Pub Date : 2026-01-01DOI: 10.1016/j.tjnut.2025.11.020
Riya Anand , Rishav Sahil , Mukesh Jain , Ganesh Kumar Maurya , Arun S. Kharat
The gut microbiome significantly influences human health with dietary patterns, a key factor that modulates the structure and function of microbiome consortia. Plant-based diets (PBDs), including vegan and vegetarian, are linked to positive alterations in gut microbiota by stimulating the bacterial growth necessary for producing short-chain fatty acids (SCFAs). These microbial alterations help reduce inflammation, enhance gut barrier integrity, and improve metabolic health. However, not all PBDs offer beneficial effects. Recent findings highlighted that raw or minimally processed foods may transmit plant and soil-derived microbes, such as Enterobacter hormaechei, Citrobacter freundii, Raoultella ornithinolytica, and Klebsiella pneumonia into the human gut, raising concern about opportunistic infections. Although PBDs benefit in lowering the risk of chronic diseases such as obesity, diabetes, and inflammatory bowel disease, proper dietary planning is necessary to prevent potential nutrient deficiencies. Upcoming research should explore personalized nutrition, long-term microbiome shifts, and microbial transplants to improve gut health through PBDs.
{"title":"Plant-Based Diet as a Precursor to Human Gut Diversity","authors":"Riya Anand , Rishav Sahil , Mukesh Jain , Ganesh Kumar Maurya , Arun S. Kharat","doi":"10.1016/j.tjnut.2025.11.020","DOIUrl":"10.1016/j.tjnut.2025.11.020","url":null,"abstract":"<div><div>The gut microbiome significantly influences human health with dietary patterns, a key factor that modulates the structure and function of microbiome consortia. Plant-based diets (PBDs), including vegan and vegetarian, are linked to positive alterations in gut microbiota by stimulating the bacterial growth necessary for producing short-chain fatty acids (SCFAs). These microbial alterations help reduce inflammation, enhance gut barrier integrity, and improve metabolic health. However, not all PBDs offer beneficial effects. Recent findings highlighted that raw or minimally processed foods may transmit plant and soil-derived microbes, such as <em>Enterobacter hormaechei</em>, <em>Citrobacter freundii</em>, <em>Raoultella ornithinolytica</em>, and <em>Klebsiella pneumonia</em> into the human gut, raising concern about opportunistic infections. Although PBDs benefit in lowering the risk of chronic diseases such as obesity, diabetes, and inflammatory bowel disease, proper dietary planning is necessary to prevent potential nutrient deficiencies. Upcoming research should explore personalized nutrition, long-term microbiome shifts, and microbial transplants to improve gut health through PBDs.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 1","pages":"Article 101251"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.tjnut.2025.11.019
Haijun Sun , Fengyi Song , Xiaoyi Zhao , Jingdong Yin , Xin Zhang
Background
Skeletal muscle is essential for exercise and maintaining metabolic homeostasis. Myo-inositol (INS), the main isomer of inositol, has been shown to enhance glucose metabolism and skeletal muscle growth in fish. However, its effect on skeletal muscle development in mammals remains unclear.
Objectives
This research seeks to investigate the positive impacts of maternal INS intake during gestation on skeletal muscle development in the offspring using pig models.
Methods
Random allocation was performed to distribute 45 parity-matched Landrace × Yorkshire sows across 3 treatment arms: control, 0.15% INS, and 0.3% INS supplementation groups from D30 of pregnancy until farrowing. The levels of inflammation and oxidative stress in the serum (n = 8) and the composition of the gut microbiota (n = 6) of pregnant sows were evaluated. On postnatal day 1, 6 male piglets (n = 6) were selected from each of 6 litters in the control group and the 0.3% INS group. The mRNA and protein levels of key genes involved in skeletal muscle development and fiber-type composition were measured. RNA-seq analysis was then performed using the skeletal muscle of piglets. Data were analyzed using 1-way analysis of variance followed by Tukey’s multiple comparison test or an unpaired 2-tailed Student’s t-test.
Results
Dietary INS supplementation reduced inflammatory markers on D50 of pregnancy, alleviated oxidative stress in sows, and decreased the number of piglets with low birth weight by ∼60% (P = 0.01). On D50 of pregnancy, dietary supplementation with 0.3% INS reduced the relative abundance of Firmicutes from 72.92% to 60.17%, while increasing the abundance of beneficial fecal microbes in sows, such as Bacteroidetes, Fibrobacterota, Unclassified_f_Lachnospiraceae, and Prevotellaceae_NK3B31_group. Notably, maternal 0.3% INS intake increased paired box 7 protein level by 88.90% (P = 0.05) and induced muscle-fiber type transition from glycolytic to oxidative fibers in the skeletal muscle of piglets at postnatal day 1. This was evidenced by a 50.95% increase in the mRNA level of myosin heavy chain (MyHC) Ⅱa (P < 0.05) and a 55.50% decrease in the protein level of fast MyHC (P < 0.01). Transcriptomic analysis further revealed that maternal intake of 0.3% INS regulated signaling pathways associated with skeletal muscle development, such as mitogen-activated protein kinase, Notch, and Wnt.
Conclusions
INS intake was beneficial for the inflammatory and oxidative status of pregnant sows and further improved skeletal muscle development characteristics in the offspring.
