Search

Bioactive ingredients for infant formula have been sought to reduce disparities in health outcomes between breastfed and formula-fed infants. Traditional food safety methodologies have limited ability to assess some bioactive ingredients. It is difficult to assess the effects of nutrition on the infant immune system because of coincident developmental adaptations to birth, establishment of the microbiome and introduction to solid foods, and perinatal environmental factors. An expert panel was convened to review information on immune system development published since the 2004 Institute of Medicine report on evaluating the safety of new infant formula ingredients and to recommend measurements that demonstrate the safety of bioactive ingredients intended for that use. Panel members participated in a 2-d virtual symposium in November 2020 and in follow-up discussions throughout early 2021. Key topics included identification of immune system endpoints from nutritional intervention studies, effects of human milk feeding and human milk substances on infant health outcomes, ontologic development of the infant immune system, and microbial influences on tolerance. The panel explored how "nonnormal" conditions such as preterm birth, allergy, and genetic disorders could help define developmental immune markers for healthy term infants. With consideration of breastfed infants as a reference, ensuring proper control groups, and attention to numerous potential confounders, the panel recommended a set of standard clinical endpoints including growth, response to vaccination, infection and other adverse effects related to inflammation, and allergy and atopic diseases. It compiled a set of candidate markers to characterize stereotypical patterns of immune system development during infancy, but absence of reference ranges, variability in methods and populations, and unreliability of individual markers to predict disease prevented the panel from including many markers as safety endpoints. The panel's findings and recommendations are applicable for industry, regulatory, and academic settings, and will inform safety assessments for immunomodulatory ingredients in foods besides infant formula.

There is a strong rationale for investigating nutritional interventions with docosahexaenoic acid (DHA) in cancer prevention and therapy; however, the effects of DHA on ovarian cancer (OC) have not...

Background and Aims Increasing evidence supports the role of early-life gut microbiota in developing atopic diseases, but ecological changes to gut microbiota during infancy in relation to food sensitization remain unclear. We aimed to characterize and associate these changes with the development of food sensitization in children. Methods In this observational study, using 16S rRNA amplicon sequencing, we characterized the composition of 2844 fecal microbiota in 1422 Canadian full-term infants. Atopic sensitization outcomes were measured by skin prick tests at age 1 year and 3 years. The association between gut microbiota trajectories, based on longitudinal shifts in community clusters, and atopic sensitization outcomes at age 1 and 3 years were determined. Ethnicity and early-life exposures influencing microbiota trajectories were initially examined, and post-hoc analyses were conducted. Results Four identified developmental trajectories of gut microbiota were shaped by birth mode and varied by ethnicity. The trajectory with persistently low Bacteroides abundance and high Enterobacteriaceae/Bacteroidaceae ratio throughout infancy increased the risk of sensitization to food allergens, particularly to peanuts at age 3 years by 3-fold (adjusted odds ratio [OR] 2.82, 95% confidence interval [CI] 1.13–7.01). A much higher likelihood for peanut sensitization was found if infants with this trajectory were born to Asian mothers (adjusted OR 7.87, 95% CI 2.75–22.55). It was characterized by a deficiency in sphingolipid metabolism and persistent Clostridioides difficile colonization. Importantly, this trajectory of depleted Bacteroides abundance mediated the association between Asian ethnicity and food sensitization. Conclusions This study documented an association between persistently low gut Bacteroides abundance throughout infancy and sensitization to peanuts in childhood. It is the first to show a mediation role for infant gut microbiota in ethnicity-associated development of food sensitization.

Given the focus on developing Dietary Reference Intakes (DRIs) based on chronic disease risk reduction and recent research for omega-3 long chain PUFA since the last DRI review, the Canadian Nutrition Society convened a panel of stakeholders for a 1-day workshop in late 2019. Attendees discussed the new NASEM guidelines for establishing DRI values based on chronic disease risk endpoints and the strength of current evidence for EPA and DHA as it relates to the new guidelines. Novelty: Summarizes evidence and expert opinions regarding the potential for reviewing DRI values for EPA and DHA and cardiovascular disease risk and early development.

Stearoyl-CoA desaturase-1 (SCD1) is a key enzyme in the biosynthesis of monounsaturated fatty acids, and the expression of the Scd1 gene is induced by the intake of the lipogenic sugar fructose. We examined the effects of a high-fructose diet on hepatic acetylation of histones H3 and H4 and the binding of carbohydrate response element-binding protein (ChREBP) on the Scd1 gene promoter in rats. Rats were fed a control diet or a high-fructose diet for 10 days. The intake of a high-fructose diet significantly increased histone H3 and H4 acetylation and ChREBP binding to the Scd1 gene promoter as well as the amount of triglyceride and the expression of the Scd1 gene. These results suggest that short-term intake of high fructose upregulates expression of Scd1 by enhancing acetylation of histones H3 and H4 and binding of ChREBP at the Scd1 promoter.

Background Polyunsaturated fatty acids (PUFAs) may influence immune development. We examined the association of PUFAs in human milk with food sensitization and atopic dermatitis among breastfed infants. Methods In a selected subgroup of 1109 mother-infant dyads from the CHILD Cohort Study, human milk was analyzed by gas-liquid chromatography to quantify PUFAs including arachidonic acid (ARA) and docosahexaenoic acid (DHA). At 1 year of age, food sensitization was determined by skin-prick testing for egg, peanut, cow's milk, and soybean, and atopic dermatitis was diagnosed by pediatricians. Logistic regression analyses controlled for breastfeeding exclusivity, family history of atopy, and other potential confounders. Results Overall, 184 infants (17%) were sensitized to one or more food allergens and 160 (14%) had atopic dermatitis. Sex-specific associations were observed between these conditions and milk PUFAs. Girls receiving human milk with lower proportions of DHA had lower odds of food sensitization (aOR 0.35; 95% CI 0.12, 0.99 for lowest vs highest quintile), and a clear dose-dependent association was observed for the ARA/DHA ratio (aOR 2.98; 95% CI 1.10, 8.06 for lowest vs highest quintile). These associations were not seen in boys. Similar sex-specific tendencies were observed for atopic dermatitis. Conclusions Human milk PUFA proportions and their ratios are associated with infant atopic conditions in a sex-specific manner. In female infants, a higher ratio of ARA/DHA may reduce the risk of food sensitization and atopic dermatitis. Further research is needed to determine the underlying mechanisms and clinical relevance of this sex-specific association.

