless, the causal relationship remains poorly understood, and evidence in this area remains limited. To address this gap, we conducted a Mendelian randomization (MR) study to dissect the putative causal effects of cholesterol and triglycerides on IBS risk in individuals of European ancestry.</div></div><div><h3>Methods</h3><div>Instrumental variables were constructed for 17 lipid traits—total cholesterol, free cholesterol, triglycerides, and 13 size-specific High-density lipoprotein(HDL), Low-density lipoprotein(LDL), and Very low-density lipoprotein (VLDL) sub-fractions—using summary-level data from the largest available genome-wide association studies (GWAS). Lipid exposures were derived from a meta-analysis of 115,082 European-ancestry individuals. IBS outcomes were ascertained in an independent cohort of 486,601 participants of European descent. Causal estimates were obtained with five complementary MR methods: inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode. Robustness was further interrogated with leave-one-out permutation, MR-Egger intercept evaluation of directional pleiotropy, and Cochran's Q assessment of heterogeneity.</div></div><div><h3>Results</h3><div>The MR analysis indicated that cholesterol or free cholesterol content of chylomicrons and extremely large VLDL particles were causally associated with an increased risk of developing IBS (β = 0.0679, odds ratios (OR) = 1.070, 95 % CI 1.015–1.128, P = 0.0118; and β = 0.0650, OR = 1.0672, 95 % CI 1.0179–1.1189, P = 0.0007, respectively). Conversely, equivalent increments in cholesterol or free cholesterol carried by very large HDL or very small VLDL conferred protection (β = −0.0626, OR = 0.9392, 95 % CI 0.8992–0.9810, P = 0.0047; and β = -0.0604, OR = 0.9412, 95 % CI 0.9023–0.9819, P = 0.005). Total circulating triglycerides also displayed a positive causal effect on IBS susceptibility (β = 0.0798, OR = 1.083, 95 % CI 1.0268–1.1423, P = 0.0033), with concordant directional estimates observed across the majority of lipoprotein sub-fractions.</div></div><div><h3>Conclusion</h3><div>Whereas triglycerides conveyed a uniformly adverse effect on IBS risk regardless of lipoprotein carrier, cholesterol displayed a net protective signal across most particle classes. This dichotomy implies that lipid-centred interventions should discriminate between the two moieties: dietary or pharmacological strategies that selectively lower triglycerides while preserving—or even augmenting—cholesterol in specific lipoprotein fractions may offer a rational, mechanistically grounded approach to IBS prevention and management.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"29 ","pages":"Article 100434"},"PeriodicalIF":2.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145791759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association between serum uric acid levels and lumbar spine Z-scores in adults aged <50 years: A cross-sectional study 50岁以下成人血清尿酸水平与腰椎z评分之间的关系:一项横断面研究
IF 2.7 Pub Date : 2025-12-17 DOI: 10.1016/j.metop.2025.100435
Guanwen Sun , Yijun Zhou , Ping Zhang

Background

The prevalence of hyperuricemia is rising among young adults, yet its impact on bone metabolism remains unclear. This study investigated the association between serum uric acid levels and spinal bone mineral density in adults under 50, evaluating confounders, effect modification, and mediating pathways.

Methods

This cross-sectional study at the First People's Hospital of Changde City (January 1–December 31, 2024) included 238 individuals aged <50 years. Serum uric acid was the exposure; lumbar spine Z-score was the outcome. Multivariable linear regression assessed associations after adjusting for age, sex, creatinine, alanine aminotransferase, total cholesterol, neutrophil count, red blood cell count, waist circumference, triglycerides, and blood pressure. Stratified analyses examined effect modification; mediation analysis quantified creatinine's role.

Results

Adjusted models showed each 100 μmol/L increase in serum uric acid was associated with a 0.20 higher lumbar spine Z-score.(β = 0.002, 95 % CI: 0.000–0.004, P = 0.044). The association was significant in women (β = 0.004 per μmol/L, P = 0.009) but absent in men (β = −0.001, P = 0.712), and stronger with lower creatinine (P_interaction = 0.004) or waist circumference (P_interaction = 0.004). Creatinine mediated 49.3 % of the effect (average mediation effect = 0.161, 95 % CI: 0.004–0.562, P = 0.024; direct effect P = 0.160).