{"title":"Myo-Inositol Intake during Pregnancy Alleviates Inflammation and Oxidative Stress in Sows and Improves Skeletal Muscle Development Characteristics in Offspring","authors":"Haijun Sun , Fengyi Song , Xiaoyi Zhao , Jingdong Yin , Xin Zhang","doi":"10.1016/j.tjnut.2025.11.019","DOIUrl":"10.1016/j.tjnut.2025.11.019","url":null,"abstract":"<div><h3>Background</h3><div>Skeletal muscle is essential for exercise and maintaining metabolic homeostasis. Myo-inositol (INS), the main isomer of inositol, has been shown to enhance glucose metabolism and skeletal muscle growth in fish. However, its effect on skeletal muscle development in mammals remains unclear.</div></div><div><h3>Objectives</h3><div>This research seeks to investigate the positive impacts of maternal INS intake during gestation on skeletal muscle development in the offspring using pig models.</div></div><div><h3>Methods</h3><div>Random allocation was performed to distribute 45 parity-matched Landrace × Yorkshire sows across 3 treatment arms: control, 0.15% INS, and 0.3% INS supplementation groups from D30 of pregnancy until farrowing. The levels of inflammation and oxidative stress in the serum (<em>n</em> = 8) and the composition of the gut microbiota (<em>n</em> = 6) of pregnant sows were evaluated. On postnatal day 1, 6 male piglets (<em>n</em> = 6) were selected from each of 6 litters in the control group and the 0.3% INS group. The mRNA and protein levels of key genes involved in skeletal muscle development and fiber-type composition were measured. RNA-seq analysis was then performed using the skeletal muscle of piglets. Data were analyzed using 1-way analysis of variance followed by Tukey’s multiple comparison test or an unpaired 2-tailed Student’s <em>t</em>-test.</div></div><div><h3>Results</h3><div>Dietary INS supplementation reduced inflammatory markers on D50 of pregnancy, alleviated oxidative stress in sows, and decreased the number of piglets with low birth weight by ∼60% (<em>P</em> = 0.01). On D50 of pregnancy, dietary supplementation with 0.3% INS reduced the relative abundance of Firmicutes from 72.92% to 60.17%, while increasing the abundance of beneficial fecal microbes in sows, such as Bacteroidetes, <em>Fibrobacterota</em>, <em>Unclassified_f_Lachnospiraceae</em>, and <em>Prevotellaceae_NK3B31_group.</em> Notably, maternal 0.3% INS intake increased paired box 7 protein level by 88.90% (<em>P</em> = 0.05) and induced muscle-fiber type transition from glycolytic to oxidative fibers in the skeletal muscle of piglets at postnatal day 1. This was evidenced by a 50.95% increase in the mRNA level of myosin heavy chain (MyHC) <em>Ⅱa</em> (<em>P</em> < 0.05) and a 55.50% decrease in the protein level of fast MyHC (<em>P</em> < 0.01). Transcriptomic analysis further revealed that maternal intake of 0.3% INS regulated signaling pathways associated with skeletal muscle development, such as mitogen-activated protein kinase, Notch, and Wnt.</div></div><div><h3>Conclusions</h3><div>INS intake was beneficial for the inflammatory and oxidative status of pregnant sows and further improved skeletal muscle development characteristics in the offspring.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 1","pages":"Article 101250"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.tjnut.2025.06.035
Yueqin Qiu , Shilong Liu , Li Wang , Zongyong Jiang , Xuefen Yang
Background
Early weaning may induce significant oxidative stress in piglets, potentially leading to hepatic lipid deposition and adversely affecting both metabolic health and growth.
Objectives
This study aimed to investigate the effect of bile acids (BA) supplementation on hepatic lipid metabolism in weaned piglets.
Method
Sixty-four 21-d-old weaned piglets [Duroc × (Landrace × Yorkshire); 8.21 ± 0.20 kg body weight] were randomly divided into 2 groups (8 pens per group, 2 castrated males and 2 females per pen). Piglets received either a control diet (CON) or CON supplemented with 500 mg BA per kilogram of diet (BA) for 14 d. Growth performance, hepatic lipid metabolism–related gene and protein expression, BA profiles in the liver and ileum, and ileal microbiota (16S ribosomal ribonucleic acid sequencing) were determined. Data were analyzed using 2-tailed unpaired t-tests and Kruskal-Wallis tests.
Results
Compared to the CON group, the BA group showed significant reductions in serum triglycerides (TG), serum total cholesterol, and hepatic TG (49.2%, 45.7%, and 40.7%, respectively; P < 0.05), alongside a 69.9% increase in serum high-density lipoprotein cholesterol (P < 0.05). BA supplementation significantly downregulated hepatic lipogenesis-related genes and proteins but upregulated lipolysis-related genes (P < 0.05). Hepatic lipidomics showed that BA supplementation increased phosphatidylcholine (83.0%), whereas reducing triacylglycerols (84.9%), sphingomyelins (54.7%), and diacylglycerols (73.2%) (P < 0.05). BA supplementation significantly increased hepatic conjugated BA (54.2%), cholic acid (162%), chenodeoxycholic acid (270%), and the hepatic expression of farnesoid X receptor (57.0%), small heterodimer partner (73.7%), and oxysterol 7α-hydroxylase (110%) (P < 0.05). Additionally, BA supplementation significantly decreased the ileal abundance of Lactobacillus (14.38%) but increased the abundance of Clostridium_sensu_stricto_1 (447%) and Blautia (134%) (P < 0.05). Spearman’s correlation analysis indicated that hepatic BAs and ileal microbiota had strong correlations with serum total cholesterol and TG, hepatic TG, and lipogenesis-related genes.
