bluuebunny/crossref_metadata_2025_split huggingface dataset:
Term Infant Formula Supplemented with Human Milk Oligosaccharides (2′Fucosyllactose and Lacto‐N‐neotetraose) Shifts Stool Microbiota and Metabolic Signatures Closer to that of Breastfed Infants
Authors: Steenhout Philippe , Sperisen Peter , Martin François‐Pierre , Sprenger Norbert , Wernimont Susan , Pecquet Sophie , Berger Bernard 
Published: November 2023

Human milk oligosaccharides (HMOs) may provide benefits to formula‐fed infants in part by influencing the establishment of the intestinal microbiota. We evaluated effects of infant formula with 2 HMOs (2′Fucosyllactose [2′FL] and Lacto‐N‐neotetraose [LNnT]) on the early intestinal microbiota in infants (ClinicalTrials.gov NCT01715246).Healthy term infants ages 0–14 days were randomly assigned to intact protein cow's milk‐based infant formula (Control, n 87) or the same formula with 1.0 g/L 2′FL and 0.5 g/L LNnT (Test, n 88); a reference group of breastfed infants was also included (n 38). Stool samples were collected at age 3 months for assessment of microbiota using 16S rRNA gene sequencing and metagenomics; metabolic signature was assessed using proton NMR‐based metabolite profiling.The global average microbial composition profile, established for infants with available stool samples who had adhered to the study protocol, showed a similar pattern for Control (n 65) and Test (n 58) at the genus level, although Test was closer to breastfed (n 34) than Control. Calculation of microbial alpha diversity and comparison of the global microbiota composition using random permutations of the redundancy analysis (RDA) confirmed that Test was different from Control at the genus level (p<0.001) and closer to the breastfed group. Statistical analyses identified several taxa differentially present in Control and Test: Bifidobacterium (p=0.01), Escherichia (p=0.008), unclassified Coprobacillaceae (p=0.01), unclassified Peptostreptococcaceae (p=0.026), Dorea (p=0.033), and Megamonas (p=0.035). Correction for False Discovery Rate confirmed the first three observations. Main discriminants between Test and Control by random forest analysis were Bifidobacterium, Escherichia and Peptostreptococcaceae. Clinically relevant pathogens were rare; however, Clostridium difficile toxin A/B was detected in 14% of Test and 26% of Control (OR 0.47, CI 0.17–1.27, p=0.15). Multivariate analysis identified phenylalanine, isoleucine, tyrosine, fecal organic acids and fucosylated compounds as influential metabolites that discriminated between the Test, Control and breastfed groups. Globally, the values observed in Test were more similar to those observed in the breastfed group compared with Control, a finding that may indicate reduced protein fermentation.Together these findings indicate that the addition of 2′FL and LNnT to a starter infant formula shifts the stool microbiota and metabolic signature towards those observed in breastfed infants, both in several aspects of composition and function. Further studies are warranted to evaluate whether such a shift in gut ecology towards the breastfed standard leads to health benefits.Support or Funding InformationThe study was funded by Nestec S.A.
Metabolic Phenotype and Increased Adiposity in a Mouse Model of Chronic Gestational Alcohol Exposure
Authors: Amos‐Kroohs Robyn M , Nelson David W , Yen Chi‐Liang Eric , Smith Susan M 
Published: November 2023

Fetal Alcohol Spectrum Disorder (FASD) is the largest preventable cause of neurodevelopmental disability and recent studies suggest that prenatal alcohol exposure (PAE) also increases obesity risk at adolescence. Children with FASD exhibit hyperphagia and have inappropriate dietary intake which may contribute to increased obesity risk. We developed a mouse model of gestational binge alcohol exposure (PAE) to delineate the contributions of metabolic dysregulation, eating behavior and diet response in offspring to increased obesity risk. Pregnant C57Bl/6J females were gavaged with 3 g/kg alcohol (EtOH) daily from gestational day (GD) 12.5 to 17.5 in two half doses, two hours apart. Isocaloric maltodextrin (MD) and medium chain triglycerides (MCT) were included as nutritional controls. A sham (H2O) treatment was used to control for gavage stress. At 17 weeks, sex matched pairs from each litter were investigated for the following endpoints: obesity via dual‐energy X‐ray absorptiometry (DXA), carbohydrate metabolism using glucose tolerance testing (GTT), blood pressure and heart rate using arterial probes as well as indirect calorimetry in metabolic cages. Although lighter during lactation, EtOH pups gained significantly more weight post‐weaning than MD and MCT groups (p<0.05). EtOH offspring have increased fat mass compared with other groups at 17 weeks (p<0.05) by DXA. Male EtOH, MD, and MCT offspring exhibited increased basal glucose levels and significantly increased tolerance during GTT in comparison with H2O offspring (p<0.05) despite