Frontiers in Nutrition

Background & aims: The human gut microbiota plays a key role in health. Factors shaping its composition and diversity have been widely studied during infancy and adulthood, but far less in adolescence, despite this being a key developmental stage. We examined the potential associations between the gut microbiota of adolescents and 82 variables measured from pregnancy to adolescence. Methods: Stool samples were collected from 366 adolescents (age range: 13-16 years) from two INMA cohorts (Spain), while a range of variables, including diet, lifestyle, sociodemographic factors, health status, antibiotic use, vaccination, COVID-19, anthropometrics, and pubertal development, were collected from pregnancy to adolescence. The gut microbiota was characterized using 16S rRNA gene sequencing and assessed using - and {beta}-diversity indices and individual taxa. Associations with the study variables were evaluated using linear models, permutational multivariate analysis of variance (PERMANOVA), and Microbiome Multivariable Association with Linear Models (MaAsLin2). Results: During pregnancy, vegetable intake was positively associated with -diversity and with both {beta}-diversity and the abundance of four genera (three inverse associations and one positive association). Legume intake was also inversely associated with two genera. During adolescence, cereal and pasta intake was positively associated with -diversity and {beta}-diversity, and was inversely associated with Bacteroides, whereas fish and seafood intake was inversely associated with -diversity. Other relevant variables measured during pregnancy and at birth, such as biological sex, parental social class, and maternal education, and during adolescence, such as antibiotic use, body mass index, and pubertal status, were also associated with {beta}-diversity indices and different taxa in both directions. Conclusions: Diet during pregnancy and adolescence, together with some anthropometric, clinical, and biological factors, appeared to play an important role in shaping the composition and diversity of the gut microbiota in this population of adolescents.

Importance: Food and non-alcoholic beverage marketing drives children's dietary intake, yet updated evidence quantifying effects by marketing medium and sociodemographic factors is needed to inform policy. Objective: To quantify the effect of food marketing on dietary intake among children and adolescents (0-19 years) and examine variations by age, sex, socioeconomic position (SEP), weight status, marketing medium, and exposure duration. Data Sources: Nineteen electronic databases were searched for articles published from April 2020 to February 2026, complemented by World Health Organization-commissioned reviews covering 1970 to March 2020. Study Selection: Two reviewers independently selected peer-reviewed primary studies that assessed the association between food marketing and dietary intake, following PRISMA guidelines, with no language restrictions. Data Extraction and Synthesis: Two reviewers independently extracted data and assessed the risk of bias. Random-effects meta-analyses were conducted. The certainty of evidence was assessed using GRADE. Main Outcomes and Measures: Dietary intake (energy, quantity, or number of items consumed). Results: A total of 55 studies (N = 6,877; range 2-18 years) were included. Food marketing was associated with higher dietary intake (mean difference [MD], 34.8 kcal; 95% CI, 20.2-49.4) compared with no or less marketing. Unhealthy marketing via television (20 studies; MD, 44.5 kcal; 95% CI, 11.2-77.8), digital media (11 studies; MD, 37.5 kcal; 95% CI, 20.1-54.9), and packaging (11 studies; MD, 20.5 kcal; 95% CI, 0.7-40.3) all increased intake; the difference across media was significant (p < .001). Higher intake was observed in males (3 studies; MD, 51.9 kcal; 95% CI, 45.4-58.3) but not in females (MD, -6.8 kcal; 95% CI, -60.3-46.6); difference was not significant (p = .082). Differences by weight status (p = .012) were seen (5 studies; normal weight: MD, 55.6 kcal; 95% CI, -51.3-162.5; overweight/obese: 146.9 kcal; 95% CI, 34.1-259.7). Effects varied by age (p = .003) and by digital media exposure duration (p = .044). One study examined ethnicity; none studied SEP. Conclusions and Relevance: Food marketing is associated with increased dietary intake, with low certainty of evidence. Variations were observed across age, sex, weight status, and marketing medium. Further research is needed for adolescents and the role of SEP.

