Nutrients

Background: Maternal micronutrient deficiencies (MNDs) and inflammation contribute to adverse birth outcomes While the individual effects of MNDs have been studied, the consequence of co-occurring MNDs remains unclear. Objectives: To examine the associations between maternal micronutrient deficiencies and inflammation with adverse birth outcomes (ABOs). Methods: Data from 5,408 pregnant women across 11 datasets from 10 countries were analyzed. Descriptive analyses explored the distribution of MNDs (iron, vitamin A, zinc, serum folate, vitamin D, and vitamin B12) and inflammation (c-reactive protein >5 mg/L or -(1)-acid glycoprotein > 1g/L) by maternal characteristics (age, height, education, socioeconomic status [SES]) using chi-square tests. Associations of 1) single MNDs and inflammation and 2) co-occurring MNDs (2 deficiencies at a time) with low birth weight (LBW, < 2500 g), preterm birth (PTB, < 37 wks), and small-for-gestational age (SGA, < 10th percentile for gestational age), were examined using modified Poisson regression to estimate relative risk (RR), adjusting for age, SES, and dataset. Results: Young maternal age and short height were associated with up to 9.7% and 25% higher prevalence of MNDs and inflammation, respectively. Lower education and SES level were associated with higher prevalence of Vitamin B12 deficiency. Women with folate deficiency had an increased risk of LBW (RR [95% CI]: 1.22 [1.06, 1.39]). Co-occurring MNDs for folate and vitamin B12 were also associated with increased LBW risk (1.38 [1,1.9]) as was folate deficiency without iron (1.28 [1.09, 1.51]) or vitamin B12 deficiency (1.67 [1.09, 2.56]) compared with mothers without either deficiency. Iron deficiency without vitamin B12 deficiency was associated with a reduced LBW risk (0.4 [0.2, 0.79]). Conclusion: Maternal MNDs, especially folate and vitamin B12, are linked to adverse birth outcomes. Complex nutrient interactions highlight the need to explore these relationships to improve maternal and neonatal health interventions.

Fermented foods are increasingly recognized for their health-boosting potential, yet the mechanisms involved are not fully resolved. Here, we tested whether kombucha reshapes the gastrointestinal microbiome and whether these changes are associated with stress-related behaviors under contrasting dietary backgrounds. Male C57BL/6 mice were fed either a total Western diet (TWD) or a control diet (CTRL) supplemented with kombucha or water three times weekly for seven weeks. Depressive-like and anxiety-related behaviors were evaluated using the forced swimming (FST) and marble burying tests (MBT). Ileum, cecum, and colon microbiomes were profiled via 16S rRNA, ITS2, and shotgun metagenomics, while feces and whole brains were profiled by LC-MS metabolomics. Serum cytokines were measured by ELISA. Results highlight diet-dependent effects of Kombucha on behavioral, microbial and metabolic outcomes. Kombucha reduced immobility in the FST under both diets, whereas fewer marbles buried were observed only under TWD. Kombucha intake enriched Bifidobacterium pseudolongum in the ileum under CTRL and TWD diets, while cecal microbial functions related to amino acid metabolism were stimulated mainly under CTRL. Only CTRL mice receiving kombucha showed higher fecal acetate and butyrate together with lower fecal levels of neurochemically relevant amino acids, including glutamine, phenylalanine, tryptophan, and tyrosine. Under TWD, kombucha was associated with lower spleen weight and altered brain tryptophan/kynurenine profiles. These findings identify kombucha as a food intervention that can remodel gastrointestinal microbial and neuroactive metabolism in a diet depending manner. Associations with reduced depressive and anxiety-related behaviors are promising but warrant further exploration. Key HighlightsO_LIKombucha supplementation reshaped the mice gastrointestinal microbiome and its neuroactive potential C_LIO_LIKombucha intake was associated reduced depressive and anxious like behaviors C_LIO_LIThe potential of kombucha to modulate microbial, metabolic and behavioral outcomes may be dependent on subject dietary background C_LI