Conclusions
Our results suggest that BA supplementation reduces hepatic lipid deposition in weaned piglets by modulating BA metabolism and gut microbiota composition.
{"title":"Bile Acid Supplementation Reduced Hepatic Lipid Deposition and Modulated Bile Acid Metabolism and the Gut Microbiota in Weaned Piglets","authors":"Yueqin Qiu , Shilong Liu , Li Wang , Zongyong Jiang , Xuefen Yang","doi":"10.1016/j.tjnut.2025.06.035","DOIUrl":"10.1016/j.tjnut.2025.06.035","url":null,"abstract":"<div><h3>Background</h3><div>Early weaning may induce significant oxidative stress in piglets, potentially leading to hepatic lipid deposition and adversely affecting both metabolic health and growth.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate the effect of bile acids (BA) supplementation on hepatic lipid metabolism in weaned piglets.</div></div><div><h3>Method</h3><div>Sixty-four 21-d-old weaned piglets [Duroc × (Landrace × Yorkshire); 8.21 ± 0.20 kg body weight] were randomly divided into 2 groups (8 pens per group, 2 castrated males and 2 females per pen). Piglets received either a control diet (CON) or CON supplemented with 500 mg BA per kilogram of diet (BA) for 14 d. Growth performance, hepatic lipid metabolism–related gene and protein expression, BA profiles in the liver and ileum, and ileal microbiota (16S ribosomal ribonucleic acid sequencing) were determined. Data were analyzed using 2-tailed unpaired t-tests and Kruskal-Wallis tests.</div></div><div><h3>Results</h3><div>Compared to the CON group, the BA group showed significant reductions in serum triglycerides (TG), serum total cholesterol, and hepatic TG (49.2%, 45.7%, and 40.7%, respectively; <em>P</em> < 0.05), alongside a 69.9% increase in serum high-density lipoprotein cholesterol (<em>P</em> < 0.05). BA supplementation significantly downregulated hepatic lipogenesis-related genes and proteins but upregulated lipolysis-related genes (<em>P</em> < 0.05). Hepatic lipidomics showed that BA supplementation increased phosphatidylcholine (83.0%), whereas reducing triacylglycerols (84.9%), sphingomyelins (54.7%), and diacylglycerols (73.2%) (<em>P</em> < 0.05). BA supplementation significantly increased hepatic conjugated BA (54.2%), cholic acid (162%), chenodeoxycholic acid (270%), and the hepatic expression of farnesoid X receptor (57.0%), small heterodimer partner (73.7%), and oxysterol 7α-hydroxylase (110%) (<em>P</em> < 0.05). Additionally, BA supplementation significantly decreased the ileal abundance of <em>Lactobacillus</em> (14.38%) but increased the abundance of <em>Clostridium_sensu_stricto_1</em> (447%) and <em>Blautia</em> (134%) (<em>P</em> < 0.05). Spearman’s correlation analysis indicated that hepatic BAs and ileal microbiota had strong correlations with serum total cholesterol and TG, hepatic TG, and lipogenesis-related genes.</div></div><div><h3>Conclusions</h3><div>Our results suggest that BA supplementation reduces hepatic lipid deposition in weaned piglets by modulating BA metabolism and gut microbiota composition.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 1","pages":"Article 101239"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.tjnut.2025.11.012
Yiping Li , Huiwen Yao , Meiling Guo , Zhaoxiang Zeng , Xiaoliu Hu , Yan Wang , Yanmei Zhang , Cheng Chen , Rongzeng Huang , Chengwu Song , Shuna Jin
Background
Turmeric (Curcuma longa L.) is widely used as both a food and medicinal herb, exhibiting potent hypolipidemic properties. Although traditional turmeric decoctions are typically prepared with water or low-concentration alcohol, how alcohol affects the composition and bioactivity of turmeric decoction-derived exosome-like nanoparticles (TELNs) remains largely unknown.
Objectives
This study elucidates the impact of low-concentration alcohol on the physicochemical characterization and metabolites of TELNs and confirms their potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD).
Methods
This study isolated TELNs from decoctions prepared with different alcohol concentrations (0%, 10%, and 20%, respectively) using a size exclusion chromatograph. Their morphology, particle size, concentration, and zeta potential were characterized and compared. Untargeted metabolomics was further employed to analyze differences in TELNs exposed to different alcohol concentrations. A mouse model of MASLD was established through high-fat diet induction. Subsequently, the therapeutic efficacy of TELNs extracted with different alcohol concentrations was evaluated through oral administration.
Results
The results indicated that although alcohol concentration did not affect the physicochemical properties of TELNs, it significantly altered their metabolite composition. Animal experiments of MASLD showed that oral administration of TELNs in all groups could ameliorate MASLD [serum total cholesterol, low-density lipoprotein cholesterol, atherogenic index, triglycerides (TG), aspartate aminotransferase, alanine aminotransferase, liver TG, interleukin-6, and tumor necrosis factor-α, all P < 0.05] with the 0% alcohol group exhibiting the most pronounced therapeutic effect (serum low-density lipoprotein cholesterol, atherogenic index, TG, liver TG, all P < 0.05).
Conclusions
This study elucidates the impact of low-concentration alcohol on the physicochemical characterization and metabolites of TELNs and confirms their potential in treating MASLD. By integrating traditional turmeric decoction preparation methods with modern nanotechnology, this research provides new insights into the application of turmeric and the effects of alcohol on TELNs.