BackgroundDespite the advancements in infant nutrition, a gap still exists in the nutritional composition bioactive ingredients between infant formula and human milk. We developed a next-generation, proof-of-concept infant formula that contains recombinant human milk proteins. ObjectiveTo determine the impact of a novel infant formula (H1) on organ growth and development, and intestinal function compared to donor human milk (DHM) and standard infant formula (S) in a term piglet model. MethodsTerm piglets delivered via cesarean section were fed either a donor human milk (DHM) control, the investigational formula (H1), or infant formula (S) for 10 days. On d 10, a blood sample and tissues were collected. ResultsThere was no difference (P > 0.05) in piglet growth, although H1 piglets had a smaller relative stomach and liver than DHM and S piglets. H1 piglets had higher (P < 0.05) interleukins in the distal ileum, but no other systemic cytokines were elevated compared to the DHM and S piglets. H1 piglet small intestinal histology was similar (P > 0.05) to that of DHM and S piglets. Additionally, H1 piglets had either the same (P > 0.05) or higher (P < 0.05) amino acids in circulation compared to DHM and S piglets. Recombinant human proteins had either similar (P > 0.05) or lower (P < 0.05) activity compared to the native human proteins when assessing the individual ingredients in the H1 formula. ConclusionH1 formula was noninferior to DHM and S based on growth, small intestinal histology and plasma amino acid endpoints when fed to neonatal piglets. These findings warrant further studies to use the neonatal piglet as a model to evaluate more in-depth outcomes of health and safety for new infant formulas. Lay SummaryA novel piglet study shows a hypoallergenic, next-generation infant formula containing recombinant human milk proteins rivals donor human milk and standard formula for growth, gut health, and nutrient status.

Despite known carcinogenic properties, indoor tanning remains popular among young adults and may contribute to early-onset melanoma. Our study aims to compare early-onset melanoma incidence by state availability of tanning beds. We analyzed population-based melanoma incidence data (2019-2023) from the National Program of Cancer Registries and calculated Incidence Rate Ratios (IRR) using verified state-level quintiles of tanning bed availability. Overall, in the Midwest/South regions, melanoma incidence increased with greater tanning-bed availability, from 8.7 cases per 100,000 population in Quintile 1 to 14.8 cases per 100,000 population in Quintile 5 (IRR = 1.69; CI = 1.65-1.74). No such relationship was found in the Northeast/West regions. In conclusion, we found that in Southern and Midwest states, increased availability of tanning beds was associated with higher early-onset melanoma in non-Hispanic White males and females, in both metro and non-metro counties. Policies which reduce tanning bed availability in high utilization regions may have potential to reduce early-onset melanoma.

Purpose: Iron deficiency impairs sports performance, and female athletes are particularly vulnerable. High-dose iron supplements, commonly used to prevent iron depletion and performance impairments, may cause gastrointestinal side effects and disrupt the gut microbiota. Whether lower doses can improve iron status without adverse effects remains unclear. The aim of this study was to characterize iron intake and iron status in female soccer players during the competitive season and investigate effects of low-dose iron supplementation on iron status, safety-related outcomes and gut microbiota. Methods: In a two-arm parallel randomized controlled trial, female soccer players (median age 21) were randomized to an intervention group (n=12) receiving 3-month low-dose iron supplementation (27 mg elemental iron/day) or a control group (n=11) without supplementation. Blood/fecal samples were collected at baseline and 3-month follow-up. Dietary intake was estimated using 7-day food diaries. Between-group differences were analyzed per protocol (n=18) using ANCOVA with baseline adjustment. Results: The players had inadequate baseline iron intake (median 11.2 mg/day) and 43% had serum ferritin indicating iron depletion (<35 g/L). At follow-up, no significant between-group difference was found for serum ferritin, but fewer athletes in the intervention group experienced decreases from baseline to follow-up (P<0.05). Moreover, serum iron was higher in the intervention group (Pgroup=0.05). No between-group differences were observed for gastrointestinal symptoms or liver damage biomarkers. On the contrary, the intervention led to lower IL-6 (Pgroup=0.04) and higher gut microbial -diversity (Pgroup=0.01) compared to controls. Conclusions: The low-dose iron supplementation was well tolerated, attenuated decreases in iron stores, increased gut microbial diversity and attenuated systemic inflammation in female soccer players with suboptimal dietary iron intake. However, potential adverse effects of long-term exposure cannot be excluded.