Background Accumulating evidence suggests that the metabolic effects of metformin and fermentable fibers are mediated, in part, through diverging or overlapping effects on the composition and metabolic functions of the gut microbiome. Pre-clinical animal models have established that the addition of fiber to metformin monotherapy improves glucose tolerance. However, possible synergistic effects of combination therapy (metformin plus fiber) have not been investigated in humans. Moreover, the underlying mechanisms of synergy have yet to be elucidated. The aim of this study is to compare in adolescents with obesity the metabolic effects of metformin and fermentable fibers in combination with those of metformin or fiber alone. We will also determine if therapeutic responses correlate with compositional and functional features of the gut microbiome. Methods This is a parallel three-armed, double-blinded, randomized controlled trial. Adolescents (aged 12–18 years) with obesity, insulin resistance (IR), and a family history of type 2 diabetes mellitus (T2DM) will receive either metformin (850 mg p.o. twice/day), fermentable fibers (35 g/day), or a combination of metformin plus fiber for 12 months. Participants will be seen at baseline, 3, 6, and 12 months, with a phone follow-up at 1 and 9 months. Primary and secondary outcomes will be assessed at baseline, 6, and 12 months. The primary outcome is change in IR estimated by homeostatic model assessment of IR; key secondary outcomes include changes in the Matsuda index, oral disposition index, body mass index z-score, and fat mass to fat-free mass ratio. To gain mechanistic insight, endpoints that reflect host-microbiota interactions will also be assessed: obesity-related immune, metabolic, and satiety markers; humoral metabolites; and fecal microbiota composition, short-chain fatty acids, and bile acids. Discussion This study will compare the potential metabolic benefits of fiber with those of metformin in adolescents with obesity, determine if metformin and fiber act synergistically to improve IR, and elucidate whether the metabolic benefits of metformin and fiber associate with changes in fecal microbiota composition and the output of health-related metabolites. This study will provide insight into the potential role of the gut microbiome as a target for enhancing the therapeutic efficacy of emerging treatments for T2DM prevention. Trial registration ClinicalTrials.gov NCT04578652. Registered on 8 October 2020.

To determine the effect of feeding buttermilk-derived choline metabolites on the immune system development in Sprague–Dawley rat pups. Sprague–Dawley dams were randomized to one of the three diets containing 1.7 g/kg choline: 1-Control (100% free choline (FC)), 2-Buttermilk (BM, 37% phosphatidylcholine (PC), 34% sphingomyelin (SM), 17% glycerophosphocholine (GPC), 7% FC, 5% phosphocholine), and 3-Placebo (PB, 50% PC, 25% FC, 25% GPC) until the end of the lactation period. At weaning, pups continued on the same diet as their mom. Cell phenotypes and cytokine production by mitogen-stimulated splenocytes isolated from 3- and 10-week-old pups were measured. At 3 weeks, BM-pups had a higher proportion of cytotoxic T cells (CTL; CD3 + CD8 +) while both BM- and PB-pups had an increased proportion of cells expressing CD28 + , CD86 + and CD27 + (all p > 0.05). Following ConA stimulation, splenocytes from BM- and PB-pups produced more TNF-α and IFN-γ and after LPS stimulation produced more IL-10 and TNF-α (all p > 0.05). Starting at week 6 of age, BM-pups had a higher body weight. At 10 weeks, both the BM- and PB-pups had a higher proportion of CTL expressing CD27 + . After ConA stimulation, splenocytes from BM- and PB-pups produced more IL-2, IFN-γ and IL-6 and more IL-10 after LPS stimulation (all p > 0.05). The proportion of lipid soluble forms of choline in the diet during lactation and weaning periods influence the immune system development in rat offspring.

Background The effects of dietary macronutrients on orexigenic and anorexigenic hormones in children are poorly understood. Objective To explore effects of varying dietary macronutrients on appetite-regulating hormones [acyl ghrelin (AG) and desacyl ghrelin (DAG), glucagon-like peptide 1 (GLP-1), peptide tyrosine tyrosine (PYY) and insulin] in children with PWS and healthy children (HC). Design Randomized, cross-over experiments compared two test diets [high protein-low carbohydrate (HP-LC) and high protein-low fat (HP-LF)] to a STANDARD meal (55% carbohydrate, 30% fat, 15% protein). Experiment 1 included ten children with PWS (median age 6.63 years; BMI z 1.05); experiment 2 had seven HC (median age 12.54 years; BMI z 0.95). Blood samples were collected at baseline and at 60-minute intervals for 4 hours. Independent linear mixed models were adjusted for age, sex and BMI z-score. Results Fasting and post-prandial AG and DAG concentrations are elevated in PWS children; the ratio of AG/DAG is normal. Food consumption reduced AG and DAG concentrations in both PWS and HC. GLP-1 levels were higher in PWS after the HP-LC and HP-LF meals than the STANDARD meal (P = .02-0.04). The fasting proinsulin to insulin ratio (0.08 vs 0.05) was higher in children with PWS (P = .05) than in HC. Average appetite scores in HC declined after all three meals (P = .02) but were lower after the HP-LC and HP-LF meals than the STANDARD meal. Conclusion Altered processing of proinsulin and increased GLP-1 secretion in children with PWS after a high protein meal intake might enhance satiety and reduce energy intake.

Background Early-life malnutrition may have long-lasting effects on microbe-host interactions that affect health and disease susceptibility later in life. Diet quality and quantity in conjunction with toxin and pathogen exposure are key contributors to microbe-host physiology and malnutrition. Consequently, it is important to consider both diet- and microbe-induced pathologies as well as their interactions underlying malnutrition. Main Body Gastrointestinal immunity and digestive function are vital to maintain a symbiotic relationship between the host and microbiota. Childhood malnutrition can be impacted by numerous factors including gestational malnutrition, early life antibiotic use, psychological stress, food allergy, hygiene, and exposure to other chemicals and pollutants. These factors can contribute to reoccurring environmental enteropathy, a condition characterized by the expansion of commensal pathobionts and environmental pathogens. Reoccurring intestinal dysfunction, particularly during the critical window of development, may be a consequence of diet-microbe interactions and may lead to life-long immune and metabolic programming and increased disease risk. We provide an overview of the some key factors implicated in the progression of malnutrition (protein, fat, carbohydrate, iron, vitamin D, and vitamin B12) and discuss the microbiota during early life that may contribute health risk later in life. Conclusion Identifying key microbe-host interactions, particularly those associated with diet and malnutrition requires well-controlled dietary studies. Furthering our understanding of diet-microbe-host interactions will help to provide better strategies during gestation and early life to promote health later in life.

Background Anorexia nervosa (AN) is a serious mental disorder with a high mortality rate and often a chronic course. In contrast to many other common mental disorders, there is no drug therapy approved for AN. Methods We performed a narrative literature review to consider whether a choline-containing molecule, such as phosphatidylcholine (PC), with an omega (ω)-3 long chain polyunsaturated fatty acid (LCPUFA) could be a potential future medicinal treatment for AN. Results Choline and LCPUFAs have individually shown benefit for mental health. Case series and pilot studies suggest ω-3 LCPUFAs may be effective in eating disorders. However, pharmacodynamic and pharmacokinetic considerations suggest a greater benefit from the combination of both components. Conclusion The combination of a choline-containing molecule with an ω-3 LCPUFA may be clinically effective and well tolerated. This idea is supported by the current literature on the role of inflammation, the microbiome, the gut-brain-axis, hormonal, neurotransmitter and intracellular signalling, and on the structure and fluidity of nerve cells membranes in patients with AN.

