Sophia M Goldbeck, Deiziane Vs Costa, Suemin E Yang, Caroline C Whitt, Ayesha E Tora, Cirle A Warren, Jae Hyun Shin
{"title":"Clostridioides difficile Infection in Aged Mice Decreases Memory Function, Which Can Be Protected with Alanyl-Glutamine Supplementation.","authors":"Sophia M Goldbeck, Deiziane Vs Costa, Suemin E Yang, Caroline C Whitt, Ayesha E Tora, Cirle A Warren, Jae Hyun Shin","doi":"10.1016/j.tjnut.2025.03.032","DOIUrl":"https://doi.org/10.1016/j.tjnut.2025.03.032","url":null,"abstract":"<p><strong>Background: </strong>Adults aged >65 face a higher risk of both Clostridioides difficile infection (CDI) and dementia. CDI in the elderly may exacerbate functional and cognitive impairments. Current CDI treatment options are limited. Alanyl-glutamine (AQ) is a dipeptide shown to decrease C. difficile toxin effects in vitro and in vivo.</p><p><strong>Objectives: </strong>We tested the potential benefits of AQ on the clinical outcomes and cognitive impairment in the aged mouse model of CDI treated at various timings of AQ and vancomycin treatment.</p><p><strong>Methods: </strong>C57BL/6 retired breeder (9 mo) and aged (18 mo) mice were treated with AQ-supplemented water as a 2-wk pretreatment or continuously. The mice underwent a standard CDI protocol (VPI10463) and were treated, or not, with vancomycin. Disease severity was tracked for 14 d, then novel object recognition (NOR) tests for acute memory were performed. Hippocampal tissues were assayed for molecular markers.</p><p><strong>Results: </strong>NOR testing confirmed CDI-induced cognitive impairment (P = 0.0352). AQ pretreatment had mild neuroprotective effects during CDI. Mice treated with vancomycin and continuous AQ had better clinical scores and better memory performance than vancomycin controls (P = 0.0286). Continuous AQ treatment, when used alone or paired with vancomycin, offered protection against CDI-induced cognitive impairment. The mechanism of CDI-induced memory impairment remains unclear, but infected mice had elevated synaptobrevin-2 (P = 0.0396) and neural cell adhesion molecule (P = 0.008) compared with uninfected controls on day 14 post infection.</p><p><strong>Conclusions: </strong>Our findings suggest that neuroinflammation and memory loss occur during CDI, which may be ameliorated by AQ supplementation. AQ supplementation may have both neurological and intestinal protective effects during CDI treatment.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026178","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}
Min Zhuang, Bing Wang, Yanchuan Shi, Zhongkai Zhou
{"title":"Multiorgan Regulation Mechanisms and Nutritional Intervention Strategies in Gestational Diabetes Mellitus.","authors":"Min Zhuang, Bing Wang, Yanchuan Shi, Zhongkai Zhou","doi":"10.1016/j.tjnut.2025.04.008","DOIUrl":"https://doi.org/10.1016/j.tjnut.2025.04.008","url":null,"abstract":"<p><p>Gestational diabetes mellitus (GDM) affects millions of pregnant women worldwide and leads to both short- and long-term complications for mothers and their fetuses. Managing GDM through diet, physical activity, and medical interventions can significantly reduce these risks. Studies have identified the individual and combined roles of organs regulated by placental hormones, cytokines, and gut microbiota as key pathways contributing to impaired glucose homeostasis. In this context, placental hormones mediate the crosstalk among the placenta, pancreas, and adipose tissue, stimulating endocrine pancreas adaptation and adipose tissue expansion. However, insufficient maternal physiological adaptations, such as dysregulated adipocytokines, adipokines, and oxidative stress in the pancreas, can create an environment conducive to the onset of GDM. Furthermore, gut dysbiosis implies potential mechanisms of gut-host interaction associated with the occurrence of GDM, with short-chain fatty acids possibly serving as crucial targets. Nutritional therapy is recognized as the first-line approach for managing GDM, encompassing dietary guidance and supplementation with micro- and macronutrients as well as bioactive components. Importantly, combined interventions involving multiple nutrients, such as probiotics and prebiotics with vitamins or minerals, may exert stronger beneficial effects on the prevention and treatment of GDM and its complications. This review paper discusses the regulatory role of multiorgans in GDM and the implementation of nutritional therapy for its prevention and management, along with associated complications.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026750","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}