Micronutrient deficiencies are prevalent in Madagascar, where diets rely heavily on starchy staples and access to animal-source foods is limited. Small dried fish (SDF) are widely available, yet their nutritional value and health risks remain poorly documented. We combined market surveys, taxonomic identification, and micronutrient and heavy metal analyses of nine SDF types collected along National Road 7. The samples encompassed 33 fish families, were dominated by small pelagic species (Clupeidae and Engraulidae), and were appreciated by consumers. A daily portion (5 g for infants; 10 g for young children and women of childbearing age) contributed substantially to Recommended Nutrient Intakes (RNIs). Across samples and groups, SDF were rich (>30% of RNI) in selenium and, for infants and young children, in calcium. All samples were a source of (>15% of RNI), or rich in, phosphorus, whereas iron contributions were more variable but often substantial. Several samples exceeded 100% of RNIs for selenium, calcium, iron, or manganese in infants and young children, and some were also sources of magnesium and, less frequently, zinc. Vitamin A was absent from sun-dried samples but detected in a smoked freshwater type. Heavy metal concentrations varied markedly, and portions of several types led to estimated exposures to inorganic arsenic or cadmium exceeding reference values, whereas freshwater species and some pelagic types showed a more favorable nutrition-risk balance. Overall, SDF are affordable, nutrient-dense foods with strong potential to alleviate micronutrient deficiencies in Madagascar, while highlighting the need for type-specific guidance to balance nutritional benefits and contamination risks.

Dairy-free foods must reproduce diverse functions of dairy, from foam stabilization in a latte to acid-gel structure in yogurt and melt-stretch behavior in mozzarella. Public consumer benchmarks rarely compare these categories under a common protocol. Here we analyze data from the NECTAR Taste of the Industry 2026 study, a blinded, randomized, in-person evaluation of commercial dairy-free products and dairy benchmarks. The full study included 2,183 consumers and 112 products across ten categories, with 3,220 product evaluations and 79,027 recorded survey responses, including 35,762 product-linked responses. The ten categories included barista milk, butter, cheddar, cream cheese, creamer, ice cream, fluid milk, mozzarella, sour cream, and Greek style yogurt. Within each category, we compare a dairy benchmark with the dairy-free product selected post hoc as the category leader. Participants rated overall liking, flavor, texture and mouthfeel, appearance, similarity to dairy, and purchase intent on seven-point scales and completed check-all-that-apply questions. In exploratory category-specific equivalence tests using a chosen margin of {+/-}0.05 points, barista milk, creamer, and fluid milk meet this margin. Mozzarella has the largest paired deficit of -1.46 points (unadjusted, p < 0.001), followed by Greek style yogurt and butter; all three remain significant after Holm correction across the ten primary comparisons. Descriptive penalty analysis associates off-flavor, artificial or chemical notes, stale or cardboard notes, bitter taste, and lingering aftertaste with the largest reductions in liking. Together, these results establish the first open sensory benchmark for dairy and dairy-free products, demonstrate that sensory parity is already achievable in several beverage categories, and identify the product categories and sensory attributes that offer the greatest opportunities for future innovation.

Background Childhood asthma has been linked to individual foods, nutrients, diet-quality scores, and broad dietary patterns, but specific early-childhood food co-consumption patterns and their microbial/metabolic correlates remain unclear. Objective To identify data-driven early-childhood dietary patterns associated with asthma/wheeze, evaluate prospective associations with age-6 asthma/wheeze, assess external support in NHANES, and characterize associated gut microbiome and stool/plasma metabolomic profiles. Methods We analyzed age-3 food frequency questionnaire data from children in the Vitamin D Antenatal Asthma Reduction Trial. Dietary patterns were derived from log-transformed, energy-residualized, standardized food-frequency variables using principal component analysis. Associations with age-3 asthma/wheeze were tested using covariate-adjusted logistic regression. Prospective associations were evaluated using age-6 asthma/wheeze as the outcome. Leading PC food-cluster proxies were evaluated in NHANES 2021-2023 among children aged 2-3 years, with sensitivity analyses in ages 2-5 and 2-8 years. Selected PCs were tested for associations with gut microbiome, stool metabolome, and plasma metabolome features. Results PC1 contrasted a sweet snack/fried-food pattern with a fruit/vegetable-rich pattern, whereas PC3 captured a processed meat/fried-food axis. PC3 showed the strongest positive association with age-3 asthma/wheeze (odds ratio per 1-SD increase, 1.42; P = 0.00109). Age-3 dietary PCs were prospectively associated with age-6 asthma/wheeze, with the overall PC set improving model fit in permutation testing (likelihood-ratio statistic = 20.3; empirical P = 0.033) among 394 cases and 397 controls. In NHANES children aged 2-3 years, the PC3 food-cluster proxy was positively associated with current asthma (odds ratio, 1.59; 95% confidence interval, 0.95-2.67). PC3 was also linked to gut microbial and stool/plasma metabolomic variation, including steroid sulfate, vitamin E-related, nucleoside-related, and lipid-related metabolites. Conclusions Early-childhood asthma/wheeze-associated dietary signals were better represented as food co-consumption patterns than isolated single-food effects. Age-3 dietary patterns were associated with concurrent and prospective asthma/wheeze, showed directionally consistent NHANES support, and were linked to microbiome and metabolomic variation.