similar weights between groups. EtOH offspring have increased systolic blood pressure (p<0.05) and heart rate (p<0.05). In metabolic chambers, all offspring were challenged with high sugar (70%) and high fat (60%) diets. Metabolic parameters such as food intake, VO2, and respiratory exchange ratio were similar between groups, although slight differences were found in feeding behavior patterns and food intake during diet challenges between EtOH and all control groups. After a month on high fat diet, male EtOH offspring have exacerbated weight and fat mass gain (p<0.05). After a month on high fat diet, female EtOH offspring exhibit significantly increased basal glucose levels (p>0.05) and increased glucose tolerance during GTT. Taken together, these data suggest that PAE may be associated with a metabolic syndrome. Up to 1 in 3 women report drinking during pregnancy, so PAE may be a previously unrecognized factor for increased obesity risk in the context of an obesogenic environment.Support or Funding InformationAA22999. AA11085, 2T32DK007665
Effects of DHA & Choline Supplementation on Developmental Outcomes of the Typically Developing and Fetal Alcohol Exposed Rat Pup
Authors: Canipe L Grant , Jackson Thomas W , Cheatham Carol L 
Published: November 2023

ObjectiveFetal Alcohol Exposure (FAE) causes a range of neurodevelopmentally abnormal phenotypes. Effects on hippocampus and frontal lobe, areas that preferentially accrete docosahexaenoic acid (DHA), are seen consistently, possibly due to changes to the epigenome during gestation. DHA and choline play an integral role in neural development and subsequent cognitive function, but their effects are generally studied in isolation. Recent work in our lab has shown that DHA and choline act together in support of infant and toddler cognition. Thus, a nutritional intervention using a combination of DHA and choline may have promise for the amelioration of FAE. The primary goal of this study was to examine the effects of DHA and choline supplementation on development in typically‐developing and alcohol‐exposed pups. The secondary goal was to evaluate the feasibility of DHA and choline as a prenatal supplement for rat dams by designing a supplemented liquid‐ethanol diet.MethodsRat dams were randomly assigned to four treatment groups, with EtOH and/or DHA & choline (S) (EtOH, EtOH‐S, pair‐fed, and pair‐fed‐S), and a fifth group added as ad libitum control. The experimental diet was administered from gestational day 5 to 20. Diet was isocaloric (~100 cal/day/rat) with 35% of daily calories supplied by either EtOH or maltose dextrin. Dams were supplemented daily with DHA (10.8 mg) and choline (155 mg). Food intake was measured for the EtOH‐fed dams; weight‐matched dams were fed this amount (pair‐fed). On postnatal day 2 through 21, markers for development were assessed on bar‐holding and negative geotaxis in pups (n=65). Days to first success (latency) on each test were used as a measure of development.ResultsWe successfully developed a palatable DHA‐ and choline‐supplemented liquid diet. PROC GLM (SAS Ver 9.4) was used to test group differences. FAE resulted in significantly longer latency to success on bar‐holding in EtOH compared to pair‐fed and control animals (p<0.001). There were no significant differences in latencies on either task between the EtOH‐S group and pair‐fed‐S. The EtOH‐S group had significantly shorter latency on both tasks than did the EtOH group (all p<0.001). Finally, there were no significant differences between the EtOH‐S group and the ad libitum control (p<0.10 with the trend in favor of EtOH‐S), and both performed significantly better than the EtOH group (p<0.01).ConclusionThe mitigating effect of DHA and choline supplementation on FAE shows promise and warrants further investigation. The addition of an ad libitum supplemented group is needed to strengthen our conclusion. However, the data suggest a positive developmental impact of DHA & choline supplementation on the typically‐developing and alcohol‐exposed fetus.Support or Funding InformationNIAAA K01‐AA021134
Intake of Genistein and Daidzein Ameliorates Adiposity and Metabolic Syndrome in High Fat Fed C57BL/6J Mice
Authors: Luo Ting , Miranda Omar , Adamson Allysa , Shay Neil F 
Published: November 2023