Background & AimsHigh-fat diets (HFDs) are a major modifiable risk factor for intestinal health. Current research focuses primarily on palmitate (C16:0); however, myristate (C14:0, rich in dairy products) has been minimally investigated. HFDs increase ceramide generation which drives endoplasmic reticulum (ER) stress; with both sphingolipids and ER stress being key contributors to intestinal biology. Whether different fatty acids uniquely impact sphingolipid metabolism and ER stress in intestinal biology has not been well defined. MethodsHuman colon epithelial cells were utilized to determine the role of ceramide synthases (CerS) 5 and 6 on myristate-induced ER stress using pharmacologic inhibitors and siRNA. Intestinal epithelial cell specific CerS5 and/or CerS6 knockout mice of both sexes were fed a control, high milk-fat, or high lard-fat diet for 16 weeks. Cells and colon tissues were analyzed for lipids, mRNA, and protein. ResultsMyristate treatment increased C14:0-ceramide and induced IRE1-dependent ER stress. Inhibition of CerS suppressed these effects, yet knockdown of CerS5/6, the primary enzymes generating C14:0-ceramide, unexpectedly exacerbated IRE1 activation both in vitro and in vivo, potentially due to depletion of dihydro(dh)sphingosine. ConclusionsCerS are required for myristate-induced IRE1 activation and restoration of the sphingoid base pool provides partial protection from intestinal ER stress. SYNOPSISThis study identifies a new mechanism linking dietary fats to intestinal cell stress. Ceramide synthases drive ER stress triggered by myristate, a dairy-derived fat, while restoring sphingoid bases partially protects cells, revealing a new role for sphingolipids in shaping intestinal responses to diet. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=193 SRC="FIGDIR/small/728542v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@a6e246org.highwire.dtl.DTLVardef@518c0eorg.highwire.dtl.DTLVardef@1c21140org.highwire.dtl.DTLVardef@1fa993e_HPS_FORMAT_FIGEXP M_FIG C_FIG

BackgroundChronic malnutrition in early childhood is a multifactorial condition associated with long-term impairments, yet the physiological and gut microbial pathways underlying differential growth trajectories remain poorly understood. ObjectiveWe aimed to characterize phenotypic growth trajectories and identify the associated gut microbial and body composition signatures in infants during the first year of life. MethodsWe analyzed longitudinal data from birth to 12 months in a South African cohort (Soweto, n=45). Individual linear growth trajectories were modeled using the Jenss-Bayley equation, and children were clustered based on model parameters to identify phenotypic subgroups. Body composition (fat-free mass and fat mass) was measured via deuterium dilution at 6 and 12 months, and gut microbiome development was assessed using 16S rRNA gene amplicons at 4, 6, and 12 months. ResultsWe identified distinct phenotypic subgroups including healthy growth, catch-up growth, and growth faltering, that were obscured at the cohort level. These trajectories diverged most dynamically within the first 6 months of life. Integrated analysis revealed that in the growth faltering cluster, height-for-age and fat-free mass z-scores stabilized between 6 and 12 months, whereas fat mass z-scores (FMZ) declined. This trade-off is consistent with a catabolic state where energy reserves are prioritized for lean tissue and bone growth. Furthermore, at 6 months, the growth faltering cluster was enriched with opportunistic pathobionts (e.g., Paraclostridium). In contrast, the catch-up cluster exhibited a transient enrichment of facultative anaerobes (e.g., Enterobacter), supporting a hypothesis that these oxygen-tolerant taxa may help bridge a transitional microbial state in partially oxygenated or inflamed environments to enable physiological recovery. ConclusionsEarly childhood chronic malnutrition phenotypes in South African infants can be defined by distinct microbial and body composition signatures that diverge within six months of life. Integrated interventions should target both host anabolic state and microbiome transitions to support recovery.

Background The study aimed to estimate healthcare costs associated with malnutrition in Swedish older adults. Methods We conducted a cohort study using data from the population-based Swedish National Study on Aging and Care in Kungsholmen (SNAC-K, N = 2982), a geriatric inpatient cohort of complex patients (N = 7680), and a cohort of individuals with cognitive impairment from the Swedish Register of Cognitive/Dementia Disorders (SveDem, N = 64192). At risk of malnutrition and malnutrition were ascertained by the Mini-Nutritional Assessment in SNAC-K and the geriatric inpatient cohort. In SveDem, body mass index was used for identifying malnutrition. Healthcare resource use was derived from regional and national registers. Associations between malnutrition and healthcare costs in 2024 Swedish kronor (SEK) were analyzed using two-part models and generalized linear regression models, adjusting for demographic and clinical factors. Findings In the community, at risk of malnutrition and malnutrition were associated with an increase in annual healthcare costs of 2267 SEK (95% CI: 64,4469) and 1846 SEK (95% CI: -6802,10493), respectively. In geriatric patients, healthcare costs over 6 months in individuals at risk of malnutrition and individuals with malnutrition were 60205 SEK (45613,74798) and 86619 SEK (68362,104875) higher than those without malnutrition. In people with cognitive impairment, malnutrition was associated with higher annual healthcare costs (22170 SEK, 95% CI: 15152,29188). Interpretation Both at risk of malnutrition and malnutrition are associated with higher healthcare costs in Swedish older adults. The study findings are important for informing future economic evaluations of malnutrition interventions in Swedish older adults.