Kakadu plum (Terminalia ferdinandiana), an Australian native fruit, is among the richest known dietary sources of vitamin C and hydrolysable tannins, yet its capacity to protect the intestinal epithelium against oxidative stress remains largely unexplored. This study optimised the extraction of bioactive compounds from freeze-dried Kakadu plum powder and evaluated their antioxidant activity using both chemical and cellular antioxidant in vitro assay. Phenolic compounds were extracted using three solvents (water, 80% ethanol, and 80% methanol) combined with shaking, ultrasound, or microwave assistance. Solvent, rather than processing technique, was the dominant determinant of antioxidant capacity: ethanol and methanol maximised total phenolic content, total flavonoid content, and DPPH radical-scavenging activity, whereas water extracts showed the highest ferric-reducing antioxidant power. Twenty-four phenolic compounds identified by HPLC-ESI-QTOF-MS/MS were mapped by network pharmacology to nine core oxidative-stress targets, and cross-species molecular docking predicted conserved binding of key phenolics to canine orthologs of PTGS2 and MMP2. In an H2O2-induced oxidative-stress in vitro cell model using canine small intestinal epithelial cells, both water (less than 25 ug/mL) and ethanol (less than 250 ug/mL) extracts significantly suppressed intracellular reactive oxygen species (ROS) in a dose-dependent manner, with the ethanol extract effective across a wider concentration range. This work demonstrated that Kakadu plum extract could be a promising natural, multi-target antioxidant ingredient for canine intestinal health, and provided a reference for future in vivo research.

Background: Early trophic feeding promotes gut maturation, feeding tolerance, and growth in preterm neonates. However, delays remain common despite recommendations for initiation within 24 hours of birth, especially in resource-limited settings. Evidence on feeding initiation timing and predictors among Ethiopian preterm neonates is limited. Objective: To determine time to trophic feeding initiation and identify predictors among preterm neonates admitted to Adama Hospital Medical College, Ethiopia. Methods: A hospital-based retrospective cohort study was performed on 436 randomly chosen preterm neonates admitted to NICU. Data extraction was performed using a structured checklist. Time to trophic feeding initiation was analyzed using Kaplan-Meier estimates, log-rank tests, and bivariable and multivariable Cox regression models . Adjusted hazard ratios with 95% CIs were reported. Results:The sample comprised 416 preterm neonates, of whom 311 (74.8%) started trophic feeding during follow-up, and 105 (25.2%) were censored. The rate of initiation of trophic feeding was 1.92 per 100 person-hours (95% CI 1.72 to 2.15). Median time to initiation was 42 hours (interquartile range 24 to 50). Independent predictors of feeding initiation were determined by multivariable analysis and included gestational age, birth weight, maternal anaemia, respiratory distress syndrome and necrotising enterocolitis. Neonates born at 34-36 weeks had earlier initiation than those born at <34 weeks (AHR 1.39; 95 % CI 1.09 to 1.78). Similarly, neonates with a birth weight of [&ge;]1500 g had an earlier initiation than those with a birth weight of <1500 g (AHR 1.41; 95% CI 1.04 to 1.91). Delayed initiation was associated with maternal anaemia (AHR 0.70; 95% CI 0.51-0.95), respiratory distress syndrome (AHR 0.67; 95% CI 0.51-0.88) and necrotising enterocolitis (AHR 0.48; 95% CI 0.33-0.69). Conclusions: Delayed trophic feeding remains common among preterm neonates. Standardized feeding protocols, strengthened maternal care, and individualized nutrition strategies are needed to improve neonatal outcomes in study area.