背景：姜黄（Curcuma longa L.）是一种广泛使用的食品和药用草药，具有有效的降血脂特性。虽然传统的姜黄煎剂通常是用水或低浓度的酒精制备的，但酒精如何影响姜黄煎剂衍生的外泌体样纳米颗粒（teln）的组成和生物活性在很大程度上仍然未知。目的：本研究阐明了低浓度酒精对teln的理化特性和代谢物的影响，并证实了其治疗代谢功能障碍相关脂肪变性肝病（MASLD）的潜力。方法：以乙醇浓度为0%、10%、20%的煎剂为原料，采用粒径隔离色谱法分离出三种不同浓度的三种煎剂。对它们的形态、粒径、浓度和zeta电位进行了表征和比较。非靶向代谢组学进一步用于分析暴露于不同酒精浓度的teln的差异。通过高脂饮食诱导建立小鼠MASLD模型。随后，采用口服给药的方法评价不同酒精浓度提取的teln的治疗效果。结果：结果表明，酒精浓度不影响teln的理化性质，但显著改变了其代谢物组成。MASLD动物实验结果显示，各组口服teln均能改善MASLD（血清TC、LDL-C、AI、TG、AST、ALT、肝脏TG、IL-6、TNF-α，均p < 0.05），其中0%酒精组效果最显著（血清LDL-C、AI、TG、肝脏TG，均p < 0.05）。结论：本研究阐明了低浓度酒精对teln的理化特性和代谢物的影响，并证实了其治疗MASLD的潜力。本研究将传统的姜黄煎剂制备方法与现代纳米技术相结合，为姜黄的应用和酒精对teln的影响提供了新的见解。
{"title":"Effects of Alcohol Extraction of Turmeric Decoction-Derived Exosome-Like Nanoparticles on Amelioration of Metabolic Dysfunction-Associated Steatotic Liver Disease","authors":"Yiping Li , Huiwen Yao , Meiling Guo , Zhaoxiang Zeng , Xiaoliu Hu , Yan Wang , Yanmei Zhang , Cheng Chen , Rongzeng Huang , Chengwu Song , Shuna Jin","doi":"10.1016/j.tjnut.2025.11.012","DOIUrl":"10.1016/j.tjnut.2025.11.012","url":null,"abstract":"<div><h3>Background</h3><div>Turmeric (<em>Curcuma longa</em> L.) is widely used as both a food and medicinal herb, exhibiting potent hypolipidemic properties. Although traditional turmeric decoctions are typically prepared with water or low-concentration alcohol, how alcohol affects the composition and bioactivity of turmeric decoction-derived exosome-like nanoparticles (TELNs) remains largely unknown.</div></div><div><h3>Objectives</h3><div>This study elucidates the impact of low-concentration alcohol on the physicochemical characterization and metabolites of TELNs and confirms their potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD).</div></div><div><h3>Methods</h3><div>This study isolated TELNs from decoctions prepared with different alcohol concentrations (0%, 10%, and 20%, respectively) using a size exclusion chromatograph. Their morphology, particle size, concentration, and zeta potential were characterized and compared. Untargeted metabolomics was further employed to analyze differences in TELNs exposed to different alcohol concentrations. A mouse model of MASLD was established through high-fat diet induction. Subsequently, the therapeutic efficacy of TELNs extracted with different alcohol concentrations was evaluated through oral administration.</div></div><div><h3>Results</h3><div>The results indicated that although alcohol concentration did not affect the physicochemical properties of TELNs, it significantly altered their metabolite composition. Animal experiments of MASLD showed that oral administration of TELNs in all groups could ameliorate MASLD [serum total cholesterol, low-density lipoprotein cholesterol, atherogenic index, triglycerides (TG), aspartate aminotransferase, alanine aminotransferase, liver TG, interleukin-6, and tumor necrosis factor-α, all <em>P</em> < 0.05] with the 0% alcohol group exhibiting the most pronounced therapeutic effect (serum low-density lipoprotein cholesterol, atherogenic index, TG, liver TG, all <em>P</em> < 0.05).</div></div><div><h3>Conclusions</h3><div>This study elucidates the impact of low-concentration alcohol on the physicochemical characterization and metabolites of TELNs and confirms their potential in treating MASLD. By integrating traditional turmeric decoction preparation methods with modern nanotechnology, this research provides new insights into the application of turmeric and the effects of alcohol on TELNs.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 1","pages":"Article 101243"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.tjnut.2025.11.014
Tao Sun , Sahil Kalia , Keith J Ou , Zackary Johnson , Xin Gen Lei
Background
Impacts of supranutritions of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and 25-hydroxyvitamin D3 on nutritional physiology of small intestines of chickens remain unclear.
Objectives
The study was to determine effects of supranutrition of DHA, EPA, and vitamin D (VD) on molecular and biochemical responses of intestinal morphology and integrity, inflammatory and redox status, and nutrient transporters in broiler chickens.
Methods
Day-old chicks (6 cages per diet, 6 chicks per cage) were fed the following: 1) corn and soybean meal basal diet (BD), 2) BD + DHA (1.5 g DHA/kg, DHA), 3) BD + DHA + EPA ( 0.3 g EPA/kg, DHA + EPA), 4) BD + DHA + VD (6000 IU/kg of diet, DHA + VD), or 5) BD + DHA + EPA + VD (DHA + EPA + VD) for 3 wk. Gut integrity and levels of messenger ribonucleic acid (mRNA), protein, and/or activity of selected biomarkers of the duodenum, jejunum, and ileum were assessed after chicks were challenged with dextran sulfate sodium.