IntroductionGenistein and daidzein are isoflavones abundant in soybean. These isoflavones have been shown to have a weak but significant estrogenic effect and other studies have shown isoflavones may impact cancer and metabolic disease. Our prior research (Luo et al. 2014) indicated metabolic improvements in male mice fed a high‐fat (HF) diet supplemented with Novasoy, a dietary supplement containing a mixture of soy isoflavones. With two related, but slightly different chemical structures, it is plausible that dietary genistein and daidzein influence metabolism differently.ObjectiveThe objective of the present study was to determine if diet supplementation with genistein (G) or daidzein (D) would have a differential impact on body weight, body composition, and other physiologic and metabolic parameters in high‐fat fed male C57BL/6J mice.MethodsC57BL/6J mice (n=8 per group) were provided either low‐fat diet (LF, 10% kcal fat), high‐fat diet (HF, 45% kcal fat), or HF plus ~0.2% of either G or D for 10 weeks. Dietary levels of isoflavones are equivalent to intake of dietary supplements in humans. Body weight was recorded weekly and food intake bi‐weekly.ResultsDietary supplementation with G or D led to decreased body weight compared to HF‐fed mice. Furthermore, body weight gain in G‐fed mice was profoundly impacted and lower in value vs. all groups including LF‐fed mice, weight gains were as follows: LF: 7.0 ± 0.6 g, HF: 18.6 ± 1.0 g, G: 2.9 ± 0.7 g, D: 11.9 ± 1.4 g. In glucose tolerance testing, both G and D intake were associated with a trend of decreased area under the curve (AUC), consistent with improved glucose sensitivity vs. HF‐fed mice. Serum insulin levels were consistent with this finding, with concentrations in G‐fed mice significantly lower than HF‐fed and equivalent to LF‐fed mice (P < 0.01). Serum resistin concentrations showed a trend of lower levels vs. HF‐fed mice in G‐ and D‐fed mice (P < 0.01). Serum MCP‐1 levels were measured by ELISA and G‐fed mice had trended to lower MCP‐1 levels compared to HF‐ and D‐fed mice (P < 0.10). Liver tissue sections were evaluated for fat content and relative fat content was LF: 9.0 ± 1.7 %, HF: 30.8 ± 3.8 %, G: 15 ± 3.7 %, D: 30 ± 6.3 %. Hepatic gene expression levels were measured by RT‐PCR, and G‐fed mice had higher levels of several genes related to lipid metabolism including stearoyl‐CoA desaturase‐1 and sterol regulatory element‐binding protein 1a.ConclusionThe profound impact of genistein intake on weight gain was unanticipated and needs to be further explored to determine if it may be of use as a dietary supplement to help promote weight loss or to help improve glucose sensitivity.Support or Funding InformationOregon Agricultural Experiment Station
Adherence to a Mediterranean Diet, and Effects on Cardiometabolic Health in Older Australians; Results from the Mediterranean Diet for Cognition and Cardiovascular Health in the Elderly (MedLey) Trial
Authors: Davis Courtney Rose , Bryan Janet , Wilson Carlene , Hodgson Jonathan , Woodman Richard , Murphy Karen 
Published: November 2023

The MedLey study aimed to assess the impact of adherence to the Mediterranean diet (MedDiet) for six months on cardiometabolic health indicators in a population of older Australian adults. We recruited 166 healthy male and female (57% female) adults aged 65 years or older. Volunteers were randomly allocated (stratified on gender, age and BMI) into either a control group (habitual diet) (n=81) or the MedDiet group (n=85). We measured adherence using a 15‐point MedDiet adherence score (higher scores reflect higher adherence) based on dietary intake data collected using 3‐day weighed food records completed at baseline, two and four months. Cardiometabolic measures included fasting plasma lipids, high‐sensitivity C‐reactive protein (hs‐CRP), F2‐isoprostanes, glucose, insulin and blood pressure (not presented here). These were measured at baseline and after three and six months. We used a simple linear mixed effects model to compare groups over time.Seventy volunteers in the MedDiet group and 67 in the HabDiet group completed the study and were included in the analysis. Adherence scores at baseline were 7.1 and 7.4 for the MedDiet and HabDiet groups, respectively (P for between group difference =0.424). Adherence in the MedDiet group significantly increased by 2.1 (SEM 0.37) points at two months and 2.6 (SEM 0.37) points at four months relative to the control (P <0.001). There was an overall significant effect of diet over the 6 months on triglycerides and plasma F2‐isoprostanes (P<0.05 for between group interaction for both). In the MedDiet group, compared to the HabDiet group, after adjustment for baseline values, mean (SEM) triglyceride concentrations were significantly lower at three (−0.149 (0.04) mmol/L, P<0.001) and six months (−0.094 (0.04) mmol/L, P<0.05), and F2‐isoprostane concentrations were significantly lower at three (−103 (25.9) pmol/L, P<0.001) and 6 months (−65.4 (26.4), pmol/L, P=0.013). There were no significant differences between groups for total, HDL or LDL cholesterol, hs‐CRP, glucose or insulin.Increased adherence to the MedDiet resulted in a significantly lower F2‐isoprostanes over six months, indicating a positive effect on oxidative damage to lipids in vivo. Triglyceride concentrations were also lower with the MedDiet, but the MedDiet had little effect on glycaemic control, hs‐CRP or circulating cholesterol concentrations.Support or Funding InformationThis project was supported by a grant from the National Health Medical Research Council of Australia. Sponsor Prof Linda Tapsell, American Society Nutrition, Affiliation, ltapsell@uow.edu.au.