Background Choline, an essential nutrient, is required for cell membranes, lipoprotein secretion, and methyl-group metabolism. Recently, it has been proposed that excess dietary choline consumption is metabolized to trimethylamine (TMA) by the gut microbiota; TMA is then oxidized to trimethylamine N-oxide (TMAO) in the liver. Epidemiological studies have clearly shown a positive correlation between plasma TMAO concentrations and cardiovascular events. Furthermore, some studies have shown an association between excess dietary choline, plasma TMAO concentrations, and atherosclerotic lesion size in apoE knockout (Apoe-/-) mice. Objective The aim of this study was to further investigate the relation between dietary choline and atherosclerosis in 2 atherogenic mouse models, the LDL receptor knockout (Ldlr-/-) and Apoe-/- mice. Methods Six feeding trials were performed in Ldlr-/- (40% high-fat diet) and Apoe-/- (unpurified diet) male mice, aged 8-10 wk. Mice randomly received control diet (0.1% choline), or choline- (1% choline), betaine- (0.1% choline and 0.9% betaine), or TMAO- (0.1% choline and 0.12% or 0.2% TMAO) supplemented diet for ≤28 wk. After the dietary intervention, the animals were killed and tissues and blood collected. Aortic atherosclerotic plaque area, plasma lipids, and choline metabolites were quantified. Results In Ldlr-/- mice, dietary supplementation for 8 wk with choline or TMAO increased plasma TMAO concentrations by 1.6- and 4-fold, respectively. After 16 wk, there was a 2-fold increase in plasma TMAO after dietary TMAO supplementation. In Apoe-/- mice, dietary supplementation with choline, betaine, or TMAO for 12 wk did not increase plasma TMAO concentrations. However, choline and TMAO supplementation for 28 wk significantly increased plasma TMAO concentrations by 1.8- and 1.5-fold, respectively. Contrary to predictions, atherosclerotic lesion size was not altered by any of the dietary interventions, irrespective of mouse model. Conclusions In our study, high intakes of dietary choline or TMAO supplementation did not influence atherosclerosis development in Ldlr-/- or Apoe-/- male mice.

BACKGROUND Maternal pre-postnatal psychosocial distress increases the risk for childhood allergic disease. This may occur through a host immunity pathway that involves intestinal secretory immunoglobulin A (sIgA). Experimental animal models show changes in the gut microbiome and immunity of offspring when exposed to direct or prenatal maternal stress, but little is known in humans. OBJECTIVE We determined the association between maternal depression and stress symptom trajectories and infant fecal sIgA concentrations. METHODS 1043 term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort were studied. Trajectories of maternal perceived stress and depression were based on scored scales administered in pregnancy and postpartum. sIgA was quantified in infant stool (mean age 3.7 months) with Immundiagnostik ELISA. Linear regression and logistic regression were employed to test associations. RESULTS Very low fecal sIgA concentrations were more common in infants of mothers in the antepartum and persistent depression trajectories (6% and 2% of women, respectively). Independent of breastfeeding status at fecal sampling, infant antibiotic exposure or other covariates, the antepartum depressive symptom trajectory was associated with reduced mean infant sIgA concentrations (β=-0.07, P

Background:Dietary long chain polyunsaturated fatty acids (LCPUFA) such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) play an important role in the development of the infant immune system. The role of LCPUFA in the T helper type 2 (Th2) biased immune system is unknown. We aimed to understand the effect of feeding LCPUFA during suckling and post-weaning on immune system development in Th2 bias Brown Norway rat offspring.Methods:Brown Norway dams were randomly assigned to nutritionally adequate maternal diet throughout the suckling period (0–3 weeks), namely, control diet (0% ARA, 0% DHA;n= 8) or ARA + DHA (0.45% ARA, 0.8% DHA;n= 10). At 3 weeks, offspring from each maternal diet group were randomized to either a control (0% ARA, 0% DHA;n= 19) or ARA+DHA post-weaning (0.5% ARA, 0.5% DHA;n= 18) diet. At 8 weeks, offspring were killed, and tissues were collected for immune cell function and fatty acid composition analyses.Results:ARA + DHA maternal diet resulted in higher (p< 0.05) DHA composition in breast milk (4×) without changing ARA levels. This resulted in more mature adaptive immune cells in spleen [T regulatory (Treg) cells and B cells], mesenteric lymph nodes (MLN, lower CD45RA+), and Peyer's patches (PP; higher IgG+, B cells) in the ARA+DHA group offspring at 8 weeks. ARA+DHA post-weaning diet (3–8 weeks) resulted in 2 × higher DHA in splenocyte phospholipids compared to control. This also resulted in higher Th1 cytokines, ~50% higher TNF-α and IFNγ, by PMAi stimulated splenocytesex vivo, with no differences in Th2 cytokines (IL-4, IL-13, and IL-10) compared to controls.Conclusion:Feeding dams a diet higher in DHA during the suckling period resulted in adaptive immune cell maturation in offspring at 8 weeks. Providing ARA and DHA during the post-weaning period in a Th2 biased Brown Norway offspring model may support Th1 biased immune response development, which could be associated with a lower risk of developing atopic diseases.

Depressive symptoms are common during pregnancy and are estimated to affect 7–20% of pregnant women, with higher prevalence found in those with a prior history of depression, in ethnic minorities, and those with increased exposure to stressful life events. Maternal depression often remains undiagnosed, and its symptoms can increase adverse health risks to the infant, including impaired cognitive development, behavioral problems, and higher susceptibility to physical illnesses. Accumulating research evidence supports the association between maternal physical health elements to infant gut health, including factors such as mode of delivery, medication, feeding status, and antibiotic use. However, specific maternal prenatal psychosocial factors and their effect on infant gut microbiota and immunity remains an area that is not well understood. This article reviews the literature and supplements it with new findings to show that prenatal depression alters: (i) gut microbial composition in partially and fully formula-fed infants at 3–4 months of age, and (ii) gut immunity (i.e., secretory Immunoglobulin A) in all infants independent of breastfeeding status. Understanding the implications of maternal depression on the infant gut microbiome is important to enhance both maternal and child health and to better inform disease outcomes and management.

Neonatal antibiotics administered to human infants initiate gut microbiota dysbiosis that may have long-term effects on body weight and metabolism. We examined antibiotic-induced adaptations in pancreatic islets of the piglet, a well-accepted model of human infant microbiota and pancreas development. Neonatal piglets randomized to amoxicillin [30 mg/kg body wt/day; n = 7, antibiotic (ANTI)] or placebo [vehicle control; n = 7, control (CON)] from postnatal day ( PND) 0– 13 were euthanized at PND7, 14, and 49. The metabolic phenotype along with functional, immunohistological, and transcriptional phenotypes of the pancreatic islets were studied. The gut microbiome was characterized by 16S rRNA gene sequencing, and microbial metabolites and microbiome-sensitive host molecules were measured. Compared with CON, ANTI PND7 piglets had elevated transcripts of genes involved in glucagon-like peptide 1 ((GLP-1) synthesis or signaling in islets ( P < 0.05) coinciding with higher plasma GLP-1 ( P = 0.11), along with increased tumor necrosis factor α ( Tnf) ( P < 0.05) and protegrin 1 ( Npg1) ( P < 0.05). Antibiotic-induced relative increases in Escherichia, Coprococcus, Ruminococcus, Dehalobacterium, and Oscillospira of the ileal microbiome at PND7 normalized after antibiotic withdrawal. In ANTI islets at PND14, the expression of key regulators pancreatic and duodenal homeobox 1 ( Pdx1), insulin-like growth factor-2 ( Igf2), and transcription factor 7-like 2 ( Tcf7l2) was downregulated, preceding a 40% reduction of β-cell area ( P < 0.01) and islet insulin content at PND49 ( P < 0.05). At PND49, a twofold elevated plasma insulin concentration ( P = 0.07) was observed in ANTI compared with CON. We conclude that antibiotic treatment of neonatal piglets elicited gut microbial changes accompanied by phasic alterations in key regulatory genes in pancreatic islets at PND7 and 14. By PND49, reduced β-cell area and islet insulin content were accompanied by elevated nonfasted insulin despite normoglycemia, indicative of islet stress.