Suman Ranjitkar, Ingrid Kvestad, Ram K Chandyo, Tor A Strand, Kjersti S Bakken, Manjeswori Ulak, Sandra Huber, Maria Averina, Merina Shrestha, Mari Hysing
{"title":"The Association between Prenatal Maternal Selenium Concentration and Neurodevelopment in Early Childhood, Results from a Mother-Child Cohort Study.","authors":"Suman Ranjitkar, Ingrid Kvestad, Ram K Chandyo, Tor A Strand, Kjersti S Bakken, Manjeswori Ulak, Sandra Huber, Maria Averina, Merina Shrestha, Mari Hysing","doi":"10.1016/j.tjnut.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.tjnut.2025.04.005","url":null,"abstract":"<p><strong>Background: </strong>Selenium (Se) is a micronutrient essential for human health and the developing brain. A few studies have demonstrated associations between maternal Se concentration and child neurodevelopment.</p><p><strong>Objectives: </strong>We aimed to describe Se status in pregnant Nepalese females and explore the association between maternal Se plasma concentration in early pregnancy and child neurodevelopment measured during early childhood in Nepalese children.</p><p><strong>Methods: </strong>The cohort study included 800 mother-infant dyads from Bhaktapur, Nepal. Blood samples from pregnant females were drawn within 15 wk of gestation and Se concentration was analyzed by inductively coupled plasma mass spectrometry. Child neurodevelopment was assessed at 6, 12, and 24 mo with the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-3). We used linear mixed models to examine the association between maternal plasma Se concentration and Bayley-3 scores, adjusted for maternal age and socioeconomic status.</p><p><strong>Results: </strong>The mean (standard deviation) maternal plasma Se concentration was 74.8 μg/L (10.4 μg/L), and 290 (36.3%) pregnant females had Se concentration indicating deficiency (<71.1 μg/L). We found no significant association between maternal Se concentration and the Bayley-3 total z-score [Coeff. 0.002 (95% confidence interval: -0.007, 0.011)], and no associations between Se concentration and any of the Bayley-3 composite and subscale scores.</p><p><strong>Conclusions: </strong>Despite a substantial proportion of pregnant females with Se deficiency, maternal Se concentration was not associated with early childhood neurodevelopment in our study cohort of healthy pregnant Nepalese females.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064092","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}
Nikkie van der Wielen, Sonja de Vries, Nadezda Khodorova, Juliane Calvez, Ilaria Minussi, Walter Gerrits, Claire Gaudichon, Daniel Tomé, Marco Mensink
{"title":"Comparison of the Dual Isotope Tracer Approach with Oro-Ileal Balance Method for Determination of Amino Acid Digestibility in Cannulated Pigs.","authors":"Nikkie van der Wielen, Sonja de Vries, Nadezda Khodorova, Juliane Calvez, Ilaria Minussi, Walter Gerrits, Claire Gaudichon, Daniel Tomé, Marco Mensink","doi":"10.1016/j.tjnut.2025.04.002","DOIUrl":"https://doi.org/10.1016/j.tjnut.2025.04.002","url":null,"abstract":"<p><strong>Background: </strong>The dual isotope tracer approach was developed as a less invasive alternative for the measurement of ileal amino acid (AA) digestibility.</p><p><strong>Objectives: </strong>This study aimed to validate the dual isotope tracer approach with the standardized oro-ileal balance method in growing pigs.</p><p><strong>Methods: </strong>Eight pigs were fitted with jugular catheters and ileal T-cannulas. On the test day, feed containing intrinsically labeled <sup>15</sup>N-milk protein and <sup>13</sup>C-spirulina was provided every half hour for 240 min. Ileal digesta and 10 jugular blood samples were collected between 0 min and 540 min. Digesta samples were analyzed for isotopic enrichment, AA, and titanium concentrations for balance method calculations. Serum AA isotopic enrichment was measured for dual stable isotope tracer calculations.</p><p><strong>Results: </strong>Using the oro-ileal balance method, the mean ileal AA digestibility of milk protein concentrate was 97.8 ± 0.59% and of spirulina 81.5 ± 2.44% (mean ± standard deviation). Lysine digestibility was specifically evaluated, as it does not transaminate. Lysine digestibility of milk protein concentrate calculated according to the dual isotope tracer approach was 88.9 ± 8.35%, 9% point lower than the value obtained with the oro-ileal method (98.1 ± 0.36, P = 0.04). Moreover, Bland-Altman analysis showed that the difference between methods was higher, with lower mean lysine digestibility.