Christian Zielinski, Victor Schmalle, Luise A. Lauer, Tim Hammerschick, Felix Rüttler, Walter Vetter, Jan Frank, Felipe Jiménez-Aspee
{"title":"Uptake and Transport of Monotropein and Monotropein Esters in a Caco-2/HT29-MTX-E12 Co-Culture Model","authors":"Christian Zielinski, Victor Schmalle, Luise A. Lauer, Tim Hammerschick, Felix Rüttler, Walter Vetter, Jan Frank, Felipe Jiménez-Aspee","doi":"10.1002/mnfr.70571","DOIUrl":"https://doi.org/10.1002/mnfr.70571","url":null,"abstract":"<p>Iridoids are dietary phytochemicals with diverse bioactivities, but their intestinal absorption remains poorly understood. We investigated the uptake, transepithelial transport, and early metabolism of monotropein and two esters (monotropein-10-coumarate and monotropein-10-cinnamate) using a validated Caco-2:HT29-MTX-E12 co-culture model. In silico analysis showed high polarity (>186 Å<sup>2</sup>) and predominant ionization at intestinal pH (p<i>K</i><sub>a</sub> ∼ 4.10–4.14), consistent with low passive permeability. Cellular uptake was rapid and largely time-independent. Monotropein uptake increased at 4°C versus 37°C, suggesting reduced efflux or metabolism rather than active transport; esters were unaffected. Transepithelial transport was low but increased at apical pH 6.0 compared to pH 7.4. Parallel artificial membrane assays (PAMPA) confirmed low passive permeability. Transporter inhibition indicated partial involvement of sodium–glucose cotransporter 1 (SGLT1) and organic anion transporting polypeptides (OATP) in monotropein uptake. Untargeted HPLC-MS detected no metabolites, and esters were not hydrolyzed. Overall, permeability was limited and not improved by esterification, suggesting low systemic exposure and a potential role for colonic and hepatic metabolism in vivo.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 15","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.70571","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148616740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thelma Rún Rúnarsdóttir, Sigurlaug Skírnisdóttir, Hildur Thors, Hjördís Harðardóttir, Karla F. Corral-Jara, Alexandra M. Klonowski, Þórhallur Ingi Halldórsson, Marta Guðjónsdóttir
{"title":"Effect of Chitosan Supplementation and Lifestyle Changes on Health and Gut Microbiota in Icelandic Females With Obesity","authors":"Thelma Rún Rúnarsdóttir, Sigurlaug Skírnisdóttir, Hildur Thors, Hjördís Harðardóttir, Karla F. Corral-Jara, Alexandra M. Klonowski, Þórhallur Ingi Halldórsson, Marta Guðjónsdóttir","doi":"10.1002/mnfr.70558","DOIUrl":"10.1002/mnfr.70558","url":null,"abstract":"<p>Evaluate the effect of chitosan supplementation with structured lifestyle changes on health factors and gut microbiota in females with obesity following an interdisciplinary rehabilitation program. In this randomized, double-blind, placebo-controlled trial (NCT04551365), 33 Icelandic females with obesity (BMI 30.0–54.1 kg/m<sup>2</sup>) received 3 g/day of LipoSan Ultra chitosan (TRG, <i>n</i> = 18) or placebo (PLG, <i>n</i> = 15) for 12 weeks, alongside structured lifestyle changes. Clinical, anthropometric (DXA), and functional data were collected at baseline (T1) and post-intervention (T3). Gut microbiota (16S rRNA) data were collected at T1, T2 (2 weeks), T3, and T4 (2 weeks post-intervention). Structured lifestyle interventions increased lean mass, grip strength, endurance, and self-rated health, while reducing body fat mass and mean arterial pressure across BMI groups. Participants with BMI ≥ 40 kg/m<sup>2</sup> showed decreased microbiota diversity over time. Chitosan supplementation was linked to a reduction in the <i>Firmicutes/Bacteroidota</i> ratio, although no differentially abundant taxa were identified (ANCOM-BC2). Structured lifestyle interventions improved body composition and physical function, independently of weight loss. Chitosan supplementation modulated gut microbiota composition. Interpretation of subgroup and gut microbiota findings is constrained by the study size. Future studies should investigate long-term effects and stratify outcomes by BMI to better evaluate chitosan's therapeutic potential.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 15","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mnfr.70558","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148596822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. V. Salini, Battula Narsimlu, Angela Joseph, Manorama Kumari, Pradip V. Behare