BackgroundGenetic improvement for disease resilience is anticipated to be a practical method to improve efficiency and profitability of the pig industry, as resilient pigs maintain a relatively undepressed level of performance in the face of infection. However, multiple biological functions are known to be involved in disease resilience and this complexity means that the genetic architecture of disease resilience remains largely unknown. Here, we conducted genome-wide association studies (GWAS) of 465,910 autosomal SNPs for complete blood count (CBC) traits that are important in an animal’s disease response. The aim was to identify the genetic control of disease resilience.ResultsUnivariate and multivariate single-step GWAS were performed on 15 CBC traits measured from the blood samples of 2743 crossbred (Landrace × Yorkshire) barrows drawn at 2-weeks before, and at 2 and 6-weeks after exposure to a polymicrobial infectious challenge. Overall, at a genome-wise false discovery rate of 0.05, five genomic regions located onSus scrofachromosome (SSC) 2, SSC4, SSC9, SSC10, and SSC12, were significantly associated with white blood cell traits in response to the polymicrobial challenge, and nine genomic regions on multiple chromosomes (SSC1, SSC4, SSC5, SSC6, SSC8, SSC9, SSC11, SSC12, SSC17) were significantly associated with red blood cell and platelet traits collected before and after exposure to the challenge. By functional enrichment analyses using Ingenuity Pathway Analysis (IPA) and literature review of previous CBC studies, candidate genes located nearby significant single-nucleotide polymorphisms were found to be involved in immune response, hematopoiesis, red blood cell morphology, and platelet aggregation.ConclusionsThis study helps to improve our understanding of the genetic basis of CBC traits collected before and after exposure to a polymicrobial infectious challenge and provides a step forward to improve disease resilience.

The gut microbiome is hypothesized to play a crucial role in the development of obesity and insulin resistance (IR), the pathways linking the microbiome to IR in pediatrics have yet to be precisely characterized. We aimed to determine the relationship between the gut microbiome composition and metabolic functions and IR in children with obesity. In a cross-sectional study, fecal samples from children with obesity (10–16 years old) were collected for taxonomical and functional analysis of the fecal microbiome using shotgun metagenomics. The homeostatic model assessment for insulin resistance (HOMA-IR) was determined using fasting glucose and insulin. Associations between HOMA-IR and α-diversity measures as well as metabolic pathways were evaluated using Spearman correlations, relationships between HOMA-IR and β-diversity were assessed by permutational multivariate analysis of variance. Twenty-one children (nine males, median: age = 12.0 years, BMI z-score = 2.9, HOMA-IR = 3.6) completed the study. HOMA-IR was significantly associated with measures of α-diversity but not with β-diversity. Children with higher HOMA-IR exhibited lower overall species richness, Firmicutes species richness, and overall Proteobacteria species Shannon diversity. Furthermore, HOMA-IR was inversely correlated with the abundance of pathways related to the biosynthesis of lipopolysaccharides, amino acids, and short-chain fatty acids, whereas positive correlations between HOMA-IR and the peptidoglycan biosynthesis pathways were observed. In conclusion, insulin resistance was associated with decreased microbial α-diversity measures and abundance of genes related to the metabolic pathways. Our study provides a framework for understanding the microbial alterations in pediatric obesity.

OBJECTIVES: Industrialization has increased chronic disease prevalence, potentially due to lifestyle-induced disruptions of the gut microbiome. Decreased intake of dietary fibers is likely a key factor as they play an important role in chronic disease prevention and are growth substrates for the gut microbiota. Strategies that restore microbiome diversity, such as reintroducing health-promoting bacterial species and microbiota accessible carbohydrates (MACs), have been proposed to improve health but have not yet been systematically tested. The objective of this study was to determine the effects of a microbiome restoration strategy on metabolic markers in healthy adults. METHODS: Using a randomized controlled pilot study, 30 subjects consumed either a MAC-rich diet or their usual diet for three weeks each in a crossover fashion, with a three-week washout following each diet period. Participants were further divided into three groups and consumed either a single dose of one of two Limosilactobacillus reuteri strains, a rare species in industrialized microbiomes, or a placebo on day four of each diet period. Metabolic markers (standard lipid panel, glucose, insulin, C-reactive protein (CRP)) were assessed in blood collected at the start and end of each diet period. Data were analyzed using repeated measures ANOVA. RESULTS: Compared to baseline, the MAC-rich diet induced substantial metabolic changes, as it reduced total cholesterol (P

Skeletal muscle plays major roles in metabolism and overall health across the lifecycle. Emerging evidence indicates that prenatal (maternal diet during pregnancy and genetic defects) and postnatal factors (physical activity, hormones, dietary protein, and obesity) influence muscle mass acquisition and strength early in life. As a consequence, low muscle mass and strength contributes to several adverse health outcomes during childhood. Specifically, studies demonstrated inverse associations of muscle mass and strength to single and clustered metabolic risk factors. The literature also consistently reports that low muscle mass and strength are associated with reduced bone parameters during growth, increasing the risk of osteoporosis in old age. Furthermore, muscle mass gains are associated with improved neurodevelopment in the first years of life. Given these negative implications of low muscle mass and strength on health, it is crucial to track muscle mass and strength development from childhood to adolescence. Several body composition techniques are currently available for estimation of muscle mass, all with unique advantages and disadvantages. The value of ultrasound as a technique to measure muscle mass is emerging in pediatric research with potential for translating the research findings to clinical settings. For the assessment of muscle strength, the handgrip strength test has been widely employed but without a standardized protocol. Although further research is needed to define normative data and cut points for the low muscle mass and strength phenotype, the use of such non-invasive medical monitoring is a promising strategy to identify early abnormalities and prevent low muscle mass in adulthood.

The objective of this study was to investigate if DHA dietary supplementation enhances the anticancer actions of docetaxel (TXT) in two different drug resistant triple negative breast cancer (TNBC) patient-derived xenografts (PDX)s. In two experiments, female NSG mice bearing TNBC PDXs were randomized to one of two nutritionally adequate diets (20% w/w): control (0% DHA), or DHA (3.9% w/w of total fat) and injected with 0 or 5 mg/kg TXT, twice weekly for 6 weeks (n = 8 per group). Treatment response was determined by significant differences in tumor weight, and apoptotic, proliferation and cell cycle markers at endpoint. Mice bearing MAXF574 xenografts fed DHA diet and treated with TXT had a 57% reduction in tumor weight compared to mice fed control diet (P

Objectives Frailty can cause increased vulnerability to adverse health outcomes, such as falls, fractures, depression and reduced health-related quality of life (HRQoL). This cross-sectional study compared the differences in body composition, HRQoL, mental health and cognitive and vitamin D (vitD) status with health-care utilization by frail and nonfrail adults with diabetes mellitus (type 1 and type 2) and with chronic kidney disease (stages 1 through 5). Methods We studied adults with type 1 and type 2 diabetes and chronic kidney disease stages 1 through 5 who were participating in a longitudinal follow-up study (41 to 83 years of age; n=41). Body composition (dual-energy x-ray absorptiometry); vitD status (serum 25[OH]D3); frailty (Edmonton Frail Scale); depression (Major Depression Inventory); HRQoL (Short Form Health Survey-36); and cognitive status (Mini Mental State exam) were measured using validated tools. Participants who were on dialysis and had body weights >136 kg, and coinciding comorbidities known to influence vitD metabolism were excluded. Results Frailty occurred in 17% of participants (n=7). Frail participants had lower lean body mass, lower HRQoL scores (individual and composite scores), more depression (p= 0.05). Conclusions Frailty in an ambulatory population of adults with chronic kidney disease and diabetes is associated with low lean body mass, low HRQoL, greater depression and higher numbers of health-care visits.