</p><p><strong>Conclusions: </strong>This study observed differences between the dual isotope tracer approach and the oro-ileal balance method for estimating lysine digestibility under the current experimental conditions with 6 pigs. This result may be due to methodological issues. Considering the use of <sup>15</sup>N protein, conclusions on other AA that do not transaminate could not be drawn.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021520","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}
Sumeet Solanki, Joseph Taranto, Ryan Rebernick, Cristina Castillo, Varun Ponnusamy, Madeline M Sykes, Scott F Leiser, Jun Hee Lee, Thomas Schmidt, Yatrik M Shah
{"title":"Low Protein Diet Exacerbates Experimental Mouse Models of Colitis through Epithelial Autonomous and Nonautonomous Mechanisms.","authors":"Sumeet Solanki, Joseph Taranto, Ryan Rebernick, Cristina Castillo, Varun Ponnusamy, Madeline M Sykes, Scott F Leiser, Jun Hee Lee, Thomas Schmidt, Yatrik M Shah","doi":"10.1016/j.tjnut.2025.03.031","DOIUrl":"https://doi.org/10.1016/j.tjnut.2025.03.031","url":null,"abstract":"<p><strong>Background: </strong>Patients with inflammatory bowel diseases (IBDs) are at risk of protein malnutrition due to increased protein loss or reduced dietary intake. The consequences of protein malnutrition on intestinal epithelial metabolism and disease progression remain poorly understood.</p><p><strong>Objectives: </strong>Given the critical role of the mechanistic target of rapamycin complex 1 (mTORC1) as an amino acid sensor and a key regulator of intestinal epithelial metabolism and homeostasis, along with the well-established influence of diet on the gut microbiota and IBD, we focused on accessing the role of dietary protein in modulating intestinal epithelial mTORC1, determine the contributions of specific amino acids such as leucine and arginine, and examine the interplay between protein malnutrition and gut microbiota driving IBD.</p><p><strong>Methods: </strong>C57BL/6 mice were assigned to a control (20% protein, n = 6), a low protein (4% protein, n = 7), or diets selectively deficient in leucine, arginine, and other essential amino acids (n = 5-6). Colitis was induced by administering 2.5% dextran sulfate sodium in drinking water for 6 d. Intestinal epithelial mTORC1 activity was assessed by immunoblotting. Gut microbiota composition was characterized using 16S sequencing, and the microbiota's role in colitis was evaluated through broad-spectrum antibiotic treatment. Disease severity was quantified by monitoring weight loss, colon shortening, histopathological damage, and inflammatory cytokine expression.</p><p><strong>Results: </strong>Protein restriction increased the severity of dextran sulfate sodium-induced colitis compared to the control diet (∗∗∗P < 0.001). Mice fed arginine-restricted diets exhibited increased colitis (∗P < 0.05). Protein restriction induced significant alterations in gut microbiota composition, and antibiotic-mediated microbiota depletion partially ameliorated colitis severity, revealing a microbiota-dependent mechanism underlying disease exacerbation.</p><p><strong>Conclusions: </strong>Our study demonstrates a complex interplay between dietary protein, epithelial mTORC1 signaling, and gut microbiota in modulating IBD pathogenesis and highlights the potential for targeted dietary strategies, including amino acid supplementation, to improve disease management in patients with IBD.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013055","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}