Objective To assess serum 25-hydroxyvitamin D [25(OH)D] levels in a health examination population in Guiyang, a low-latitude, high-altitude, and cloudy city in southwestern China, and to identify key determinants using machine learning. Methods This retrospective study included 10,931 adults (>20 years) who underwent health checkups at Guiyang First People's Hospital between February 2019 and April 2025. Beyond conventional statistical comparisons, a two-stage machine learning approach was applied: LASSO regression for feature selection, followed by an optimized Random Forest regression model (mtry = 2). SHapley Additive exPlanations (SHAP) were used to quantify variable importance. Results The median serum 25(OH)D level was 36.63 (IQR 24.77,53.17) nmol/L. Vitamin D deficiency (<50 nmol/L) was present in 70.98% of participants, while sufficiency (>75 nmol/L) was only 7.35%. Significantly lower levels were observed in females, in adults aged <30 years (deficiency rate 85.6%), and during spring. The optimized Random Forest model achieved a cross-validated RMSE of 21.427. SHAP analysis revealed a clear hierarchy of importance: age (mean SHAP = 5.604) > season (4.104) > sex (1.533) {approx} BMI (1.501). Conclusion Vitamin D deficiency is highly prevalent in the Guiyang health examination population. Age and season are the dominant determinants, far outweighing sex and BMI. Targeted interventions should focus on young adults, females, and the spring season, especially in regions with similar cloudy highland climates.

Background/Objectives: Children aged 6-24 months are highly vulnerable to malnutrition during conflict because they depend on breastfeeding, complementary feeding and functioning nutrition services. This study assessed nutritional status, socioeconomic correlates, maternal knowledge and primary health care centre (PHCC) nutrition service gaps in Gaza. Subjects/Methods: This cross-sectional study was conducted at Al-Daraj Martyrs Health Centre, one of the remaining functioning PHCCs in Gaza City during the study period, between late August and October 2025. Mother-child pairs were recruited by convenience sampling. Of 276 approached, 200 were included after non-response and exclusion of questionnaires with missing anthropometric data. Data came from structured interviews and medical records; haemoglobin results were available for 55 children. Results: Stunting affected 12.5% of children, underweight 20.1%, wasting 20.8%, and anaemia 63.6% of the haemoglobin-tested subsample. Underweight was associated with household food shortage (p=0.013) and previous malnutrition treatment (p=0.002), wasting with child age category (p=0.0024), and anaemia with paternal unemployment (p=0.020). Maternal knowledge and practice scores were positively correlated (r=0.177, p=0.012), but neither was independently associated with stunting or underweight in adjusted models. PHCC nutrition support was limited, with 71.0% of mothers reporting nurse-provided nutrition advice and 52.5% reporting growth-chart review. Conclusions: In this clinic-based sample from conflict-affected Gaza, malnutrition among children aged 6-24 months was substantial. The overall pattern suggests that nutritional risk was shaped more by structural deprivation and weakened PHCC support than by maternal knowledge alone. These findings underline the need to restore essential nutrition services and improve access to adequate food for young children.

Background: An increasing demand for organic food has risen due to perceived health benefits. Current evidence for the health effects of organic food is limited. Objective: To evaluate the association between organic food purchase as a proxy for organic food consumption and hypertension in a nationally representative population of the US. Methods: This was a cross-sectional study that included 9173 participants aged >= 18 and had available data of both organic food purchase and hypertension from the National Health and Nutrition Examination Survey 2007-2010. Organic food purchase and frequency were obtained from survey questionnaires. Hypertension was defined as having either a systolic BP >= 130 mm Hg/ diastolic BP >= 80 mm Hg, currently taking antihypertensive medication, or self-reported diagnosis of hypertension. We used multivariable logistic regression with sample weights and adjustment of potential confounders to assess associations (adjusted odds ratio [aOR] and 95% confidence intervals [CI]) between organic food purchase and hypertension status. Results: Findings suggest an 11% decrease in odds of hypertension (aOR = 0.89, 95% CI: 0.75-1.06) among organic food purchasers compared to non-purchasers. Lower odds of hypertension were observed across all categories of organic food purchasing frequency, with 13% lower among rarely purchasing organic food (aOR = 0.87, 95% CI: 0.67-1.14), 9% lower (aOR = 0.91, 95% CI: 0.71-1.16) among sometimes purchasing organic food, and 17% lower (aOR = 0.83, 95% CI: 0.55-1.27) among always or mostly purchasing organic food, as compared to those who never purchased organic food. Conclusion: Our findings suggest that organic food purchase, a proxy for organic food consumption, may be associated with lower odds of hypertension. These findings may reflect either the true benefits of organic food consumption, including lower pesticide amounts and higher nutrient content, or the health-seeking behaviors among health-conscious, healthy, and highly educated individuals.