Results
Compared with BD, DHA, DHA + EPA, and DHA + VD decreased (P < 0.05) gut penetration of administered fluorescein isothiocyanate dextran (24%‒32%) following the dextran sulfate sodium challenge. These diets enhanced (P < 0.05) a tight junction protein, villus heights (8.9%‒18%), and mRNA concentrations of glucose and amino acid transporters (18%‒144%), but decreased mRNA, protein, and/or activity levels of catalase and superoxide dismutase-1 in the duodenum. DHA + EPA + VD produced extra inhibitions of inflammatory gene expression over the combinations of 2 nutrients.
Conclusions
Feeding chickens with 1.5 g of DHA, 0.3 g of EPA, and 6,000 IU of 25-hydroxyvitamin D3 per kilogram diet exerted positive effects on intestinal morphology and integrity, inflammatory and redox status, and gene expression of glucose and amino acid transporters, but downregulated the redox systems. Our data reveal biosafety benefits and metabolic wellness in the intestines of chickens receiving the supranutrition of DHA, EPA, and VD for biofortifying their products.
背景：二十二碳六烯酸（DHA）、二十碳五烯酸（EPA）和25-羟基维生素D3 （VD）的超营养对鸡小肠营养生理的影响尚不清楚。目的：研究超营养DHA、EPA和VD对肉鸡肠道形态和完整性、炎症和氧化还原状态以及营养转运体的分子生化反应的影响。方法：日龄雏鸡（6笼/日粮，6笼/日粮）饲喂：1)玉米豆粕基础饲粮（BD）；2) BD + DHA (1.5 g DHA/kg， DHA)；3) BD + DHA+EPA (0.3 g EPA/kg, DHA+EPA)；4) BD + DHA+VD (6000 IU/kg日粮，DHA+VD)；或5)BD + DHA+EPA+VD (DHA+EPA+VD) 3周。研究了用硫酸葡聚糖钠（DSS）刺激雏鸡后，肠道完整性、十二指肠、空肠和回肠选定生物标志物的mRNA、蛋白水平和（或）活性。结果：与BD相比，DSS刺激后给予异硫氰酸荧光素葡聚糖的DHA、DHA+EPA和DHA+VD降低了肠道通透性（P < 0.05）（24-32%）。这些饲粮提高了十二指肠紧密连接蛋白、绒毛高度（8.9-18%）以及葡萄糖和氨基酸转运蛋白mRNA水平（18-144%）（P < 0.05），降低了十二指肠过氧化氢酶和超氧化物歧化酶-1 mRNA、蛋白质和（或）活性水平。DHA+EPA+VD在两种营养素的组合中产生了额外的炎症基因表达抑制。结论：每kg饲粮中添加1.5 g DHA、0.3 g EPA和6000 IU /25-羟基维生素D3对鸡的肠道形态和完整性、炎症和氧化还原状态以及葡萄糖和氨基酸转运体基因表达有积极影响，但对氧化还原系统有下调作用。我们的数据显示，在接受DHA、EPA和VD的超营养以生物强化其产品的鸡肠道中，生物安全效益和代谢健康。
{"title":"Supranutrition of n-3 Polyunsaturated Fatty Acids and 25-Hydroxyvitamin D3 Affects Intestinal Structure and Function of Broiler Chickens","authors":"Tao Sun , Sahil Kalia , Keith J Ou , Zackary Johnson , Xin Gen Lei","doi":"10.1016/j.tjnut.2025.11.014","DOIUrl":"10.1016/j.tjnut.2025.11.014","url":null,"abstract":"<div><h3>Background</h3><div>Impacts of supranutritions of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and 25-hydroxyvitamin D<sub>3</sub> on nutritional physiology of small intestines of chickens remain unclear.</div></div><div><h3>Objectives</h3><div>The study was to determine effects of supranutrition of DHA, EPA, and vitamin D (VD) on molecular and biochemical responses of intestinal morphology and integrity, inflammatory and redox status, and nutrient transporters in broiler chickens.</div></div><div><h3>Methods</h3><div>Day-old chicks (6 cages per diet, 6 chicks per cage) were fed the following: <em>1</em>) corn and soybean meal basal diet (BD), <em>2</em>) BD + DHA (1.5 g DHA/kg, DHA), <em>3</em>) BD + DHA + EPA ( 0.3 g EPA/kg, DHA + EPA), <em>4</em>) BD + DHA + VD (6000 IU/kg of diet, DHA + VD), or <em>5</em>) BD + DHA + EPA + VD (DHA + EPA + VD) for 3 wk. Gut integrity and levels of messenger ribonucleic acid (mRNA), protein, and/or activity of selected biomarkers of the duodenum, jejunum, and ileum were assessed after chicks were challenged with dextran sulfate sodium.</div></div><div><h3>Results</h3><div>Compared with BD, DHA, DHA + EPA, and DHA + VD decreased (<em>P</em> < 0.05) gut penetration of administered fluorescein isothiocyanate dextran (24%‒32%) following the dextran sulfate sodium challenge. These diets enhanced (<em>P</em> < 0.05) a tight junction protein, villus heights (8.9%‒18%), and mRNA concentrations of glucose and amino acid transporters (18%‒144%), but decreased mRNA, protein, and/or activity levels of catalase and superoxide dismutase-1 in the duodenum. DHA + EPA + VD produced extra inhibitions of inflammatory gene expression over the combinations of 2 nutrients.</div></div><div><h3>Conclusions</h3><div>Feeding chickens with 1.5 g of DHA, 0.3 g of EPA, and 6,000 IU of 25-hydroxyvitamin D<sub>3</sub> per kilogram diet exerted positive effects on intestinal morphology and integrity, inflammatory and redox status, and gene expression of glucose and amino acid transporters, but downregulated the redox systems. Our data reveal biosafety benefits and metabolic wellness in the intestines of chickens receiving the supranutrition of DHA, EPA, and VD for biofortifying their products.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 1","pages":"Article 101245"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Caloric restriction (CR) is reported to promote longevity and improve metabolism in different species, such as rodents and flies. However, limited studies have examined the effects of CR on obesity-associated psychiatric disorders and the underlying mechanisms.