Background: Many epidemiological studies rely on dietary exposures taken from baseline only. This limits our understanding of diet-disease associations because it requires assuming a level of temporal stability, either by individuals or dietary pattern composition. Objectives: This study aimed to evaluate these analytic assumptions of pattern structure consistency and baseline adherence using a cohort of US Black women with repeated measures of food frequency questionnaires (FFQ). Methods: Data from 6151 Black women aged 21-69 from the Black Women's Health Study with complete FFQ data in 1995, 2001, 2013, and 2021 were evaluated for temporal stability. Baseline dietary patterns were derived using an overfitted latent class model. Parameter estimates from the baseline model were then applied to subsequent waves to track individual transitions between existing patterns. Dietary patterns were also derived at each time point using an overfitted latent class model and assessed for changes in pattern composition over time. Results: Five baseline dietary patterns were identified in 1995. Only 18% of participants remained in the same baseline dietary pattern across all four time points, while all others transitioned to a different baseline-derived pattern. Dietary patterns derived independently at subsequent time points, yielded a different number of dietary patterns at each time point (2001: 6 patterns, 2013: 5 patterns, 2021: 4 patterns). Correlation strength of subsequent derived patterns and baseline patterns significantly weakened in strength after 2001 (40% pairings > 0.5), with no patterns correlated greater than 0.5 in 2021. Conclusion: Prospective studies that rely on baseline dietary exposure data cannot assume stability of pattern composition or individual pattern adherence over time, as it ignores changes in dietary habits and may bias our understanding of the diet-disease pathway.

Abstract Background The gut microbiome has been widely studied in the context of obesity, and yet the reported associations vary widely across populations and analytical approaches. In Asian populations where the prevalence of obesity is rapidly rising, the extent to which gut microbiome features could associate with adiposity in a robust and generalizable manner remains unclear. Methods Population-scale shotgun metagenomic data was generated for adults (n=871) from the Health for Life in Singapore (HELIOS) cohort, comprising ethnic Chinese, Malay, and Indian participants. Integrated taxonomic, functional, and machine-learning-based analyses were used to assess associations between gut microbiome features and obesity, adjusting for demographic covariates and evaluating for robustness across multiple statistical frameworks. Results Global microbiome structure exhibited weak separation by body mass index (BMI), with enterotype-like clustering providing limited discriminatory power for obesity status. Differential abundance analyses identified a small number of method-dependent taxa and pathways, with only limited recurrence across methods. Supervised machine learning models trained on taxonomic profiles achieved modest predictive performance, particularly for intermediate BMI classes, and did not reveal robust microbial signatures beyond those detected by univariate analyses. Conclusions Our study highlights the importance of large-scale, multi-framework analyses for distinguishing robust microbiome-phenotype associations from weak, method-dependent signals. Together, our findings emphasize that obesity-associated microbiome signatures may be too weak, diffuse, and insufficient to explain adiposity in Asian populations.

Abstract Aim: Examine cross-sectional associations between mid-pregnancy food intake indicators and prenatal depressive symptomatology. Methods: This secondary analysis of the Comparison of Two Screening Strategies for Gestational Diabetes trial (N = 718) examined domains of mid-pregnancy food intake (direct timing, energy timing, meal/snack structure, meal energy distribution, diet quality) derived from 24-hour dietary recalls. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS). Generalized linear models examined associations between food intake indicators, total, and high (EPDS [&ge;]13) depressive symptoms. Results: Mean (SD) EPDS score was [6.3 (4.9)]; 12.4% (n = 89) had high depressive symptoms. Eating frequency (B = 0.08 [0.02, 0.14], p = 0.009), snack frequency (B = 0.06 [0.00, 0.12], p = 0.040), nighttime snacking frequency (B = 0.06 [0.00, 0.11], p = 0.041), and total daily energy intake (B = 0.06 [0.01, 0.12], p = 0.031) were positively associated with total depressive symptoms. Energy intake from breakfast (PR = 1.2 [1.0, 1.3], p = 0.017) was associated with a higher prevalence of high depressive symptoms. Energy intake from dinner (PR = 0.81 [0.69, 0.94], p = 0.007), later timing of the first eating episode (PR = 0.83 [0.70, 0.99], p = 0.034) and first energy quartile (PR = 0.84 [0.70, 1.0], p = 0.048), were associated with a lower prevalence of high depressive symptoms. Conclusion: These findings extend prior chrononutrition-depression literature to the prenatal period, implicating eating frequency, energy intake, and meal energy timing and distribution in depressive symptomatology during pregnancy, warranting further longitudinal investigation.