Conclusions

Higher serum uric acid levels are associated with increased spinal bone mineral density in adults under 50, mediated partly by creatinine (∼49 % of the effect), with stronger effects in women and those with better renal function and lower adiposity. These findings reposition uric acid as a potential early protector against bone loss, paving the way for sex- and metabolism-tailored interventions to prevent osteoporosis in younger populations.
背景高尿酸血症在年轻人中的患病率正在上升,但其对骨代谢的影响尚不清楚。本研究调查了50岁以下成人血清尿酸水平与脊柱骨密度之间的关系,评估了混杂因素、效应修饰和介导途径。方法于2024年1月1日至12月31日在常德市第一人民医院进行横断面研究,纳入238例50岁的个体。血清尿酸为暴露量;腰椎z评分为结果。在调整了年龄、性别、肌酐、丙氨酸转氨酶、总胆固醇、中性粒细胞计数、红细胞计数、腰围、甘油三酯和血压后,多变量线性回归评估了相关性。分层分析检验了效果的改变;中介分析量化了肌酐的作用。结果校正后的模型显示,血清尿酸每升高100 μmol/L,腰椎z评分升高0.20。(β = 0.002, 95% ci: 0.000-0.004, p = 0.044)。该相关性在女性中显著(β = 0.004 / μmol/L, P = 0.009),而在男性中不显著(β = - 0.001, P = 0.712),且与较低的肌酐(P_interaction = 0.004)或腰围(P_interaction = 0.004)相关更强。肌酐介导了49.3%的效应(平均中介效应= 0.161,95% CI: 0.004 ~ 0.562, P = 0.024;直接效应P = 0.160)。结论在50岁以下的成年人中,较高的血清尿酸水平与脊柱骨密度增加有关,部分由肌酐介导(约49%的影响),对女性和肾功能较好、脂肪较低的人的影响更大。这些发现重新定位了尿酸作为防止骨质流失的潜在早期保护器的地位,为针对性别和代谢量身定制的干预措施铺平了道路,以预防年轻人群中的骨质疏松症。
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引用次数: 0
Effectiveness of a multidisciplinary “2+N system therapy” in achieving remission and metabolic improvement in type 2 diabetes: A real-world study with 1,000 patients 多学科“2+N系统疗法”在实现2型糖尿病缓解和代谢改善方面的有效性:一项包含1000名患者的现实世界研究
IF 2.7 Pub Date : 2025-12-16 DOI: 10.1016/j.metop.2025.100436
Kejing Zeng , Bo Chen , Hejun Li , Nina Ren , Yingying Song , Minlin Liang , Yin Yang , Yali Huang , Ting Liu , Yiguang Lin , Gugen Xu

Background

Type 2 diabetes mellitus (T2DM) is a major global health challenge characterized by insulin resistance and β-cell dysfunction. Traditional treatments often fail to achieve sustained remission. This study evaluated a comprehensive “2 + N system therapy” combining Western and traditional Chinese medicine (TCM) with individualized lifestyle interventions to promote T2DM remission and improve metabolic health.

Methods

In a real-world observational study, 1000 T2DM patients (disease duration ≤5 years; BMI ≥24 kg/m2 or elevated waist circumference; preserved C-peptide) were treated with 2 + N therapy at Guangdong Second Provincial General Hospital (2015–2022). The “2” phase involved intensive insulin therapy transitioning to non-insulin agents with tailored TCM; the “N” phase included calorie-restricted low-carbohydrate diet, exercise, and psychological support. Primary outcome was diabetes remission (HbA1c < 6.5 % for ≥3 months without medication). Secondary outcomes included changes in weight, BMI, waist/hip circumference, glycemic indices, insulin resistance (HOMA-IR), β-cell function (HOMA-β), lipids, uric acid, and MRI-assessed hepatic and pancreatic fat in a subset.

Results

At 6 months, 70.5 % of participants achieved remission. Significant metabolic improvements were observed, including mean weight reduction (9.2 ± 4.3 kg), BMI decrease (3.2 ± 1.4 kg/m2), waist circumference reduction (11.0 ± 4.2 cm), and notable improvements in glycemic control (HbA1c decreased from 7.3 ± 1.3 % to 5.3 ± 0.4 %). Lipid profiles significantly improved, with triglycerides declining from 6.34 ± 3.25 to 1.39 ± 0.95 mmol/L and total cholesterol from 7.41 ± 2.20 to 3.76 ± 0.86 mmol/L. MRI analysis of a subgroup (n = 26) showed significant reductions in hepatic fat (28.8 %) and pancreatic fat (25.0 %).