Objectives
This study aimed to investigate the effects of CR on obesity-associated anxiety-like behavior in mice fed on a high-fat diet (HFD) and elucidate the underlying mechanisms.
Methods
Male C57BL/6 mice (n = 24) were randomized into the standard diet group and the HFD group (fed on an HFD for 8 wk to induce obesity). The mice in the HFD group (n = 16) were further randomized into the following 2 groups for an additional 4-wk dietary intervention: the HFD group and calorie-restricted HFD (HFCR) group (received 70% of the mean daily food intake in the previous 3 d). Mouse body weight, anxiety-like behaviors, peripheral insulin sensitivity, central insulin signaling, and fecal microbiota were assessed.
Results
HFCR effectively mitigated HFD-induced weight gain and insulin resistance, demonstrating significant reductions in final body weight (−28.0%), glucose area under the curve (−30.7%), and homeostasis model assessment of insulin resistance index (−58.8%) compared with the HFD group (P < 0.01). HFCR also significantly reduced anxiety-like behaviors in open-field and elevated plus maze tests (P < 0.05). Mechanistically, HFCR suppressed neuroinflammatory pathways by inhibiting NF-κB activation and c-Jun N-terminal kinase phosphorylation, while concurrently improving central insulin sensitivity via the insulin receptor substrate 1/Akt pathway (P < 0.05). Furthermore, HFCR remodeled the gut microbiota profile and markedly increased fecal short-chain fatty acid concentrations, with acetic acid and propionic acid levels rising by 107.7% and 57.0%, respectively (P < 0.01).
Conclusions
In summary, our data indicate that CR, even without a change in dietary composition, could attenuate HFD-induced anxiety symptoms by modulating the gut microbiota, suppressing neuroinflammation, and regulating the brain insulin signaling pathway in adult male obese mice.
{"title":"Caloric Restriction Alleviates Anxiety-Like Behaviors by Mitigating Neuroinflammation and Insulin Signaling Dysregulation in a High-Fat Diet-Induced Obesity Mouse Model","authors":"Qi Xu , Jiashuo Lu , Wenying Gao , EeMien Chan , Yali Zhang , Kunyi Huang , Anqi Xu , Xinyi Wang , Kaizhuo Sang , Xiang Gao , Xiaojun Wu","doi":"10.1016/j.tjnut.2025.11.013","DOIUrl":"10.1016/j.tjnut.2025.11.013","url":null,"abstract":"<div><h3>Background</h3><div>Caloric restriction (CR) is reported to promote longevity and improve metabolism in different species, such as rodents and flies. However, limited studies have examined the effects of CR on obesity-associated psychiatric disorders and the underlying mechanisms.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate the effects of CR on obesity-associated anxiety-like behavior in mice fed on a high-fat diet (HFD) and elucidate the underlying mechanisms.</div></div><div><h3>Methods</h3><div>Male C57BL/6 mice (<em>n</em> = 24) were randomized into the standard diet group and the HFD group (fed on an HFD for 8 wk to induce obesity). The mice in the HFD group (<em>n</em> = 16) were further randomized into the following 2 groups for an additional 4-wk dietary intervention: the HFD group and calorie-restricted HFD (HFCR) group (received 70% of the mean daily food intake in the previous 3 d). Mouse body weight, anxiety-like behaviors, peripheral insulin sensitivity, central insulin signaling, and fecal microbiota were assessed.</div></div><div><h3>Results</h3><div>HFCR effectively mitigated HFD-induced weight gain and insulin resistance, demonstrating significant reductions in final body weight (−28.0%), glucose area under the curve (−30.7%), and homeostasis model assessment of insulin resistance index (−58.8%) compared with the HFD group (<em>P</em> < 0.01). HFCR also significantly reduced anxiety-like behaviors in open-field and elevated plus maze tests (<em>P</em> < 0.05). Mechanistically, HFCR suppressed neuroinflammatory pathways by inhibiting NF-κB activation and c-Jun N-terminal kinase phosphorylation, while concurrently improving central insulin sensitivity via the insulin receptor substrate 1/Akt pathway (<em>P</em> < 0.05). Furthermore, HFCR remodeled the gut microbiota profile and markedly increased fecal short-chain fatty acid concentrations, with acetic acid and propionic acid levels rising by 107.7% and 57.0%, respectively (<em>P</em> < 0.01).</div></div><div><h3>Conclusions</h3><div>In summary, our data indicate that CR, even without a change in dietary composition, could attenuate HFD-induced anxiety symptoms by modulating the gut microbiota, suppressing neuroinflammation, and regulating the brain insulin signaling pathway in adult male obese mice.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 1","pages":"Article 101244"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.tjnut.2025.10.034
Stephen R Hennigar , James A Schairer Jr. , Alyssa M Kelley , James P McClung
Background
The iron regulatory hormone hepcidin has been shown to attenuate zinc efflux in human intestinal Caco-2 cells; however, its role in regulating intestinal zinc absorption in vivo remains unclear.