{"title":"Preclinical Safety and Toxicological Assessment of Vitamin B12 Producing Probiotic Limosilactobacillus reuteri NCDC 958","authors":"S. V. Salini, Battula Narsimlu, Angela Joseph, Manorama Kumari, Pradip V. Behare","doi":"10.1002/mnfr.70546","DOIUrl":"10.1002/mnfr.70546","url":null,"abstract":"<div>\u0000 \u0000 <p>The development of functional dairy foods using probiotic cultures with additional nutritional benefits has gained considerable attention. <i>Limosilactobacillus reuteri</i> NCDC 958 (LRN958) has been identified as a probiotic strain with the ability to produce vitamin B<sub>12</sub>; however, establishing its safety profile is essential for its successful application in food and human use. In this study, the preclinical safety of the vitamin B<sub>12</sub>-producing LRN958 strain was assessed using integrated in vitro and in vivo approaches. In vitro evaluation revealed that the strain lacked virulence-associated genes, did not produce biogenic amines or degrade mucin, and was susceptible to recommended antibiotics. In vivo safety was examined through acute, sub-acute, and sub-chronic oral toxicity studies in mice. Administration of LRN958 caused no mortality or clinical signs of toxicity. Body weight, hematological and biochemical parameters, organ indices, and histopathology remained comparable to controls. No bacterial translocation was observed, and immune markers, including IgA, IgG, IL-10, TGF-β, IL-6, and TNF-α, which showed no significant differences, indicating maintained immune homeostasis. The no-observed-effect level (NOEL) was 10<sup>10</sup> CFU/mouse/day. Overall, the findings confirm that LRN958 is safe, non-pathogenic, and supports its potential clinical use and application in probiotic and functional food formulations.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 15","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148596860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patrick Borel, Mark Pretzel Zumaraga, Charles Desmarchelier
{"title":"Genetic Determinants of Interindividual Differences in Provitamin A Carotenoid Concentrations in Human Adipose Tissue","authors":"Patrick Borel, Mark Pretzel Zumaraga, Charles Desmarchelier","doi":"10.1002/mnfr.70557","DOIUrl":"10.1002/mnfr.70557","url":null,"abstract":"<p>Adipose tissue is a major storage site for provitamin A carotenoids (proVA CAR)—mainly β-carotene (BCAR), α-carotene (ACAR), and β-cryptoxanthin (BCRY). However, the determinants of their concentrations in this tissue remain poorly understood. This study aimed to identify genetic variants associated with adipose tissue proVA CAR concentrations. Periumbilical adipose tissue samples were collected on six occasions in 43 healthy adult males and proVA CAR concentrations were quantified by HPLC. Participants were genotyped for 2,398 SNPs in 44 candidate genes involved in CAR and lipid metabolism, and genetic associations were assessed using partial least squares (PLS) regression. Adipose tissue proVA CAR concentrations ranked as BCAR > ACAR > BCRY, with CV ranging from 54 to 66%. PLS regression models integrating fasting plasma proVA CAR concentrations and SNPs explained 69, 59, and 67% of the variability in BCAR, ACAR, and BCRY concentrations, respectively. In a multivariate PLS regression model, the main determinants of proVA CAR concentrations were fasting plasma BCAR and ACAR concentrations and four SNPs—rs4694627 (<i>CXCL8</i>), rs7558381 (<i>IRS1</i>), rs709157 and rs1152004 (<i>PPARG</i>). Interindividual variability in adipose tissue proVA CAR concentrations is partly explained by genetic variation in genes involved in CAR and lipid metabolism.</p><p><b>Clinical Trial Registry</b>: ClinicalTrials.gov registration number NCT02100774.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 14","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faizah Fulyani, Iftitan Setya Widayanti, Salwa Alifa Bestari, Lusiana Batubara, R.R. Mahayu Dewi Ariani, Charlie Roosevelt D.H., Muhammad Ichsanul Fikri, Galen Chandrawira, Rio Jati Kusuma