Iron absorption in the small intestine has classically been described by the duodenal DMT1/FPN1 pathway for inorganic non-heme iron, yet emerging evidence suggests that chemically distinct iron forms may use region-specific routes. Nicotianamine (NA), a plant-derived metal chelator, can form NA-iron (NA-Fe) complexes and has been proposed to support intestinal iron absorption through amino acid transporter pathways. However, direct comparisons of transepithelial transfer of inorganic iron and NA-Fe across defined small intestinal regions under controlled epithelial conditions remain limited. Here, we established region-specific 2D epithelial monolayers derived from duodenal and proximal jejunal crypt organoids from male ICR mice cultured on Transwell inserts. Transcriptomic profiling indicated partial retention of regional identity, and barrier integrity was confirmed by junctional marker localization, transepithelial electrical resistance, and low paracellular permeability. We then examined expression and polarized localization of candidate transporters for inorganic iron (Dmt1/Fpn1) and NA-Fe (Pat1/Lat2). Finally, we quantified transepithelial transport using apical loading of isotope-labeled iron (55Fe) or NA-55Fe and measured radioactivity appearing in the basolateral compartment as the primary readout of transepithelial flux. Basolateral appearance of inorganic 55Fe was comparable between duodenum- and proximal jejunum-derived monolayers, whereas NA-55Fe exhibited significantly greater basolateral appearance in proximal jejunum-derived monolayers. These findings demonstrate that organoid derived, region-specific monolayers provide a tractable epithelial platform to evaluate iron form-dependent, region-specific transepithelial transfer and to enable further mechanistic dissection of NA-Fe transport. NEW & NOTEWORTHYNon-heme iron absorption may depend on iron chemical form and intestinal region, but direct epithelial comparisons are scarce. We established duodenum and proximal jejunum derived murine intestinal organoid monolayers on Transwells and quantified transepithelial flux using isotope-labeled iron. Inorganic 55Fe showed no clear regional difference, whereas NA-55Fe displayed greater basolateral appearance in proximal jejunum-derived monolayers. This platform enables mechanistic studies of NA-iron complex transport.

Background: Black adults bear a disproportionate burden of cardiometabolic dysfunction, yet most dietary trial evidence comes from predominantly White cohorts. Objective: To evaluate whether a personalized whole-food dietary intervention improves cardiometabolic outcomes more in Black than White young adults with overweight or obesity. Methods: In this 8-week randomized, controlled trial (ClinicalTrials.gov: NCT04635917), 112 Black and White adults (18-35 years; BMI 25-45 kg/m2) were block-randomized by race to a personalized dietary intervention providing whole foods (PD, n=57) or conventional dietary counseling at baseline (BL) using MyPlate guidelines (CD, n=55). Primary outcomes were Matsuda Index and fasting and OGTT-derived glucose, insulin, and non-esterified fatty acids. Other glucoregulatory, cardiovascular, anthropometric, appetite, and cognitive outcomes were also assessed. Outcomes were analyzed using baseline-adjusted linear models with sensitivity analyses adjusting for baseline BMI and food security score. Results: Compliance with study food consumption was 85-91%. Diet quality was higher in PD than CD (P < 0.05), with larger gains in vegetable-related outcomes among Black participants (group x race, P < 0.05). HOMA-{beta} was lower in PD than CD overall (P < 0.05). In sensitivity analyses, Black PD participants had greater fasting insulin reductions than White, especially in the latter half of intervention (week x group x race, P < 0.05), with a similar tendency for HOMA-IR. Glucose AUC 0-30 min was higher in White than Black PD participants (group x race, P < 0.05). Concentration performance was higher in PD than CD overall (P < 0.05), with larger gains in processing speed and accuracy among Black than White participants (group x race, P < 0.05). No effects were observed for cardiovascular or appetite outcomes. Conclusions: The personalized whole-food intervention produced differential effects in fasting insulin and early-phase glucose handling, and greater benefits in attention, in Black compared with White young adults with overweight or obesity during weight maintenance.