Simple Summary There has been extensive research into the beneficial anticancer effects of n-3 long-chain polyunsaturated fatty acids (LCPUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in preclinical models of cancer. However, clinical evidence is limited. The aim of this scoping review was to summarize the current clinical evidence of n-3 LCPUFA supplementation in cancer treatment and highlight areas where more clinical evidence is needed. We summarized the results of 57 clinical trials with an EPA/DHA intervention and determined that supplementation could improve a variety of outcomes important to the patient and the disease process, including immune system modulation, improved weight maintenance and increased disease-free or progression-free survival. There is, however, a need for larger, well-controlled, statistically powered randomized controlled trials to move n-3 supplementation to clinical practice. Abstract This scoping review examines the evidence for n-3 long-chain polyunsaturated fatty acid [LCPUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] supplementation in clinical cancer therapy. A comprehensive literature search was performed to identify relevant clinical intervention studies conducted through August 2020. Fifty-seven unique cancer trials, assessing EPA and/or DHA supplementation pre- or post-treatment, concomitant with neoadjuvant chemotherapy, radiation or surgery, or in palliative therapy were included. Breast, head and neck, gastrointestinal, gastric, colorectal/rectal, esophageal, leukemia/lymphoma, lung, multiple myeloma and pancreatic cancers were investigated. Across the spectrum of cancers, the evidence suggests that supplementation increased or maintained body weight, increased progression-free and overall survival, improved overall quality of life, resulted in beneficial change in immune parameters and decreased serious adverse events. Taken together, the data support that EPA and/or DHA could be used to improve outcomes important to the patient and disease process. However, before incorporation into treatment can occur, there is a need for randomized clinical trials to determine the dose and type of n-3 LCPUFA intervention required, and expansion of outcomes assessed and improved reporting of outcomes.

Background: Epidemiological studies suggest that Bisphenol-A (BPA) is a developmental neurotoxicant, but the modifying effects of maternal nutrient status or neurotoxicant metal co-exposures have not been reported. Bisphenol-S (BPS) is being used as a BPA-alternative, but few epidemiological studies have evaluated its effects. Objectives: To examine if prenatal maternal BPA or BPS exposure are associated with children’s neurodevelopment at two years of age while adjusting for effect-measure modification by sex, maternal nutrients, and co-exposure to neurotoxic metals. Methods: Total BPA and BPS concentrations were analyzed in spot maternal urine from the second trimester; metals and maternal nutrient status were analyzed in blood. Child neurodevelopment was evaluated with the Bayley Scales of Infant Development-III (Bayley-III) at age 2 (394 maternal-child pairs) and linear regression was used to investigate associations. Results: Among nutrients and neurotoxic metals, selenium (Se) and cadmium (Cd) were the most significant predictors of Bayley-III scale scores. Higher maternal Cd was significantly correlated with poorer motor performance (p

Aims Maternal metabolic disorders place the mother at risk for negative pregnancy outcomes with potentially long‐term health impacts for the child. Metabolic syndrome, a cluster of features associated with increased risk of metabolic disorders, such as cardiovascular disease, diabetes and stroke, affects roughly one in five Canadians. Metabolomics is a relatively new technique that may be a useful tool to identify women at risk of metabolic disorders. This study set out to characterize urinary metabolic biomarkers of pregnant women with obesity and of pregnant women who later developed gestational diabetes mellitus (pre‐GDM), compared to controls. Methods and Materials Second trimester urine samples were collected through the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort and examined with 1H nuclear magnetic resonance (NMR) spectroscopy. Multivariate analysis was used to examine group differences, and machine learning feature selection tools identified the metabolites contributing to separation. Results Obesity and pre‐GDM metabolomes were distinct from controls and from each other. In each comparison, the glycine, serine and threonine pathways were the most impacted. Pantothenate, formic acid and glycine were downregulated by obesity, while formic acid, dimethylamine and galactose were downregulated in pre‐GDM. The three most impacted metabolites for the comparison of obesity versus pre‐GDM groups were upregulated creatine/caffeine, downregulated sarcosine/dimethylamine and upregulated maltose/sucrose in individuals who later developed GDM. Conclusion These findings suggest a role for urinary metabolomics in the prediction of GDM and metabolic marker identification for potential diagnostics and prognostics in women at risk., Urinary metabolomics can provide diagnostic signatures of obesity in pregnant mothers. The urine metabolome can predict the risk of gestational diabetes mellitus. Proton nuclear magnetic resonance spectroscopy is able to identify metabolic markers for diagnostics and prognostics in women at risk.

Dysbiosis of gut microbiota has been retrospectively linked to autism spectrum disorders but the temporal association between gut microbiota and early neurodevelopment in healthy infants is largely unknown. We undertook this study to determine associations between gut microbiota at two critical periods during infancy and neurodevelopment in a general population birth cohort. Here, we analyzed data from 405 infants (199 females) from the CHILD (Canadian Healthy Infant Longitudinal Development) Cohort Study. Neurodevelopmental outcomes were objectively assessed using the Bayley Scale of Infant Development (BSID-III) at 1 and 2 years of age. Microbiota profiling with 16S rRNA gene sequencing was conducted on fecal samples obtained at a mean age of 4 and 12 months. Using clustering methods, we identified three groups of infants based on relative abundance of gut microbiota at 12 months: Proteobacteria-dominant cluster (22.4% higher abundance at 12 months), Firmicutes-dominant cluster (46.0% higher abundance at 12 months) and Bacteroidetes-dominant cluster (31.6% higher abundance at 12 months). Relative to the Proteobacteria-dominant cluster, the Bacteroidetes-dominant cluster was associated with higher scores for cognitive (4.8 points; FDRp = .02), language (4.2 points; FDRp≤0.001), and motor (3.1 points; FDRp = .03) development at age 2 in models adjusted for covariates. When stratified by sex, only male infants with a Bacteroidetes-dominant microbiota had more favorable cognitive (5.9 points, FDRp = .06) and language (7.9 points; FDRp≤0.001) development. Genus Bacteroides abundance in gut microbiota was positively correlated with cognitive and language scores at age 2. Fully adjusted linear mixed model analysis revealed a positive association between Bacteroidetes-dominant cluster and change in cognitive and language performance from 1 to 2 years, predominantly among males. No associations were evident between 4-month microbiota clusters and BSID-II scores. Noteworthy is that enhanced sphingolipid synthesis and metabolism, and antagonism or competition between Bacteroides and Streptococcus were characteristic of a Bacteroidetes-dominant gut microbiota. This study found strong evidence of positive associations between Bacteroidetes gut microbiota in late infancy and subsequent neurodevelopment, most prominently among males but not females.