Objectives
The objective of this study was to determine the effects of hepcidin, and its upstream regulator IL-6, on intestinal zinc absorption in mice.
Methods
Six-week-old C57BL/6 mice were fed a modified AIN-93G diet containing 30 ppm zinc and 10 ppm iron for 2 wk. After the run-in diet, mice were intraperitoneally injected with saline or physiologically relevant doses of IL-6 or hepcidin peptide (n = 18/treatment). Immediately after injection, mice were given an oral gavage containing 67Zn. Tissues were collected 3, 6, and 24 h later. Dietary zinc absorption was assessed by measuring 67Zn appearance in plasma and liver by inductively coupled plasma mass spectrometry. Two-way analysis of variance with Tukey’s post-hoc comparisons were used to assess the effects of dose within a treatment (hepcidin or IL-6), time, and their interaction.
Results
Both IL-6 and hepcidin reduced plasma iron concentrations by ∼25% (P < 0.05). IL-6 (P = 0.03), but not hepcidin (P = 0.37), induced hypozincemia. Neither IL-6 nor hepcidin inhibited the appearance of 67Zn in plasma or liver of mice.
Conclusions
Findings from this in vivo study demonstrate that acute increases in IL-6, but not hepcidin, contribute to the hypozincemia observed with inflammatory and infectious diseases.
{"title":"Acute Injection of IL-6, but not Hepcidin, Results in Hypozincemia but Does not Inhibit Dietary Zinc Absorption in Mice","authors":"Stephen R Hennigar , James A Schairer Jr. , Alyssa M Kelley , James P McClung","doi":"10.1016/j.tjnut.2025.10.034","DOIUrl":"10.1016/j.tjnut.2025.10.034","url":null,"abstract":"<div><h3>Background</h3><div>The iron regulatory hormone hepcidin has been shown to attenuate zinc efflux in human intestinal Caco-2 cells; however, its role in regulating intestinal zinc absorption in vivo remains unclear.</div></div><div><h3>Objectives</h3><div>The objective of this study was to determine the effects of hepcidin, and its upstream regulator IL-6, on intestinal zinc absorption in mice.</div></div><div><h3>Methods</h3><div>Six-week-old C57BL/6 mice were fed a modified AIN-93G diet containing 30 ppm zinc and 10 ppm iron for 2 wk. After the run-in diet, mice were intraperitoneally injected with saline or physiologically relevant doses of IL-6 or hepcidin peptide (<em>n =</em> 18/treatment). Immediately after injection, mice were given an oral gavage containing <sup>67</sup>Zn. Tissues were collected 3, 6, and 24 h later. Dietary zinc absorption was assessed by measuring <sup>67</sup>Zn appearance in plasma and liver by inductively coupled plasma mass spectrometry. Two-way analysis of variance with Tukey’s post-hoc comparisons were used to assess the effects of dose within a treatment (hepcidin or IL-6), time, and their interaction.</div></div><div><h3>Results</h3><div>Both IL-6 and hepcidin reduced plasma iron concentrations by ∼25% (<em>P</em> < 0.05). IL-6 (<em>P</em> = 0.03), but not hepcidin (<em>P</em> = 0.37), induced hypozincemia. Neither IL-6 nor hepcidin inhibited the appearance of <sup>67</sup>Zn in plasma or liver of mice.</div></div><div><h3>Conclusions</h3><div>Findings from this in vivo study demonstrate that acute increases in IL-6, but not hepcidin, contribute to the hypozincemia observed with inflammatory and infectious diseases.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 1","pages":"Article 101221"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145422228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.tjnut.2025.10.039
Jantje Goerdten , Jodi Rattner , Mira Merdas , David Achaintre , Li Yuan , Paola Russo , Toomas Veidebaum , Dénes Molnár , Lauren Lissner , Stefaan De Henauw , Luis A Moreno , Krasimira Aleksandrova , Ronja Foraita , Ute Nöthlings , Pekka Keski-Rahkonen , Anna Floegel
Background
Biomarkers of food intake may improve dietary assessment. Thereby, a key concern is their reproducibility over time. In epidemiological studies, it is important to accurately estimate habitual food intake and consequent disease risk associations.
Objectives
We aimed to assess the reproducibility of 12 urinary metabolites linked to food intake and to investigate potential sources of their variation.
Methods
The analyses are based on previously identified urinary metabolites associated with dietary intake of fruits, vegetables, and chocolate in the large-scale European Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants/I.Family study. Metabolites were measured in 1788 urine samples from 599 children at study baseline (2007/2008, n = 597), at the first follow-up (2009/2010, n = 596), and at the third follow-up (2013/2014, n = 595) using high-resolution liquid chromatography–MS. Unadjusted and adjusted intraclass correlation coefficients (ICCs) were calculated for 2- and 4-y intervals. To identify sources of biomarker variability, various factors, including dietary intake, were analyzed. The amount of variance explained by each factor was quantified using the partial coefficient of determination (R2).