Early-life microbiota represent an indispensable factor for the proper development and function of host metabolism and the immune system. We have demonstrated that neonatal exposure to antibiotics for the first 3 weeks (NeoATB) leads to obesity in adulthood, characterized by gut microbiota dysbiosis and dysregulated immune responses. Here, we demonstrate that feeding D-mannose suppresses NeoATB-induced obesity, accompanied by improved glucose tolerance and decreased insulin resistance. Mechanistically, D-mannose feeding decreased hypoxia and increased oxygenation and recovery of metabolic activity of adipocytes. D-mannose restored CD4+Foxp3+ST2+ Tregs, leading to a reduction of Th1 pro-inflammatory cells in the adipose tissue of NeoATB mice. Significantly, we revealed that D-mannose treatment reversed the dysregulated ratios of phylum Firmicutes to phylum Bacteroidetes in obese NeoATB mice, which was surprisingly attributed to D-mannose-mediated suppression of the growth of Firmicutes rather than an increase in the growth of Bacteroidetes. These findings should have therapeutic implications for the treatment of obesity in human patients.

Plant-based diets may benefit planetary and human health. However, the molecular pathways linking plant-based diet quality to chronic diseases remain unclear. In 4,372 participants from the European Prospective Investigation into Cancer and Nutrition, we assessed 7,285 SomaScan-measured aptamers to identify circulating proteins associated with healthful (hPDI) and unhealthful (uPDI) plant-based dietary patterns using complementary statistical and machine-learning approaches. We then applied cis-pQTL Mendelian randomization (MR) and colocalization to prioritize diet-associated proteins with genetic evidence for associations with overall and site-specific cancers, type 2 diabetes (T2D), and cardiovascular disease (CVD). Among diet-associated proteins with MR evidence, 8 hPDI- and 12 uPDI-related protein-disease associations showed strong colocalization, including EGFR-breast cancer, MMP10-endometrial cancer, NCAN-T2D, and PCSK9-CVD. These findings identify candidate proteins that may link plant-based diet quality to chronic diseases and provide biological insights into the potential health benefits of healthful plant-based diets, which are increasingly relevant to public and planetary health.

Inflammatory bowel disease (IBD) is associated with chronic intestinal inflammation and gut microbial dysbiosis, yet effective microbiome-targeted therapeutics remain limited. Here, we investigated the anti-inflammatory and microbiome-modulating activities of metabolites isolated from Garcinia brassii, an endemic species of the Australian Wet Tropics. Five compounds, including a new natural product named garcitine, were isolated and structurally characterised. In human immune cells, garcinol and garcinia biflavonoid 1 significantly suppressed lipopolysaccharide-induced production of IL-1{beta}, IL-6, and TNF without detectable cytotoxicity, while parvifoliol F selectively inhibited IL-1{beta} release. Therapeutic efficacy was further evaluated in a TNBS-induced murine colitis model, where garcinia biflavonoid 1 and parvifoliol F significantly reduced colonic inflammation and improved histopathological outcomes. 16S rRNA sequencing demonstrated that both compounds restored gut microbial homeostasis by reversing colitis-associated dysbiosis and reducing inflammation-associated microbial signatures. Functional pathway prediction further suggested suppression of pro-inflammatory microbial metabolic pathways following treatment. Together, these findings demonstrate that Garcinia-derived metabolites alleviate experimental colitis through coordinated immunomodulatory and microbiome-reprogramming mechanisms and identify garcinia biflavonoid 1 and parvifoliol F as promising candidates for microbiome-targeted IBD therapeutics.

The analysis uses a global 2010-2023 panel comprising 3,038 economy-years across 217 economies. It explicitly separates between-economy and within-economy estimands and tests the longitudinal interpretation using an identical-sample temporal analysis with cluster-aware coefficient contrasts, a formal isometric log-ratio sensitivity analysis, independent fixed-effects replication, and wild-cluster-bootstrap inference. The central finding is deliberately calibrated: cross-economy agreement cannot validate national sugar availability for longitudinal obesity surveillance. The study identifies temporal and construct instability without claiming that sugar is protective or that the mechanisms producing the instability have been identified. The manuscript aligns well with PLOS ONEs emphasis on technically sound, transparent and reproducible research of broad relevance. All data required to reproduce the findings, complete metadata, executable code, full-precision results, diagnostic outputs and a completed STROBE checklist are provided as S1-S5. Figures are provided separately as compliant 350-dpi TIFF files. The study used only publicly available, aggregated economy-year statistics and involved no individual participants, identifiable information or biological specimens; institutional ethics review and consent were therefore not required. This is original work; it is not under consideration elsewhere, and the sole author has approved the submission and accepts responsibility for its content. Funding and competing-interest declarations will be entered accurately in the submission portal. An Academic Editor with expertise in nutritional epidemiology, global health metrics, longitudinal panel methods, or food-system surveillance would be well placed to assess the work.