Human milk contains myriad bioactive lipids, many originating from the milk fat globule membrane. The mean ganglioside, cholesterol, and phospholipid concentrations range (per 100 mL) from 3.015.0 μg total lipid-bound sialic acid to 12.1–21.4 mg, to 16.0–36.0 mg, respectively. When measured, there are several other minor sterols found in milk. Sampling procedures, time postpartum, preterm birth, and analytical methodology all influence, to varying degrees, the estimated content of these lipids. Despite being in small and somewhat variable amounts in a mothers’ milk, these bioactive lipids likely contribute to the optimal development of her infant. The objective of this chapter is to review and summarize the published literature on what is known (and in many cases not known) about the content of these minor lipids in human milk across lactation and the methodologies used to quantify them.

Visual analogue scales (VAS) have commonly been used to assess appetite in children 8 years and older; however, these tools have been considered unreliable for children 7 years old and under. The objective of this pilot study was to develop a picture-based appetite assessment (PBAA) tool for children aged 4-10 years and pilot test it compared to a VAS-based appetite assessment. The study hypothesis was that the PBAA scores would decrease following the consumption of an ad libitum snack compared to the scores in the fasted state in children 4 to 10 years old; furthermore, there would be a good level of agreement (intraclass correlation coefficients0.75) between the appetite scores by the PBAA and VAS tools in children aged 8 years or older. At Visit 1, in a fasted state, all children (n = 15) completed the PBAA. Children who were 8-10 years old (n = 8) also completed the VAS-based appetite assessment. Then, an ad libitum snack was provided, and appetite assessments were repeated at 5-, 30- and 60-minutes post-snack. The same assessments were completed at visit 2 pre (fasting)- and post-consumption of a snack containing 25% of the amount consumed at visit 1 (limited snack). PBAA scores were different across time (P.001) and between types of meal (ad libitum vs limited snack) (P = .015) in all children. A good agreement between the PBAA and VAS scores at 30 and 60 minutes after both types of meal was found (intraclass correlation coefficients0.75). The PBAA tool was able to detect expected changes in appetite sensations and was in good agreement with the VAS instrument.

Despite recent advances in diagnosis and treatment, ovarian cancer (OC) is the most lethal gynecological malignancy and improving the efficacy of chemotherapy is of great interest. This study increases our understanding of how dietary intervention with docosahexaenoic acid (DHA)-a supplement proven safe for human consumption – enhances the anti-cancer effects of conventional chemotherapy. Our results demonstrated synergistic cell killing by DHA and carboplatin in OC cell lines. Furthermore, DHA supplementation alone and in combination with carboplatin significantly reduced OC growth in a high-grade serous OC patient-derived xenograft mouse model. Carboplatin administered intraperitoneally significantly reduced tumor growth in DHA-fed mice compared to mice on the control diet. Intravenous carboplatin administration in combination with DHA reduced tumor growth similarly to carboplatin or DHA monotherapies. The DHA-induced reduction in tumor growth in this model was associated with increased tumor necrosis and improved survival. As such, our findings provide a strong rationale to move to clinical trials that will determine whether DHA supplementation enhances the efficacy and tolerance of cytotoxic chemotherapy in patients with OC.

OBJECTIVES: Choline is a critical nutrient for fetal development. Pregnancy studies showed that most women have choline intakes below the adequate intake (AI) level of 450 mg/d. Research on plasma free choline as an indicator of dietary choline intake showed conflicting results to date. We sought to compare plasma free choline concentration between women with different choline intakes and to explore the association between plasma free choline and dietary choline intake in early (EP) and late pregnancy (LP). METHODS: This study included data and non-fasting plasma samples from pregnant women enrolled in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study. EP (20 weeks of gestation) dietary choline intake was estimated using a 24-hr recall. Two categories of dietary choline intake were created: 1) low choline (LCI), i.e., choline intake in 1st quartile (Q) in EP, with these women having choline intake in 1st or 2nd Q in LP (n = 61); 2) high choline intake (HCI), i.e., choline intake in 4th Q in EP and in 3rd or 4th Q in LP (n = 46). Linear mixed-effects models were used to explore the association between plasma free choline and dietary choline intake across EP and LP, after adjustment for maternal age, ethnicity and weeks of gestation. RESULTS: Median (IQR) maternal age was 32 (30–35) y, and 80% were Caucasian. LCI was 101 (86–109) and 109 (93–127) mg/day in EP and LP, respectively, and HCI was 251 (223–286) and 212 (177–274) mg/day. Plasma free choline (μmol/L) did not differ between LCI and HCI at EP [LCI: 10.6 (9.03, 12.9); HCI: 11.7 (10.2, 13.8)] and LP [LCI: 11.7 (10.6, 12.7); HCI: 12.7 (10.7, 15.8)] (P > 0.05, Wilcoxon rank-sum test). Per 10 mg of choline intake, plasma free choline increased by 0.34 (95%CI 0.12, 0.56) in those with LCI, and 0.18 (95%CI 0.050, 0.31) in women with HCI, across EP and LP after adjustment. CONCLUSIONS: In this subgroup of pregnant women, plasma free choline concentration did not reflect differences in dietary choline intake in EP or LP. This may be explained by an overall low choline intake (

OBJECTIVES: It is estimated that lifestyle factors, such as dietary intake, contribute up to 21% of all breast cancer (BC) cases. High dietary intakes of omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA) have been associated with a reduced incidence of BC. Dietary intake of n-3 LCPUFA typically correlate with blood fatty acid concentrations, but the relationship between blood fatty acid concentrations and BC risk has not yet been established. We hypothesized that higher plasma phospholipid (PL) content of n-3 LCPUFAs would be associated with a reduced risk of BC. METHODS: Plasma samples and relevant covariables were obtained from 614 age-matched women (203 with BC/411 control) from a nested case-control within Alberta's Tomorrow Project. PL fatty acid concentration and relative % composition were determined from baseline plasma samples (collected 9–16 years pre-BC diagnosis). Principal component analysis was employed to determine predictive models for fatty acid clusters. Conditional logistic regression models controlled for covariates were used to assess the relative risk of BC (odds ratio-OR) by fatty acid content. Sub-group analyses by menopausal status and BMI at baseline were also performed. RESULTS: When adjusted for BMI and menopausal status, individual fatty acids, including linoleic acid (OR = 1.75, 95% confidence interval (CI) = 1.08,2.84, P

In early childhood, individuals with Prader-Willi syndrome (PWS) experience excess weight gain and severe hyperphagia with food compulsivity, which often leads to early onset morbid obesity. Effective treatments for appetite suppression and weight control are currently unavailable for PWS. Our aim to further understand the pathogenesis of PWS led us to carry out a comprehensive search of the current and emerging therapies for managing hyperphagia and extreme weight gain in PWS. A literature search was performed using PubMed and the following keywords: "PWS" AND "therapy" OR "[drug name]"; reference lists, pharmaceutical websites, and the ClinicalTrials.gov registry were also reviewed. Articles presenting data from current standard treatments in PWS and also clinical trials of pharmacological agents in the pipeline were selected. Current standard treatments include dietary restriction/modifications, exercise, and growth hormone replacement, which appear to have limited efficacy for appetite and weight control in patients with PWS. The long-term safety and effectiveness of bariatric surgery in PWS remains unknown. However, many promising pharmacotherapies are in development and, if approved, will bring much needed choices into the PWS pharmacological armamentarium. With the progress that is currently being made in our understanding of PWS, an effective treatment may not be far off.