{"title":"Intermittent Fasting Amplifies Gut–Endocrine Axis Responses to Senna alexandrina Supplementation in Obese Rats","authors":"Faizah Fulyani, Iftitan Setya Widayanti, Salwa Alifa Bestari, Lusiana Batubara, R.R. Mahayu Dewi Ariani, Charlie Roosevelt D.H., Muhammad Ichsanul Fikri, Galen Chandrawira, Rio Jati Kusuma","doi":"10.1002/mnfr.70531","DOIUrl":"10.1002/mnfr.70531","url":null,"abstract":"<div>\u0000 \u0000 <p>Obesity induced by high‑fat, high‑sucrose diets (HFSD) remains a major global health challenge, disrupting lipid metabolism, glucose homeostasis, and gut microbial balance. These disturbances underscore the need for safe interventions capable of restoring metabolic regulation. <i>Senna alexandrina</i> (SA), traditionally used for weight reduction, has recently been shown to modulate the gut microbiota beyond its laxative effects. To enhance efficacy while minimizing adverse outcomes, this study investigated the effects of a low and safe dose of SA combined with intermittent fasting (IF), a strategy that reshapes nutrient availability and microbial dynamics. HFSD‑induced obese rats were treated for four weeks with SA leaf powder (300 mg/kg/day), IF, or both. Bioactive constituents of SA were characterized using LC‑HRMS, alongside systematic evaluation of physiological and metabolic parameters—including adiposity, morphometry, lipid profiles, insulin sensitivity markers, and gut-endocrine axis indicators. SA supplementation showed improvements across all parameters, surpassing those achieved with IF alone. Importantly, the combined intervention (SA+IF) yielded complementary benefits, notably enhancing GLUT4 expression, short‑chain fatty acid (SCFA) production, peptide YY (PYY) secretion, and reducing the Firmicutes/Bacteroidetes ratio. These findings highlight the complementary roles of SA and IF in metabolic regulation, providing experimental evidence for a potential dietary approach to mitigate obesity‑related dysfunction.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 14","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hang Gao, Yu Sheng, Yang Ge, Feng-Yuan Chen, Zheng-Rong Zhang, Jun Chu, Hang Song
{"title":"Therapeutic Potential of Polysaccharide-Modulated Gut Microbiota–Immune Axis in Gastrointestinal Cancers: Modern Insights From Traditional Pharmacy","authors":"Hang Gao, Yu Sheng, Yang Ge, Feng-Yuan Chen, Zheng-Rong Zhang, Jun Chu, Hang Song","doi":"10.1002/mnfr.70561","DOIUrl":"10.1002/mnfr.70561","url":null,"abstract":"<div>\u0000 \u0000 <p>Gastrointestinal (GI) cancers are a leading cause of cancer-related death worldwide, while drug resistance and treatment-related toxicity continue to limit therapeutic efficacy. A growing body of evidence indicates that the gut microbiota-immune axis (GMIA) is closely involved in the development, progression, and treatment response of GI malignancies. In this review, we summarize current understanding of how gut microbial dysbiosis and GMIA dysfunction contribute to GI cancer development and progression. We highlight the role of natural polysaccharides in modulating gut microbial composition and microbial metabolites, thereby influencing host immune responses and exerting antitumor potential in preclinical settings. In addition, we review recent advances in representative natural polysaccharides as promising candidates for the prevention and treatment of gastrointestinal cancers, with an emphasis on their translational prospects and priorities for future investigation.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 14","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wenyu Yang, Qiqi Li, Tong Tong, Wenhui Ye, Wei Wei
{"title":"Chronic Aspartame Exposure Leading to Hypertension in Mice may be Related to the Activation of the Wnt/β-Catenin Signaling Pathway in the Hypothalamus","authors":"Wenyu Yang, Qiqi Li, Tong Tong, Wenhui Ye, Wei Wei","doi":"10.1002/mnfr.70563","DOIUrl":"10.1002/mnfr.70563","url":null,"abstract":"<div>\u0000 \u0000 <p>Aspartame is a commonly used sweetener that is increasingly becoming the main source of sweetness in foods due to its low-calorie and high-sweetness characteristics. Excessive intake of aspartame can lead to the occurrence of cardiovascular metabolic diseases and metabolic syndrome, especially hypertension. However, research on the correlation between exposure to aspartame and the development of hypertension remains insufficient. The hypothalamus is the main site regulating blood pressure. Our study established a chronic aspartame exposure model by administering 50 mg/kg aspartame water, measured the blood pressure of 4-week-old mice, and analyzed hypothalamic transcriptomic changes through full-length transcriptome sequencing. The results showed that chronic aspartame exposure significantly increased blood pressure in mice (<i>p</i> < 0.05). Full-length transcriptome sequencing identified 630 differentially expressed transcripts between the control and aspartame groups, with enrichment analysis showing significant changes in terms and pathways related to nervous system development and blood pressure. In addition, we found that increased neuronal necrosis in the paraventricular nucleus of the hypothalamus, and the Wnt/β-catenin signaling pathway was significantly activated in the aspartame group. In summary, our study suggested that chronic aspartame exposure is associated with elevated blood pressure in mice and affects the development of the hypothalamus at the transcript level.</p>\u0000 </div>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 14","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lara Huber, Eduard Flores Ventura, Regina Ensenauer, Daria Guseva