BackgroundNo official correspondence table exists between the Japanese Standard Tables of Food Composition 2020 (8th edition; MEXT) and the USDA FoodData Central (FDC), despite their widespread use in nutritional research. This absence has hindered international comparison of food composition data for over six decades. MethodsWe developed a bidirectional matching pipeline using Claude Haiku (Anthropic), a large language model (LLM), combining food category mapping, 17-nutrient Euclidean distance ranking, and LLM-based conceptual judgment. Survey (FNDDS) data were excluded from FDC, yielding 8,158 items (Foundation Foods and SR Legacy). Matching was performed in both directions: MEXT[-&gt;]FDC and FDC[-&gt;]MEXT. ResultsOf 2,478 MEXT items, 1,927 (77.8%) were matched to FDC items, while 549 (22.2%) had no FDC equivalent (JP-only foods). Of 8,158 FDC items, 5,445 (66.7%) were matched to MEXT items, while 2,698 (33.1%) had no MEXT equivalent (US-only foods). Bidirectional consensus yielded 435 confirmed food pairs across 13 food categories. Notably, FDC items showed systematically higher calcium (+6.0 mg/100g) across 12 of 13 categories, while MEXT items showed systematically higher potassium (-3.7 mg/100g) across 9 of 13 categories and higher vitamin A as RAE (-3.7 g/100g) across 8 of 13 categories. ConclusionsThis study presents the first systematic bidirectional food correspondence table between MEXT and USDA FDC. The 435 confirmed pairs constitute a validated common vocabulary for international food composition research. The systematic cross-national differences in calcium, potassium, and vitamin A represent novel findings with direct implications for international dietary comparison studies. The complete correspondence table (Version 0.1) is openly available at https://github.com/shnkgw-rincom/jbfd-correspondence-table (DOI: 10.5281/zenodo.20103327).

Background: Recent food-based recommendations for flavan-3-ols highlight a growing need to understand the breadth of our dietary polyphenol exposure. However, estimation of dietary polyphenol intake remains challenging, requiring custom computational tools that are often difficult to implement or not fully reproducible. Objective: We aimed to an automated, user-friendly tool to estimate polyphenol intake from diet recalls and records. Methods: We developed Polyphenol Estimator, a tool that processes dietary data from the Automated Self-Administered 24-Hour (ASA24) Dietary Assessment Tool or the Automated Multiple-Pass Method from the National Health and Examination Survey (NHANES). Polyphenol Estimator disaggregates foods using the FDA Food Disaggregation Database into ingredients, matches these ingredients to FooDB, and estimates polyphenol intake at the total, class, and compound level. Optionally, these polyphenol estimates can be used to calculate the Dietary Inflammatory Index (DII). Polyphenol Estimator is freely available online (https://swi1.github.io/polyphenol_estimator) with a tutorial for users with limited programming experience. Results: To illustrate Polyphenol Estimator, we applied it to two days of diet recalls from adults ([&ge;] 20 years) in NHANES 2021-2023 (n = 2778). For 97.7% of participants, less than 2.5% of reported foods went unmapped, with 75.7% of participants having complete mappings. Total polyphenol intake was 517 +/- 439 (mean +/- SD) mg/1000 kcal, largely from green tea, coffee, black tea, apples, wine, oranges, and blueberries. At the class level, polyphenols classified as organooxygen compounds, flavonoids, and cinnamic acids and derivatives were top intake contributors. At the compound level, cyptochlorogenic acid, neocholorogenic acid, and caffeic acid were top contributors. Lastly, the DII was 1.4 +/- 1.9, indicating the average diet had proinflammatory potential. Conclusions: Polyphenol Estimator offers an automated method to obtain total, class, and compound-level polyphenol estimates from dietary data to aid future efforts to understand polyphenol intake exposures and their biological impact on health.

Exclusive breastfeeding (EBF) for the first six months is a critical protective practice, yet determinants beyond knowledge among young mothers in peri-urban sub-Saharan Africa remain insufficiently understood. This facility-based cross-sectional study assessed factors associated with EBF among 413 mothers aged 15-29 attending postnatal services at two public facilities in Lusaka, Zambia (Aug-Oct, 2025). Data from structured interviewer-administered questionnaires covered demographic, socioeconomic, cultural, mental health, peer support, and neonatal care knowledge factors. Logistic regression produced adjusted odds ratios (AOR) with 95% confidence intervals (CI). Although 99.5% reported receiving neonatal care education, 71.6% practiced EBF. Mothers aged 25-29 had lower odds of EBF than those aged 15-19 (AOR = 0.17, 95% CI: 0.03-0.99). Married mothers were more likely to exclusively breastfeed (AOR = 4.83, 95% CI: 1.59-14.65). Separated mothers also showed higher odds (AOR = 13.66, 95% CI: 1.89-98.71), although the wide confidence interval indicates substantial uncertainty and its based on a small subgroup (n=13). Formal employment was positively associated with EBF (AOR = 3.94, 95% CI: 1.12-13.85). Avoidance of specific traditional neonatal practices (AOR = 0.14, 95% CI: 0.04-0.53) and not consulting traditional healers (AOR = 0.06, 95% CI: 0.02-0.18) were also independently associated with EBF. Postnatal anxiety showed a strong inverse association (AOR = 0.14, 95% CI: 0.03-0.76). Parity, income, education, neonatal care awareness, and receipt of health education were not independently associated. These findings suggest that EBF in peri-urban Lusaka is shaped more by social, cultural, and psychological influences than knowledge alone, underscoring the need to integrate mental health screening, culturally sensitive counselling, and family-centred support within postnatal services to improve EBF uptake among young mothers in similar settings.