Background & Aims Few studies, even those with cohort designs, test the mediating effects of infant gut microbes and metabolites on the onset of disease. We undertook such a study. Methods: Using structural equation modeling path analysis, we tested directional relationships between first pregnancy, birth mode, prolonged labor and breastfeeding; infant gut microbiota, metabolites, and IgA; and childhood body mass index and atopy in 1667 infants. Results After both cesarean birth and prolonged labor with a first pregnancy, a higher Enterobacteriaceae/Bacteroidaceae ratio at 3 months was the dominant path to overweight; higher Enterobacteriaceae/Bacteroidaceae ratios and Clostridioides difficile colonization at 12 months were the main pathway to atopic sensitization. Depletion of Bifidobacterium after prolonged labor was a secondary pathway to overweight. Influenced by C difficile colonization at 3 months, metabolites propionate and formate were secondary pathways to child outcomes, with a key finding that formate was at the intersection of several paths. Conclusions Pathways from cesarean section and first pregnancy to child overweight and atopy share many common mediators of the infant gut microbiome, notably C difficile colonization.

Disease resilience is a valuable trait to help manage infectious diseases in livestock. It is anticipated that improved disease resilience will sustainably increase production efficiency, as resilient animals maintain their performance in the face of infection. The objective of this study was to identify phenotypes related to disease resilience using complete blood count (CBC) data from a wean-to-finish natural disease challenge model, established to mimic the disease pressure caused by many common pathogens at the commercial level of pig production. In total, 2433 F1 crossbred (Landrace × Yorkshire) barrows that went through the natural disease challenge model were classified into four groups (resilient, average, susceptible, and dead) based on their divergent responses in terms of growth and individual treatment. Three sets of blood samples for CBC analysis were drawn at 2-weeks before, and at 2- and 6-weeks after the challenge: Blood 1, Blood 3, and Blood 4 respectively. CBC of Blood 1 taken from healthy pigs before challenge did not show differences between groups. However, resilient animals were found to be primed to initiate a faster adaptive immune response and recover earlier following infection, with greater increases of lymphocyte concentration from Blood 1 to Blood 3 and for hemoglobin concentration and hematocrit from Blood 3 to Blood 4, but a lower neutrophil concentration from Blood 3 to Blood 4 than in susceptible and dead animals (FDR < 0.05). The CBC traits in response to the challenge were found to be heritable and genetically correlated with growth and treatment, which may indicate the potential for developing CBC under disease or commercial conditions as a phenotype in commercial systems as part of developing predictions for disease resilience.

Dietary management is important to prevent severe obesity in individuals with Prader-Willi syndrome (PWS); however, few studies have examined dietary intake and quality in youth with PWS. Our objective was to estimate intake of essential nutrients and diet quality in youth with PWS compared to those without PWS. Three-day food records were used to estimate intake of energy, nutrients, nutrient-density, foods, and adherence to healthy eating guidelines. Data were presented as medians and interquartile ranges with Mann-Whitney U and Fisher's test used to compare between groups with p < .05 considered significant. Youth with (n = 23) and without (n = 23) PWS were similar in age and sex distribution. The PWS group had a lower energy intake (p ≤ .001), higher nutrient density (p = .003), and better adherence to guidelines (p = .007) compared to the control group. The proportion with nutrient intake from food below Estimated Average Requirement or Adequate Intake were similar between groups. Fiber, vitamin D, calcium, and potassium intake were below recommendations in 50% or more in both groups. The inclusion of supplement intake lowered the proportion below recommendations, except for fiber and potassium. Youth with PWS had a similar nutrient intake as those without PWS despite a lower energy intake, which could be attributed to higher diet quality. However, more than half of youth with PWS were at risk of inadequate fiber, vitamin D, calcium, and potassium intake. A greater emphasis on nutrient-dense foods would improve nutrient intake, but supplements may be warranted in youth with PWS who do not meet recommendations.

Colonization with Clostridioides difficile occurs in up to half of infants under the age of 3 months, is strongly influenced by feeding modality and is largely asymptomatic. In spite of this, C. difficile's presence has been associated with susceptibility to chronic disease later in childhood, perhaps by promoting or benefiting from changes in infant gut microbiome development, including colonization with pathogenic bacteria and disrupted production of microbial bioactive metabolites and proteins. In this study, the microbiomes of 1554 infants from the CHILD Cohort Study were described according to C. difficile colonization status and feeding mode at 3–4 months of age. C. difficile colonization was associated with a different gut microbiome profile in exclusively breastfed (EBF) vs. exclusively formula fed (EFF) infants. EBF infants colonized with C. difficile had an increased relative abundance of Firmicutes and Proteobacteria, decreased relative abundance of Bifidobacteriaceae, greater microbiota alpha-diversity, greater detectable fecal short chain fatty acids (SCFA), and lower detectable fecal secretory Immunoglobulin A (sIgA) than those not colonized. Similar but less pronounced differences were seen among partially breastfed infants (PBF) but EFF infants did not possess these differences in the gut microbiome according to colonization status. Thus, breastfed infants colonized with C. difficile appear to possess a gut microbiome that differs from non-colonized infants and resembles that of EFF infants, but the driving force and direction of this association remains unknown. Understanding these compositional differences as drivers of C. difficile colonization may be important to ensure future childhood health.

Objective Multiple studies have explored the association between serum or plasma vitamin B12 status and obesity, in part because of the relationship between elevated homocysteine concentrations and atherosclerosis. This review will address the inconsistent finding of these studies with the objective of determining whether vitamin B12 concentrations are lower in people with higher body mass indices. Design MEDLINE and EMBASE were searched to February 2017. Observational studies in general and clinical populations comparing serum/plasma B12 concentrations across groups of different body mass indices were selected. We did network and pairwise meta-analyses of serum/plasma B12, folate and homocysteine using frequentist techniques. Evidence-based items potentially indicating risk of bias were assessed. Results Of 844 citations, we identified 19 eligible observational studies with 7,055 participants. The overall network, while showing no significant inconsistency between indirect and direct comparisons (P = 0.34), was qualitatively inconsistent. Based on the results of the meta-regression, in an exploratory sub-network meta-analysis where obesity groups were combined, we excluded disease-specific populations and studies with inadequate description of populations. The direction of the indirect and direct evidence was consistent. The pairwise results from this sub-network showed lower levels of B12 in people with higher body mass indices: obesity versus control difference in means (MD) -56 pmol L-1 (95% CI -90, -23), obesity versus overweight MD -21 pmol L-1 (95% CI -37, -5) and overweight versus control MD -51 pmol L-1 (95% CI -51, -24). Heterogeneity remained very large for most comparisons, and all the studies carried a high risk for bias. Conclusions This review did not establish an inverse association (or J-curve) between serum or plasma B12 concentrations and body mass index, but the direct pairwise evidence is consistent with an inverse association and supports further investigation.