{"title":"Human Milk Bioactive Compounds and Psychomotor Outcomes in Infants and Children: A Systematic Review","authors":"Lara Huber, Eduard Flores Ventura, Regina Ensenauer, Daria Guseva","doi":"10.1002/mnfr.70553","DOIUrl":"10.1002/mnfr.70553","url":null,"abstract":"<p>Human milk (HM) provides nutrients and bioactive compounds (BCs) essential for healthy child development. This systematic review aimed to evaluate the short- and long-term effects of individual groups of BCs on psychomotor outcomes, including motor, cognitive, language, and executive functions. A comprehensive literature search was conducted in MEDLINE (PubMed), Scopus, Web of Science, and Embase in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligibility was defined using the PECOTS framework, focusing on healthy, term, breastfed children with follow-up up to 18 years. Study quality was assessed with the Joanna Briggs Institute (JBI) tool and Cochrane Risk of Bias (RoB 2) tools. Eighteen studies met the inclusion criteria. The most consistent evidence was for polyunsaturated fatty acids (PUFAs), particularly n-3 PUFAs, which were generally associated with favorable psychomotor outcomes throughout infancy and later childhood. In contrast, higher levels of n-6 PUFAs showed less consistent or potentially unfavorable associations. Among HM oligosaccharides, fucosylated HMOs were consistently associated with improved cognitive and language-related outcomes, whereas evidence for other HMO groups was limited and heterogeneous. Findings related to proteins, phospholipids, sphingolipids, and carotenoids were inconsistent. HM BCs, particularly n-3 PUFAs and fucosylated HMOs, may support psychomotor development in infancy, preschool age, and school age. However, the overall evidence remains heterogeneous. Further research using standardized methodologies is required to elucidate long-term effects and underlying mechanisms.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 14","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Postbiotics: An Overview and Recommendations for Improved Reporting","authors":"Mehreen Anjum, Arthur C. Ouwehand","doi":"10.1002/mnfr.70554","DOIUrl":"10.1002/mnfr.70554","url":null,"abstract":"<p>Postbiotics, a term gaining traction among scientists and consumers, refers to nonviable microbial products or components that confer health benefits to the host. Despite their growing recognition, there is no generally accepted definition, with various interpretations and historically used terms around their physical nature, including intact dead cells, lysates, and intra- and extracellular metabolites. We review postbiotic research reporting practices, with special focus on clinical studies. Postbiotics demonstrate superior stability, extended shelf life, and broader applicability compared to probiotics. Nevertheless, they are susceptible to oxidative or enzymatic degradation, can be potentially allergenic, and may harbor DNA with transferable antibiotic resistance genes. We identified 101 clinical studies on postbiotics. Not included in this are studies on yeast β-glucan (estimated at least 34 studies). Most studies reported on the use of products obtained from single strains, only 12 studies investigated mixed-strain preparations and heat-treated yogurt. For inactivation, heat-treatment was reported by 69 studies. There was substantial variation in temperatures: 70–140°C, and duration: 4s to 10 h. Postbiotic study reporting is diverse and should improve. We suggest the following recommendations: reporting proper taxonomy of source organism, using proper terminology of inactivation method and provide method details, report administered quantity, provide information on quality control.</p>","PeriodicalId":212,"journal":{"name":"Molecular Nutrition & Food Research","volume":"70 14","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13392594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}