Estrogen is an essential hormone that critically impacts bodily and brain functions, supporting learning, memory, and motor activities. A decrease in estrogen levels is associated with cognitive decline and motor dysfunction, such as muscle weakness. While conventional hormone replacement treatments (HRT) exist, those have limitations and potentially severe side effects. NAP (davunetide) is the smallest neuroprotective peptide site of activity-dependent neuroprotective protein (ADNP), a master regulator of cognition, essential for brain formation. It is known that NAP restores ADNP activity in cases of deficiency and it has already shown potential in preventing cognitive impairment, protecting against tauopathy, and improving motor function in various animal models and in clinical trials. Based on the dynamic regulation of ADNP by the estrous cycle and its involvement in steroidogenic pathways, we hypothesize that NAP may restore ADNP activity and thus serve as an alternative to conventional hormonal treatments. To test this, 3-month-old female ICR mice underwent bilateral ovariectomy (OVX) or Sham surgery and received daily intranasal administration of NAP, estrogen, or vehicle. Results showed a significant reduction in weight-normalized forelimb grip strength in the OVX model. Daily administration of NAP or estrogen resulted in intermediate grip strength levels that did not statistically differ from either the Sham control or untreated OVX groups. Interestingly, grip strength was the only test that yielded significant results, and no significant differences were observed in the Novel Object Recognition (NOR) test or computed tomography (CT) scans. These findings suggest that NAP may effectively prevent the loss of physical force production typically seen following ovarian hormone depletion, presenting a viable, non-hormonal candidate strategy for managing musculoskeletal symptoms. We hypothesize that the lack of significance in other parameters was due to soy-derived phytoestrogens in the diet, which may have exerted a systemic estrogenic effect that masked the expected physiological phenotypes typically observed in OVX models. Future replication using phytoestrogen-deficient food is required to isolate the specific neuroprotective and musculoskeletal effects of NAP from dietary influence and clarify the broader therapeutic benefits of NAP.

BackgroundIgA is the dominant antibody in the human gut and a key regulator of host-microbe interactions. Infants begin to produce IgA at around 6 months old and receive large quantities of IgA via human milk, but technical limitations have prevented species-level characterization of IgA binding in early life. This has left basic knowledge gaps about which species are targeted by IgA in infancy, and how modifiable lifestyle factors like breastfeeding and complementary feeding impact IgA targeting. ResultsHere we adapt Metagenomic Immunoglobulin Sequencing (MIg-Seq) for low-biomass infant fecal samples and apply this optimized protocol to 32 longitudinal samples from 16 infants enrolled in the MINT trial, a four-arm randomized controlled trial comparing meat-based, dairy-based, plant-based, and reference complementary feeding patterns, with fecal sampling at 6 and 12 months (pre and post intervention). Infant IgA targeting mirrors adults at the phylum level, with both age groups showing significantly higher IgA targeting of Pseudomonadota and lower targeting of Bacteroidota relative to other phyla. During the substantial microbiome compositional shifts noted between 6 and 12 months, IgA targeting is significantly more stable than the microbiome itself. Among persistent colonizers, IgA targeting strengthens significantly from 6 to 12 months, with the most pronounced effect observed for Bifidobacterium, a finding robust across all dietary arms and feeding modes. The feeding arm to which infants were enrolled was not significantly associated with IgA binding, but several nutrient-specific associations were discovered. Animal-derived nutrients, particularly cholesterol, are strongly positively correlated with IgA targeting of Bifidobacterium longum, while plant-derived carotenoids are positively associated with IgA targeting of Flavonifractor plautii and Ruminococcus gnavus. ConclusionsThis study introduces an experimental and computational framework for species-level IgA profiling in the infant gut. The progressive strengthening of IgA targeting of Bifidobacterium and other beneficial persistent colonizers suggests a role for IgA in reinforcing beneficial microbes during infancy. The nutrient-specific dietary effects on IgA targeting reveal the immunological consequences of the complementary feeding period, and highlight a contrast between animal-versus plant-based diets. Together, these findings point to early nutritional interventions and IgA-based therapeutics as promising tools for promoting healthy immune-microbiome development.