Effects of omega‐3 supplementation during pregnancy and youth on neurodevelopment and cognition in childhood: a systematic review and meta‐analysis
Authors: Shulkin Masha L , Pimpin Laura , Bellinger David , Kranz Sarah , Duggan Christopher , Fawzi Wafaie , Mozaffarian Dariush 
Published: November 2023

BACKGROUNDLong‐chain omega‐3 fatty acids are thought to be crucial for optimal neurodevelopment in early life.OBJECTIVESTo investigate the effect of omega‐3 supplementation during pregnancy and infancy on child cognitive and developmental outcomes.METHODSWe searched PubMed, Cochrane Library, EMBASE, and PsychInfo through May 2015 without language or publication year restrictions for randomized controlled trials (RCTs) of omega‐3 supplementation (>3 months) i.e. docosahexanoic acid (DHA) and eicosapentaenoic acid (EPA), and quantitative measure of neurodevelopment or cognition. Full‐text inclusion decisions and data extractions were performed independently and in duplicate. Our primary outcome was the standardized mean difference in Bayley Scales of Infant Development (BSID) score between intervention groups in RCTs. Other outcomes included the Weschler Intelligence Scale for Children, Weschler Preschool and Primary Scale of Intelligence, Kaufman Brief Intelligence Test, Kaufman Assessment Battery for Children, Peabody Picture Vocabulary Test, and other standardized measures.RESULTSAmong 571 abstracts, we identified 15 trials with 20 intervention arms involving 2,525 children. Trials used DHA + EPA (N=6 arms), DHA only (N=2), DHA + arachidonic acid (AA) (N=10), or DHA + EPA + AA (N=2); either prenatally (mean 20 weeks gestation; N=4 arms) or within the first few days of birth (N=16). Mean supplementation duration was 7.3 months; and age at outcome assessment, 16 months. In pooled analyses, both maternal and infant supplementation similarly improved neurodevelopment: standardized mean difference (SMD) in BSID= 0.21 (95% CI: 0.01, 0.41) and 0.24 (0.00, 0.48) respectively (Figure 1). Among BSID subscales, DHA and/or EPA raised the psychomotor developmental index (N=8 arms; SMD 0.40; 95% CI: 0.10, 0.70), while DHA + AA raised the mental developmental index (N=15 arms; SMD 0.17; 95% CI: 0.00, 0.35). Pooled findings for other outcomes will be presented.CONCLUSIONOmega‐3 supplementation during either pregnancy or infancy improves child neurodevelopment. These findings indicate the importance of sufficient polyunsaturated fatty acid intake by pregnant women and young children.Support or Funding InformationBill & Melinda Gates Foundation
Feeding a Maternal Diet Enriched in Docosahexaenoic Acid to Lactating Dams Improves the Ex Vivo Tolerance Response to Egg Protein in Suckled Pups
Authors: Richard Caroline , Lewis Erin D , Goruk Suzan , Field Catherine J 
Published: November 2023

An important T cell mediated process that occurs early in life is the development of oral tolerance (OT). Food allergies are believed to be the result of a failure to develop OT to a dietary antigen. The objective of this study was to determine the effect of feeding a maternal diet supplemented with docosahexaenoic acid (DHA) while containing adequate amounts of arachidonic acid (AA) during the suckling period on the development of the immune system and OT in offspring.Sprague‐Dawley dams were randomized to one of the two nutritionally adequate experimental diets 24–48h prior to parturition: control diet (N=12, 0.4% AA and 0% DHA of total fatty acids) or high DHA diet (N=8, 0.4% AA and 0.9% DHA of total fatty acids). Diets were fed to dams ad libitum throughout the suckling period (21 days) and matched for macronutrient, micronutrient and fatty acid content differing only in the composition of omega‐3. At 14‐days pups from each