Conclusions

The “2+N system therapy” demonstrated a high remission rate and extensive metabolic benefits, including substantial weight loss, improved glycemic control, enhanced insulin sensitivity, and reductions in ectopic fat. However, causality cannot be established without a control group and further prospective controlled trials are required to confirm its efficacy.
2型糖尿病(T2DM)是一种以胰岛素抵抗和β细胞功能障碍为特征的全球性健康挑战。传统的治疗方法往往不能达到持续的缓解。本研究评估了中西医结合的综合“2 + N系统疗法”与个体化生活方式干预对促进T2DM缓解和改善代谢健康的作用。方法对广东省第二总医院(2015-2022)1000例T2DM患者(病程≤5年,BMI≥24 kg/m2或腰围增高,c肽保存)进行2 + N治疗。“2”阶段为强化胰岛素治疗过渡到非胰岛素药物治疗,并结合量身定制的中药;“N”阶段包括限制卡路里的低碳水化合物饮食、锻炼和心理支持。主要结局是糖尿病缓解(HbA1c <≥3个月无药物治疗)。次要结局包括体重、BMI、腰/臀围、血糖指数、胰岛素抵抗(HOMA- ir)、β细胞功能(HOMA-β)、脂质、尿酸和mri评估的肝脏和胰腺脂肪的变化。结果6个月后,70.5%的患者获得缓解。观察到显著的代谢改善,包括平均体重减轻(9.2±4.3 kg), BMI下降(3.2±1.4 kg/m2),腰围减少(11.0±4.2 cm),血糖控制显著改善(HbA1c从7.3±1.3%降至5.3±0.4%)。脂质谱显著改善,甘油三酯从6.34±3.25降至1.39±0.95 mmol/L,总胆固醇从7.41±2.20降至3.76±0.86 mmol/L。一个亚组(n = 26)的MRI分析显示肝脏脂肪(28.8%)和胰腺脂肪(25.0%)显著减少。结论“2+N系统治疗”显示出高缓解率和广泛的代谢益处,包括显著的体重减轻、改善血糖控制、增强胰岛素敏感性和减少异位脂肪。然而,没有对照组就无法确定因果关系,需要进一步的前瞻性对照试验来证实其有效性。
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引用次数: 0
No effect of pyrroloquinoline quinone on mouse body weight and energy metabolism with the concomitant increase in mitochondrial biogenesis and antioxidant ability 吡咯喹啉醌对小鼠体重和能量代谢没有影响,同时线粒体生物发生和抗氧化能力增加
IF 2.7 Pub Date : 2025-12-11 DOI: 10.1016/j.metop.2025.100433
Lijun Zhang , Yimin Xu , Yanyan Zhao , Xiaochun Zhang , Xiangyan Liang , Zhuo Sun , Ying Zhou , Huan Liu , Jinrui Chang , Man Shi , Yufeng Zhao
Pyrroloquinoline quinone (PQQ) stimulates mitochondrial biogenesis and exhibits antioxidant properties. Since mitochondria play a crucial role in energy generation and metabolism, the present study aims to clarify whether PQQ is able to modulate energy expenditure and the development of obesity by regulating mitochondrial biogenesis. Male mice fed normal chow diet (NCD) or high fat diet (HFD) were supplemented with PQQ through drinking water for three months. Throughout this period, food and water intake, body weight, energy metabolic rate and the autonomous activity of the mice were measured. Then, the mice were sacrificed and the tissues were collected. Mitochondrial biogenesis, antioxidant capacity, and changes in gene expression were measured in liver tissue. The results showed that PQQ supplementation did not result in significant alterations in the food and water intake, body weight, and energy metabolic rate of the mice fed NCD or HFD although it significantly enhanced mitochondrial biogenesis and antioxidant capabilities of liver and promoted autonomous activity in NCD mice. Moreover, it had no impact on the adipose tissue mass in mice fed NCD or HFD. While PQQ supplementation induced the changes in metabolism-related genes such as CPT1a, SCD1, FABP1, HK2, HK3 and PGK1 in liver, it is suggested PQQ supplementation may influence lipid and glucose metabolism. However, PQQ-induced changes in hepatic gene expression and mitochondrial biogenesis are unable to alter systemic energy metabolism and adipose tissue accumulation in male mice.
吡咯喹啉醌(PQQ)刺激线粒体生物发生并表现出抗氧化特性。由于线粒体在能量产生和代谢中起着至关重要的作用,本研究旨在阐明PQQ是否能够通过调节线粒体生物发生来调节能量消耗和肥胖的发生。饲喂正常饲料(NCD)或高脂饲料(HFD)的雄性小鼠,通过饮水补充PQQ 3个月。在此期间,测量小鼠的食物和水摄入量、体重、能量代谢率和自主活动。然后处死小鼠,收集组织。在肝组织中测量线粒体生物发生、抗氧化能力和基因表达的变化。结果表明,尽管PQQ显著增强了NCD小鼠的线粒体生物发生和肝脏抗氧化能力,并促进了NCD小鼠的自主活性,但PQQ的补充并未导致NCD或HFD小鼠的食物和水摄入量、体重和能量代谢率发生显著变化。此外,它对饲喂NCD或HFD小鼠的脂肪组织质量没有影响。补充PQQ可诱导肝脏代谢相关基因如CPT1a、SCD1、FABP1、HK2、HK3和PGK1的变化,提示补充PQQ可能影响脂质和糖代谢。然而,pqq诱导的肝脏基因表达和线粒体生物发生的变化无法改变雄性小鼠的全身能量代谢和脂肪组织积累。
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