Obesity is associated with chronic low-grade systemic inflammation of adipose tissue and is often linked to intestinal epithelial barrier (IEB) dysfunction. The present study aimed to evaluate the effects of in vitro gastrointestinal digests of bovine milk containing A1B or A2 {beta}-casein variants on leaky IEB and adipocyte inflammation. Digests of A1B (DA1B) and A2 (DA2) milk were administered to an in vitro Caco-2/HT-29 intestinal cell co-culture mimicking a leaky gut. Intestinal absorbed fractions derived from A1B (MA1B) and A2 (MA2) were administered to hMADS adipocytes. DA1B and DA2 did not modify intestinal permeability, either in the absence or the presence of inflammation. DA1B reduced Claudin-1 mRNA, as well as zonula occludens-1 mRNA and protein expression. Both DA1B and DA2 increased interleukin-8 expression, but only DA1B increased tumor necrosis factor-. In human adipocytes, MA1B, and to a lesser extent MA2, increased the expression of pro-inflammatory markers monocyte chemoattractant protein-1 and interleukin-6, while reducing adiponectin levels. DA2 preserved in vitro leaky IEB integrity and exhibited a lower inflammatory potential in both leaky gut and adipocytes compared to DA1B. This study is the first to establish a link among A2 milk, leaky gut syndrome, and obesity.

Background and Aims: Diet plays a critical role in managing Crohns disease (CD) inflammation. We assessed whether dietary replacement of animal protein (AnimalP) by soy-pea protein (SoyP) decreases the pro-inflammatory potential of gut microbiota and intestinal inflammation in CD patients. Design: In an open-label, randomized controlled feeding trial at University Hospitals Cleveland Medical Center, CD participants and healthy controls were randomized (1:1) to a soy-pea or animal protein diet for 7-days. Primary outcomes were the absolute difference (d7-d0) in; Crohns Disease Activity Index (CDAI) score and fecal myeloperoxidase (MPO). Secondary outcomes included fecal calprotectin (FC) and high-sensitivity C-reactive protein (hsCRP). Murine fecal transplantation experiments were performed to determine the inflammatory potential of diet-altered gut microbiota. Results: The study randomized 66 participants and 60 were included in the final analysis (n=31 CD, n=29 HC). After 7 days, CD-SoyP participants were more likely than CD-AnimalP to show reductions in HBI (RR=4.68, 95% CI: 1.22-17.98, P=0.009) and fecal MPO (RR=2.30, 95% CI: 1.04-4.85, P=0.032), with a similar directional trend for CDAI (RR=1.52, 95% CI: 0.89-2.58, P=0.135). No participants experienced worsening of CDAI. The rank-based composite CDAI-MPO score was lower in the CD-SoyP vs CD-AnimalP group (median [IQR]: 5 [4-6] vs 8 [7-9]; P=0.012). Stratified analyses showed significant reductions in fecal MPO among CD participants with lower baseline disease activity (CDAI <150; P<0.0001), but not in those with higher activity (P=0.799) Conclusion: Short-term addition of plant-based soy-pea protein within a controlled diet exerted a beneficial, anti-inflammatory effect in CD, with evidence of greater effects among participants with lower baseline disease activity. ClinicalTrials.gov, Number NCT04065048.

Background/ObjectivesNeuroinflammation-driven iron dysregulation and neurotoxic astrocyte polarization are increasingly recognized as interconnected pathological mechanisms in neurodegenerative diseases. Systemic inflammation triggered by strenuous exercise or infection can engage the central nervous system and astrocytic inflammatory responses and perturb iron homeostasis; however, targeted nutritional strategies to counteract these processes remain limited. Inflamate(R) is a multi-component botanical supplement comprising boswellic acids, astilbin, xanthohumol, and cinnamaldehyde, each with documented anti-inflammatory properties. However, whether this combined formulation can modulate the inflammatory-iron metabolic axis and astrocyte phenotypic polarization remains unexplored. This study aimed to investigate the effects of Inflamate(R) on LPS-induced pro-inflammatory gene expression, iron metabolism-related gene regulation, and A1/A2 astrocyte phenotypic polarization in mouse astrocytes. MethodsMouse astrocytes (AWT) were pre-treated with Inflamate(R) (0.0375 g/mL) or DMSO vehicle for 24 h, followed by lipopolysaccharide (LPS; 1 g/mL) stimulation for an additional 24 h. The non-cytotoxic working concentration was determined by morphological assessment, CCK-8 cell viability, and LDH cytotoxicity assays. Expression of 14 target genes spanning pro-inflammatory mediators (NOS2, IL6, C3, COX2, PLA2g15, SOCS3), iron metabolism regulators (FTH1, Hepcidin, TFRC, SLC40A1, RGMa, RGMb), and astrocyte polarization markers (S100A10, GFAP) was quantified by qRT-PCR. ResultsUnder normal culture conditions, Inflamate(R) did not significantly alter the expression of any target gene except S100A10, confirming the absence of baseline cytotoxicity or transcriptional homeostatic perturbation. Upon LPS stimulation, Inflamate(R) selectively suppressed NOS2 (approximately 64% reduction, p < 0.0001), IL6 (approximately 37% reduction, p < 0.0001), and C3 (approximately 47% reduction, p < 0.0001), while COX2, PLA2g15, and SOCS3 remained unaffected. Concurrently, Inflamate(R) significantly reduced LPS-induced Hepcidin expression to approximately 17% of the control level (p < 0.05) and attenuated FTH1 upregulation (p < 0.01), without altering the expression of iron transporters (TFRC, SLC40A1) or BMP-SMAD pathway components (RGMa, RGMb). Furthermore, Inflamate(R) upregulated the neuroprotective A2 marker S100A10 under both basal (p < 0.05) and LPS-stimulated conditions (p < 0.01), while the general reactivity marker GFAP remained unchanged. ConclusionsInflamate(R) exerts a selective, multi-target modulatory effect at the transcriptional level in LPS-stimulated astrocytes, encompassing suppression of the iNOS-NO and IL-6 signaling axes, attenuation of inflammation-driven hepcidin-ferritin iron dysregulation via the IL-6-STAT3 pathway, and promotion of a phenotypic shift from neurotoxic A1 toward neuroprotective A2 astrocyte polarization. Given that the IL-6-JAK-STAT3-hepcidin axis is also activated during exercise-induced systemic inflammation, these findings suggest that Inflamate(R) may represent a targeted nutritional strategy for preserving CNS iron homeostasis and supporting neuroprotective astrocyte function in both neurodegenerative and exercise-related neuroinflammatory contexts. Further validation in in vivo neurodegenerative and exercise models, including protein-level analyses, is warranted to confirm these transcriptional findings.