Spent hens have low market value and incur significant costs for disposal. This study explored the use of spent hens as a source of bioactive peptides. Spent hen hydrolysates prepared by Protease M or Protex 50FP exhibited interleukin (IL)-6 inhibitory activity in endotoxin-activated macrophage-like U937 cells (p .05). The potential peptides from Protex 50FP hydrolysate were further fractionated using a combination of ultrafiltration, solid-phase extraction and high-performance liquid chromatography; 17 novel peptides encoded in major muscle proteins were identified by mass spectrometry analysis, of which 7 were chemically synthesized and assayed for the IL-6 inhibitory activity. At a concentration of 100 µg/mL, peptide FLWGKSY induced a 79% reduction of IL-6 production in endotoxin-activated macrophage-like U937 cells, which is comparable to results reported from other food sources. Our results indicate that spent hens have potential to be a source of bioactive peptides for anti-inflammatory applications.

BACKGROUND A dietary supply of docosahexaenoic acid (DHA) and arachidonic acid (AA) is critical for neonatal retinal development. Both are absent/minimal in parenteral nutrition (PN) using soy-oil emulsions ([SO] Intralipid®) traditionally used for neonatal intestinal failure. In contrast, fish-oil emulsions ([FO] Omegaven®) are enriched in DHA/AA. The aim of this study was to compare retinal function and fatty acid content in neonatal piglets fed PN with SO or FO. METHODS Two-5-day-old piglets were randomly allocated to SO (n = 4) or FO (n = 4), provided at equivalent doses (5g/kg/d). After 14 days of PN, retinal function was assessed by electroretinography and retinas were harvested for fatty acid content analysis. Sow-fed piglets served as a reference (REF). RESULTS Light flash-elicited stoppage of cone and rod dark-currents (a-waves) and the ensuing postsynaptic activation of cone and rod ON bipolar cells (b-waves) were comparable between SO and REF. Responses recorded from FO were subnormal (P

Dietary proteins harbour bioactive peptides that exert various physiological activities. Chicken meat prepared from spent layers from the egg industry is an inexpensive source of protein for the production of bioactive peptides. This study explored the effect of hen muscle-derived peptides prepared by enzymatic hydrolysis on immune functions. The hydrolysate was incorporated into the diet of weanling Sprague-Dawley rats (n = 8 per diet) for 3 weeks at 2% or 5% addition (w/w diet). At a dose of 5% (w/w) the hydrolysate exhibited immunomodulatory effects on splenocytes, including a lower proportion of OX6+ (professional antigen presenting cells) and a higher proportion of CD11b/c+ cells (macrophages/monocytes) (p < 0.05) compared to the isonitrogenous control diet. Meanwhile, the production of anti-inflammatory cytokine interleukin (IL)-10 by splenocytes stimulated ex vivo with mitogens was significantly higher from hydrolysate treatment; there was no significant difference in the other cytokines (IL-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-6 and IL-2) investigated. Supplementing with the hydrolysate did not alter the growth, food intake and organ weights in young rodents. These results indicated that the spent hen muscle protein hydrolysate has the potential to be developed for value-added products with anti-inflammatory properties.

Background Accelerated loss of adipose tissue in cancer is associated with shorter survival, and reduced quality of life. Evidence is emerging suggesting tumour association with alterations in adipose tissue, but much less is known about drug-related mechanisms contributing to adipose atrophy. Identification of mechanisms by which tumour and cancer treatments, such as chemotherapy, affect adipose tissue are required to develop appropriate therapeutic interventions to prevent fat depletion in cancer. This pre-clinical study aimed to assess alterations in adipose tissue during the clinical course of cancer. Methods Fischer 344 rats bearing the Ward colorectal tumour were euthanized before chemotherapy, after 1- cycle, or 2-cycles of a combination chemotherapy consisting of Irinotecan (CPT-11) combined with 5-fluorouracil (5-FU), which recapitulates first line treatment for human colorectal cancer. Periuterine adipose tissue was isolated. Healthy rats served as a reference group. Histological analysis (hematoxylin and eosin), Real-time PCR (TaqMan) and proteomic analysis (LC-MS/MS) were performed. Results Larger adipocytes (3993.7 ± 52.6 μm2) in tumour-bearing animals compared to the reference group (3227.7 ± 36.7 μm2; p

Adverse childhood experiences (ACEs) of a woman can lead to dysregulated hypothalamus-pituitary-adrenal (HPA) axis during pregnancy, which can in turn adversely affect her offspring HPA axis function. Choline and docosahexaenoic acid (DHA) are dietary factors with the potential to favorably modify the stress response system. The current study aimed to investigate whether maternal choline intake and DHA status moderate the effects of maternal ACEs exposure on maternal and infant HPA axes function. Participants were a sub-sample of the prospective longitudinal Alberta Pregnancy Outcomes and Nutrition (APrON) study consisting of 340 mothers and 238 infants. We collected data on maternal ACEs, maternal choline intake (24-hour dietary recall) and serum phospholipid DHA concentrations (at each trimester). Women self-collected saliva samples on two consecutive days (at waking, +30 min, 1100 h, and 2100 h) in each trimester to calculate the cortisol awakening response (CAR) and total daytime cortisol. Infants’ salivary cortisol was measured before and after (20, and 40 min) exposure to a blood draw stressor 3 months postpartum. During pregnancy, choline intake moderated (reduced) the association between maternal ACEs and CAR (β = −0.003; 95% CI −0.006, −0.003), but not total daytime cortisol. DHA status did not moderate the association between ACEs and CAR or total daytime cortisol. Choline intake also moderated (reduced) the association between maternal CAR and infant cortisol during a stress task (β = −0.0001; 95% CI −0.0002, −0.00003). Maternal DHA status revealed no modifying effects on these associations. Our findings suggest that maternal choline intake, but not DHA status, can buffer the associations between ACEs and maternal HPA axis, as well as maternal and infant HPA axes function.

Choline is an essential nutrient required for various biological processes. Eggs, dairy, and meat are rich in phosphatidylcholine (PC), whereas cereal and legumes are rich in free choline. Excess dietary choline leads to increase plasma trimethylamine N-oxide (TMAO). Epidemiological studies suggest that plasma TMAO is a biomarker for atherosclerosis and it has been suggested that a lower intake of eggs and meat would reduce choline consumption and thus reduce atherosclerosis development. To investigate whether the form of dietary choline influences atherosclerosis development in Ldlr-/-, we randomly fed Ldlr-/-male mice (aged 8 - 10 wk) one of the three 40% (calories) high fat diets (with 0.5% w/w of cholesterol): Control (0.1% w/w free-choline, CON), choline-supplemented (0.4% free-choline, CS), or PC-supplemented (0.1% free-choline and 0.3% choline from PC, PCS). After 12-wk of dietary intervention, the animals were euthanized and tissues and blood collected. Aortic atherosclerotic plaque area, plasma choline, lipid metabolites, and spleen and peripheral blood cell phenotypes were quantified. Surprisingly, the PCS group had significantly lower atherosclerotic lesions while having 2-fold higher plasma TMAO levels compared with both CON and CS groups (P