Results
The median ICCs were 0.27 (range: 0.11–0.54) and 0.28 (range: 0.15–0.51) over 2- and 4-y intervals, respectively. Individual factors explained a median of 17% (range: 9.8–42.4) of the variance for the 2-y interval and 14.6% (range: 8.3–43.8) for the 4-y interval. Country of residence explained the largest proportion of variance (median: 5% for the 2-y interval, 4.5% for the 4-y interval). Dietary intake explained only a variation of 0.7% (0.0–1.5) and 0.6% (0.0–1.1) for the 2- and 4-y interval, respectively.
Conclusions
The reproducibility of urinary metabolites was poor to moderate over the 2- to 4-y periods, and only part of the variability could be explained by the studied factors. Future studies should explore shorter time intervals and other sources of variation, e.g., the influence of the gut microbiome and genetic factors.
{"title":"Reproducibility and Sources of Variation of Urinary Biomarkers of Food Intake of Fruits, Vegetables, and Chocolate in European Children and Adolescents","authors":"Jantje Goerdten , Jodi Rattner , Mira Merdas , David Achaintre , Li Yuan , Paola Russo , Toomas Veidebaum , Dénes Molnár , Lauren Lissner , Stefaan De Henauw , Luis A Moreno , Krasimira Aleksandrova , Ronja Foraita , Ute Nöthlings , Pekka Keski-Rahkonen , Anna Floegel","doi":"10.1016/j.tjnut.2025.10.039","DOIUrl":"10.1016/j.tjnut.2025.10.039","url":null,"abstract":"<div><h3>Background</h3><div>Biomarkers of food intake may improve dietary assessment. Thereby, a key concern is their reproducibility over time. In epidemiological studies, it is important to accurately estimate habitual food intake and consequent disease risk associations.</div></div><div><h3>Objectives</h3><div>We aimed to assess the reproducibility of 12 urinary metabolites linked to food intake and to investigate potential sources of their variation.</div></div><div><h3>Methods</h3><div>The analyses are based on previously identified urinary metabolites associated with dietary intake of fruits, vegetables, and chocolate in the large-scale European Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants/I.Family study. Metabolites were measured in 1788 urine samples from 599 children at study baseline (2007/2008, <em>n</em> = 597), at the first follow-up (2009/2010, <em>n</em> = 596), and at the third follow-up (2013/2014, <em>n</em> = 595) using high-resolution liquid chromatography–MS. Unadjusted and adjusted intraclass correlation coefficients (ICCs) were calculated for 2- and 4-y intervals. To identify sources of biomarker variability, various factors, including dietary intake, were analyzed. The amount of variance explained by each factor was quantified using the partial coefficient of determination (<em>R</em><sup>2</sup>).</div></div><div><h3>Results</h3><div>The median ICCs were 0.27 (range: 0.11–0.54) and 0.28 (range: 0.15–0.51) over 2- and 4-y intervals, respectively. Individual factors explained a median of 17% (range: 9.8–42.4) of the variance for the 2-y interval and 14.6% (range: 8.3–43.8) for the 4-y interval. Country of residence explained the largest proportion of variance (median: 5% for the 2-y interval, 4.5% for the 4-y interval). Dietary intake explained only a variation of 0.7% (0.0–1.5) and 0.6% (0.0–1.1) for the 2- and 4-y interval, respectively.</div></div><div><h3>Conclusions</h3><div>The reproducibility of urinary metabolites was poor to moderate over the 2- to 4-y periods, and only part of the variability could be explained by the studied factors. Future studies should explore shorter time intervals and other sources of variation, e.g., the influence of the gut microbiome and genetic factors.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 1","pages":"Article 101226"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145422305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The concept of food as medicine is gaining renewed importance in oncology, with growing recognition that diet is not only supportive care but also a mechanistically informed intervention for cancer treatment. However, the biological basis linking nutrition to cancer outcomes has remained incomplete until recent advances positioned the gut microbiome as the missing link. Recent research has highlighted the gut microbiome as a key mediator, acting as a biochemical and immunological bridge that transforms dietary compounds into metabolites, influencing inflammation, immune function, and carcinogenesis. This perspective shifts nutrition from a supportive measure to an active, evidence-based strategy in cancer prevention. In this review, we highlight how specific foods, nutrients, and microbial consortia contribute to anticancer effects, while also identifying research gaps related to causality, multiomics integration, and the need to account for global dietary and genetic diversity.
{"title":"The Mediating Role of the Gut Microbiome in the Nutritional Prevention of Cancer","authors":"Priyanka Chambial , Neelam Thakur , Umesh Kumar , Saurabh Gupta","doi":"10.1016/j.tjnut.2025.101301","DOIUrl":"10.1016/j.tjnut.2025.101301","url":null,"abstract":"<div><div>The concept of food as medicine is gaining renewed importance in oncology, with growing recognition that diet is not only supportive care but also a mechanistically informed intervention for cancer treatment. However, the biological basis linking nutrition to cancer outcomes has remained incomplete until recent advances positioned the gut microbiome as the missing link. Recent research has highlighted the gut microbiome as a key mediator, acting as a biochemical and immunological bridge that transforms dietary compounds into metabolites, influencing inflammation, immune function, and carcinogenesis. This perspective shifts nutrition from a supportive measure to an active, evidence-based strategy in cancer prevention. In this review, we highlight how specific foods, nutrients, and microbial consortia contribute to anticancer effects, while also identifying research gaps related to causality, multiomics integration, and the need to account for global dietary and genetic diversity.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"156 2","pages":"Article 101301"},"PeriodicalIF":3.8,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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