{"title":"High-Cellulose Diet Ameliorates Cognitive Impairment by Modulating Gut Microbiota and Metabolic Pathways in Mice.","authors":"Moeka Tanabe, Kazuo Kunisawa, Imari Saito, Haruto Ojika, Kuniaki Saito, Toshitaka Nabeshima, Akihiro Mouri","doi":"10.1016/j.tjnut.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.tjnut.2025.04.004","url":null,"abstract":"<p><strong>Background: </strong>Nutrition is a key factor in cognitive function, and safe dietary interventions are promising to prevent cognitive impairment in pediatric psychiatric disorders. We previously demonstrated that childhood social isolation (SI) stress affects colonic function, leading to cognitive impairment. Cellulose, an insoluble dietary fiber, shows benefits to intestinal health, but its potential impact on cognitive impairment has not been explored.</p><p><strong>Objectives: </strong>This study investigated whether a high-cellulose diet ameliorates cognitive impairment induced by SI through modulation of gut microbiota and metabolic pathways.</p><p><strong>Methods: </strong>C57BL/6J male mice (3 wk old; n = 10-15/group) were randomly divided into 2 groups: individually housed (SI) group and housed 5 mice per cage (group-housed) group. Each group received either a normal diet (5% cellulose) or a high-cellulose diet (30% cellulose) for 5 wk daily until the end of the behavioral testing. We evaluated behavior abnormalities, gut microbiota composition, and metabolites, and performed 2-way analysis of variance.</p><p><strong>Results: </strong>Intake of a high-cellulose diet ameliorated cognitive impairment, including decreased time spent in a novel location of SI mice in novel object location test (NOLT; +30%; P < 0.01) with reduction of Iba-1 positive cells, microglia, in the hippocampus (-33%; P < 0.05). The high-cellulose diet indicated a significant difference in gut microbiota clustering plots (P < 0.01) and enhanced the variation in malate-aspartate shuttle pathways in SI mice (P < 0.01). Notably, fecal microbiota transplantation (FMT) from SI mice fed a high-cellulose diet after antibiotic treatment, replicated amelioration of cognitive impairment in NOLT (+46%; P < 0.01). Additionally, the FMT replicated a decrease of Iba-1 positive cells indicating suppressed hippocampal microglial activation (-52%; P < 0.01), and enhanced the variation in malate-aspartate shuttle pathways (P < 0.01).</p><p><strong>Conclusions: </strong>These findings suggest that a high-cellulose diet may ameliorate pediatric-specific cognitive impairment through modulation of the gut microbiota and metabolic pathways.</p>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144021790","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}
{"title":"Epidemiologic Risk and Prevention and Interventions in Parkinson Disease: From a Nutrition-Based Perspective","authors":"Fan Zhang , Yu-Xian Liu , Yun-Yue Zhu , Qiu-Yan Yu , Samwel Sylvester Msigwa , Zhi-Hai Zeng , Xiong Zhang , Hong-Mei Wu , Jian-Hong Zhu","doi":"10.1016/j.tjnut.2025.01.028","DOIUrl":"10.1016/j.tjnut.2025.01.028","url":null,"abstract":"<div><div>Parkinson disease (PD) is a prevalent neurodegenerative disorder associated with aging. Current treatments for PD primarily focus on alleviating symptoms rather than altering the progression of the disease. The sporadic form of PD, which accounts for most cases, is thought to arise from a complex interaction between genetic predispositions and environmental factors. This review aimed to examine epidemiologic evidence regarding nutrition-related exposure factors and their associations with risk of developing PD. We proposed a tentative conclusion for each factor based on the available evidence. These associations may vary by gender and depend on dietary intake patterns and adherence. We also reviewed clinical trials on nutrition-related interventions for PD symptoms and progression. Future clinical trials may benefit from combining nutrition factors in intervention and testing within single-gender cohorts or subgroups defined by epidemiologic outcomes.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"155 4","pages":"Pages 1019-1030"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123052","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}
Julia A Vitagliano , Jill R Kavanaugh , Boone Gorges , Xiaokang Fu , Kieran Todd , Carly E Milliren , Amanda Raffoul , S Bryn Austin
{"title":"The STRIPED Dietary Supplement Label Explorer: A Tool to Identify Supplements Sold with Weight-Loss, Muscle-Building, and Cleanse/Detox Claims","authors":"Julia A Vitagliano , Jill R Kavanaugh , Boone Gorges , Xiaokang Fu , Kieran Todd , Carly E Milliren , Amanda Raffoul , S Bryn Austin","doi":"10.1016/j.tjnut.2025.02.007","DOIUrl":"10.1016/j.tjnut.2025.02.007","url":null,"abstract":"<div><h3>Background</h3><div>Limited federal premarket oversight over United States-sold dietary supplements impedes consumer safety and product efficacy. The Dietary Supplement Label Database (DSLD) was created to increase publicly available information on United States-sold dietary supplements. Building on what the DSLD was designed to provide, we aimed to create a comprehensive database that can facilitate searches on supplements sold with weight loss, muscle building, and cleanse/detox claims, supplement categories previously flagged for misleading claims and containing toxic ingredients.