Background: The growing burden of lifestyle-related chronic diseases has increased the need for clinically interpretable decision-support tools capable of integrating artificial intelligence with evidence-based preventive nutrition. Although machine learning has shown considerable potential for health risk prediction, most existing approaches remain limited to isolated predictive models or conventional nutritional software, with little integration of multidimensional clinical assessment and personalized recommendations. Objective: To develop and internally validate NutrIA, a hybrid web-based Clinical Decision Support System (CDSS) that combines machine learning, validated clinical assessment, structured clinical reasoning and personalized nutritional recommendations for preventive medicine. Methods: NutrIA was developed using harmonized data from the National Health and Nutrition Examination Survey (NHANES, 1988 to 2018). A supervised machine learning model was trained to estimate 5-, 10- and 20-year all-cause mortality risk and subsequently integrated with an adaptive clinical questionnaire, validated screening instruments, nutritional indicators, dietary clustering, clinical phenotyping and a transparent rule-based recommendation engine within a unified web-based platform. Results: The predictive model achieved ROC-AUC values of 0.894, 0.914 and 0.923 for 5-, 10- and 20-year mortality prediction, respectively. The implemented CDSS incorporates an adaptive questionnaire (151 items), 39 validated clinical assessment instruments, 17 clinical phenotypes and 31 dietary clustering modules to generate individualized nutritional and lifestyle recommendations together with an automated clinical report. The integrated framework translates probabilistic risk estimates into clinically interpretable decision support for personalized preventive nutrition. Conclusions: NutrIA demonstrates the technical feasibility of integrating machine learning with knowledge-based clinical reasoning within a single web-based CDSS for preventive nutrition. Although external validation and prospective clinical evaluation are required before routine implementation, the proposed architecture represents a promising step toward clinically interpretable artificial intelligence for personalized nutritional care.

Adipose-derived mesenchymal stem cells (gAD-MSCs) are promising candidates for veterinary regenerative medicine, yet the characterization of gAD-MSCs from locally adapted Indonesian goat breeds remains limited. This study aimed to isolate and characterize gAD-MSCs from Peranakan Ettawa (PE) goats using tissue explant culture. Subcutaneous adipose tissue was collected from the base of the tail of healthy PE goats (n=3). Primary cell outgrowth from explants was observed by Day 5, displaying characteristic fibroblast-like, spindle-shaped morphology and strong plastic adherence. Serial passaging to Passage 3 (P3) yielded a morphologically stable, homogeneous cell population. Assessment of cellular metabolic activity via the resazurin assay demonstrated sustained cell viability and a statistically significant increase in metabolic activity between Day 3 and Day 5 (p < 0.05). Furthermore, functional clonogenic capacity, evaluated using the colony-forming unit (CFU) assay, showed continuous temporal expansion of colonies over 14 days, yielding an average of 52.0 + - 4.1 colonies per dish. These findings confirm that expanded gAD-MSCs P3from PE goats maintain characteristic mesenchymal morphology, sustained metabolic activity, and clonogenic capacity. This work provides a baseline cellular profile of PE goat gAD-MSCs, supporting their potential use in veterinary regenerative medicine and tissue engineering.

Children of undernourished women have impaired pre- and postnatal growth. Undernourished women and children have a high incidence of environmental enteric dysfunction (EED), an enteropathy characterized by gut barrier dysfunction and systemic inflammation. Here, we employ gnotobiotic mice to compare the effects of bacterial consortia cultured from the duodenal microbiota of Bangladeshi women with EED and their healthy counterparts. Female mice harboring the EED-derived consortium exhibited fetal and placental growth restriction. Transcriptomic and proteomic analyses disclosed pronounced effects of the EED-derived consortium on the decidual component of the maternal-fetal interface involving tissue-resident uterine natural killer (uNK) cells and disruption of TGF-{beta} signaling between uNK and decidual stromal cells. Co-housing mice with EED and healthy consortia ameliorated these effects, disclosing bacterial targets to improve prenatal development.