Ultra-processed food (UPF) may contribute to increased energy intake and weight gain, but evidence synthesis from randomised controlled trials (RCT) is lacking. A pre-registered systematic review and meta-analysis of RCTs was conducted comparing UPF with less processed food (LPF) on energy intake and/or body weight in humans. Secondary analyses (meta-regression and sub-group) examined effects of UPF on appetite sensations, eating rate, palatability and considered the role of nutrient profile in explaining results. Ten eligible studies were included. UPF trial arms tended to have higher energy intake (standardised mean differences [SMDs]=0.18-0.44), but statistical significance varied between analytic models. Weight gain (SMD=0.65) and eating rate (SMD=0.96) were significantly greater in UPF trial arms. No significant differences in palatability, appetite sensations or energy intake later in the day were observed. Diets (UPF vs. LPF) used in trials were not matched for nutrient profile. Effects on energy intake varied if UPFs were higher (SMD=0.71) or similar (SMD=0.02) in energy density. Current RCTs are suggestive that UPFs may increase energy intake and body weight; however, results may be explained by energy density of foods used. Further research is needed to understand whether the level of processing impacts health outcomes independent to nutrient profile.

BackgroundLauric acid (LA) is a medium-chain saturated fatty acid found in several foods, including vegetable oils and seeds. Previous studies have demonstrated that LA exhibits neuroprotective, antioxidant, and anti-inflammatory properties in experimental models of neuropsychiatric disorders. Therefore, the present study aimed to investigate the behavioral and neurochemical effects of LA in a corticosterone-induced murine model of depression. MethodsMale Swiss mice received corticosterone (CORT; 20 mg/kg, subcutaneously) for 23 consecutive days, while the control group received vehicle only. During the last nine days of the experimental protocol, the animals received the respective treatments by oral gavage: LA (10 or 20 mg/kg), fluvoxamine (FLUV; 50 mg/kg), or vehicle, administered 1 hour after CORT injection. One hour after treatment administration, the animals were subjected to the behavioral tests: Forced Swimming Test (FST), Tail Suspension Test (TST), and Open Field Test (OFT). At the end of the experimental protocol, the animals were euthanized, and the prefrontal cortex (PFC), hippocampus (HPC), and striatum (STR) were collected for neurochemical analyses. ResultsChronic CORT treatment significantly increased immobility time in the FST and TST, characterizing depressive-like behavior. Treatment with LA reversed these behavioral alterations, showing an effect similar to that observed in the FLUV-treated group. In the OFT, LA did not promote significant changes in locomotor activity, suggesting the absence of psychostimulant effects. Regarding neurochemical analyses, LA treatment did not reduce malondialdehyde (MDA) or nitrite/nitrate (NO2-/NO3-) levels, nor did it alter reduced glutathione (GSH) levels in the evaluated brain regions. ConclusionThe results demonstrated that LA treatment was able to reverse corticosterone-induced behavioral alterations in mice, indicating a potential antidepressant-like effect. Furthermore, the observed effects were not associated with nonspecific locomotor alterations. Although LA did not promote significant changes in the evaluated neurochemical markers, these findings reinforce its potential as a therapeutic agent for depressive disorders and highlight the need for further studies to elucidate its mechanisms of action and possible clinical applicability.