dam were randomly assigned to a mucosal OT challenge for 5 days: placebo (sucrose) or ovalbumin (OVA). At 3 weeks, pups were euthanized and immune cell phenotypes and cytokine production by mitogen‐ (Concanavalin A (ConA), lipopolysaccharide (LPS)) or OVA‐stimulated splenocytes were measured by direct immunofluorescence assay and ELISA, respectively.Feeding dams a high DHA diet increased the proportion of DHA and AA found in breast milk vs. the control diet (both P<0.01). Regardless of the OT challenge, feeding a high DHA diet led to a higher production of interferon‐γ by splenocytes stimulated with ConA and a higher production of interleukin (IL)‐6, IL‐10 and tumor necrosis factor‐α after LPS stimulation (all P<0.05). OVA‐stimulated splenocytes from suckled pups fed the high DHA diet produced significantly more IL‐10 and less transforming growth factor‐β compared to the control diet (both P<0.02), suggestive of better OT. The OT challenge with OVA resulted in a lower production of IL‐6 by LPS‐stimulated splenocytes and led to a higher proportion of cytotoxic T cells expressing CD28 and total cells expressing CD27 (all P<0.02) compared to non‐tolerized pups.Our results suggest that feeding a maternal diet enriched in DHA during the suckling period improves the ability of splenocytes to respond ex vivo to mitogens and the tolerance response to a dietary antigen. Irrespective of the suckling diet, pups who had been orally tolerized to OVA had a lower response to a bacterial antigen despite the presence of more activated T cells and memory immune cells.Support or Funding InformationSupported from the Natural Sciences and Engineering Research Council of Canada. CR holds a scholarship from Canadian Institutes for Health Research and Fonds de recherche en santé du Québec.
Transgenic Up‐Regulation Of Claudin‐6 Decreases Diesel Particulate Matter (DPM)‐Induced Pulmonary Inflammation
Authors: Bodine Jared , Gassman Jason , Milner Dallin C. , Lewis Adam , Dunaway Todd , Egbert Kaleb , Christiansen Connor , Christiansen Andrew , Monson Troy , Broberg Dallin , Arroyo Juan , Reynolds Paul R 
Published: November 2023

Cldn6 is a tetraspanin transmembrane protein found in tight junctional complexes and is implicated in maintaining lung epithelial barriers. In the present study, we tested the hypothesis that abundant Cldn‐6 influences inflammation in mice exposed to acute environmental diesel particulate matter (DPM). Mice were subjected to ten exposures of nebulized DPM over a period of 20 days via a nose only inhalation system (Sireq industries). Using real time RT‐PCR, we discovered that the Cldn6 gene was up‐regulated in control mice exposed to DPM but DPM significantly decreased Cldn‐6 expression in lung‐specific transgenic mice that up‐regulate Cldn‐6 (Cldn‐6 TG). DPM caused increased cell diapedesis into bronchoalveolar lavage fluid (BALF) obtained from control mice, however, Cldn‐6 TG mice had less total cells in BALF following DPM exposure. Because Cldn‐6 TG mice diminished cell diapedesis, other inflammatory intermediates were screened in order to characterize the impact of increased Cldn‐6 on inflammation. In summary, MAPKs, NF‐kB and cytokines including TNF‐alpha and IL‐1beta were all differentially regulated in Cldn6 TG mice and controls following DPM exposure. These results demonstrate that epithelial barriers organized by Cldn‐6 mediate, at least in part, diesel‐induced inflammation. Further work may show that Cldn‐6 is a key target in understanding pulmonary epithelial gateways exacerbated by environmental pollution.Support or Funding InformationThis work was supported by a grant from the Flight Attendant's Medical Research Institute (FAMRI, PRR) and a BYU Mentoring Environment Grant (PRR).