</div></div><div><h3>Objectives</h3><div>This study aims to leverage publicly available DSLD Application Programming Interface (API) to develop an easy-to-use tool to classify DSLD supplement labels with weight loss, muscle building and cleanse/detox claims.</div></div><div><h3>Methods</h3><div>A 4-step categorization methodology was used to develop the tool: <em>1</em>) create reference standard database by deductively coding claims (weight loss, muscle building, and cleanse/detox) on 5000 DSLD labels; <em>2</em>) develop 3 systematic heuristics (1 per claim) and refine heuristics as assessed by recall, specificity, precision, negative predictive value, F1 Score, and accuracy; <em>3</em>) develop multimodal deep learning model as an additional method to identify the 3 claims; and <em>4</em>) compare models’ performance using the receiver operating characteristic (ROC) curve and efficiency analyses (i.e. hours of human labor taken to develop each model).</div></div><div><h3>Results</h3><div>Of the 4745 DSLD labels included in the reference standard database, 4.2% were defined using the criteria as weight loss, 6.3% muscle building, and 3.0% cleanse/detox. Three systematic heuristics for each claim were refined 4 times, with pass 4 exceeding prior passes’ performances. ROC curve analyses indicated that systematic heuristic performed significantly better (<em>P</em> < 0.05) than the multimodal deep learning model at classifying cleanse/detox labels, yet efficiency analyses found systematic heuristics less efficient (110 compared with 30 h).</div></div><div><h3>Conclusions</h3><div>Our findings illustrate the feasibility of using the DSLD API to create a tool that classifies weight loss, muscle building, and cleanse/detox labels using our supplement label categorization methodology. This publicly available tool, STRIPED Dietary Supplement Label Explorer<em>,</em> may be used to support future research and the monitoring of claims on dietary supplement labels.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"155 4","pages":"Pages 1258-1267"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425670","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}
Xinyu Zhu , Allison C Sylvetsky , Marjorie L McCullough , Jean A Welsh , Terryl J Hartman , Erin P Ferranti , Caroline Y Um
{"title":"Association of Low-Calorie Sweeteners with Selected Circulating Biomarkers of Intestinal Permeability in the Cancer Prevention Study-3 Diet Assessment Substudy","authors":"Xinyu Zhu , Allison C Sylvetsky , Marjorie L McCullough , Jean A Welsh , Terryl J Hartman , Erin P Ferranti , Caroline Y Um","doi":"10.1016/j.tjnut.2025.02.022","DOIUrl":"10.1016/j.tjnut.2025.02.022","url":null,"abstract":"<div><h3>Background</h3><div>Low-calorie sweeteners (LCSs) are popular sugar substitutes and have been shown to alter the gut microbiota, which raises concerns about potential impacts on intestinal permeability.</div></div><div><h3>Objectives</h3><div>This study aimed to examine cross-sectional associations between LCS consumption and circulating biomarkers of intestinal permeability.</div></div><div><h3>Methods</h3><div>We analyzed data from 572 United States adults participating in the Cancer Prevention Study-3 Diet Assessment Substudy who provided ≤2 fasting blood samples, collected 6 mo apart, to measure biomarkers of intestinal permeability including antibodies to flagellin (anti-flagellin), lipopolysaccharide (anti-LPS), and total antibodies; and ≤6 24-h dietary recalls, collected over the course of 12 mo, to estimate average intake of LCS including aspartame, sucralose, acesulfame-potassium, and saccharin. Multivariable linear regression, adjusted for sociodemographic characteristics, lifestyle factors, and medical history, was used to examine associations between LCS consumption and levels of intestinal permeability biomarkers by comparing mean differences in biomarkers among lower (>0 to ≤50th percentile) (<em>n</em> = 158) and higher (>50th percentile) LCS consumers (<em>n</em> = 157) than nonconsumers. A linear trend across nonconsumers and the 2 consumption categories was evaluated using a continuous variable based on the median LCS intake (median = 0, 11.3, and 124.2 mg/d for non-, lower, and higher consumers, respectively).</div></div><div><h3>Results</h3><div>Among the 572 study participants, the mean age was 52.5 y, 63.3% were female, 60.7% were on-Hispanic White, and 55.1% reported consuming LCS-containing products. Greater LCS consumption was not associated with anti-flagellin, anti-LPS, or total antibodies. Additionally, no associations between specific types of LCS and intestinal permeability biomarkers were observed.</div></div><div><h3>Conclusions</h3><div>The results of our study did not demonstrate an association between LCS consumption and intestinal permeability biomarkers. Further research with larger sample sizes and randomized controlled trials is needed to confirm our findings.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"155 4","pages":"Pages 1226-1235"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542387","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}
Sultan Mehmood Siddiqi , Lishun Liu , Yiming Du , Yun Song , Ping Chen , Shuqun Li , Qiangqiang He , Ziyi Zhou , Jiafeng Xu , Jie Bai , Binyan Wang , Xianhui Qin , Anam Mehmood , Liu Xiuqing , Xiaoxu Cheng , Han-Ping Shi
{"title":"Association of MTHFR C677T, MTHFRA1298C, and MTRRA66G Gene Polymorphisms with Hyperhomocysteinemia and Its Modulation by the Combined Effect of Vitamin B12 and Folate in Chinese Population with Hypertension","authors":"Sultan Mehmood Siddiqi , Lishun Liu , Yiming Du , Yun Song , Ping Chen , Shuqun Li , Qiangqiang He , Ziyi Zhou , Jiafeng Xu , Jie Bai , Binyan Wang , Xianhui Qin , Anam Mehmood , Liu Xiuqing , Xiaoxu Cheng , Han-Ping Shi","doi":"10.1016/j.tjnut.2024.09.003","DOIUrl":"10.1016/j.tjnut.2024.09.003","url":null,"abstract":"<div><h3>Background</h3><div>In China, the <em>MTHFR 677T</em> allele, unlike in most Western populations, is a rare genetic variant linked to various disorders. The contributing nutritional and genetic factors to this genetic risk remain unclear.</div></div><div><h3>Objective</h3><div>This study aimed to elucidate the interactions between genetic variations in total homocysteine (tHcy) pathway genes, serum tHcy concentrations, and nutritional factors in a Chinese population with hypertension.</div></div><div><h3>Methods</h3><div>This study analyzed 1304 Chinese adults with hypertension aged ≥18 y enrolled in the China Precision Nutrition and Health KAP Real World Study (CPNAS). Serum concentrations of vitamin B12 and folate were measured using the magnetic microparticle chemiluminescence method, and tHcy concentrations were measured using Hcy Assay kits. Identification of the <em>MTHFR C677T</em>, <em>MTHFR A1298C</em>, and <em>MTRR A66G</em> polymorphisms was performed via time-of-flight nucleic spectrometry.</div></div><div><h3>Results</h3><div>Our findings revealed significant sex differences in tHcy concentrations, with males exhibiting higher tHcy concentrations than females (13.95 μmol/L vs. 11.15 μmol/L, <em>P</em> < 0.001). Individuals deficient in both vitamin B12 and folate had an increased risk of hyperhomocysteinemia (H-Hcy) (57.4%). In contrast, the prevalence of H-Hcy was lower among those deficient in either vitamin B12 (31.1%) or folate (23.2%) alone. Significant associations were identified between the <em>MTHFR C677T</em> and <em>A1298C</em> polymorphisms and elevated serum tHcy concentrations, particularly in individuals homozygous for the T allele. Conversely, the <em>MTRR A66G</em> genotype did not show a significant correlation with tHcy concentrations. Optimal vitamin B12 concentrations significantly modulated the genotypic effect on tHcy concentrations, with individuals having adequate vitamin B12 and folate exhibiting low tHcy concentrations, even among high-risk genotypes (TT).</div></div><div><h3>Conclusions</h3><div>Adequate concentrations of folate and vitamin B12 significantly reduce serum tHcy concentrations and mitigate the genotypic impact on tHcy concentrations, highlighting the potential for targeted nutritional interventions to manage cardiovascular risks associated with H-Hcy.</div><div>This trial was registered at <span><span>clinicaltrials.gov</span><svg><path></path></svg></span> as ChiCTR2100051983.</div></div>","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":"155 4","pages":"Pages 1202-1209"},"PeriodicalIF":3.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289548","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}