The effect of oral probiotics on response to vaccination in older adults: a systematic review of randomised controlled trials.

This systematic review evaluated the impact of oral probiotics on the immune response to vaccination in older people. A literature search was performed in three electronic databases up to January 2023. Randomised controlled trials (RCTs) conducted in older people (age ≥ 60 years) investigating oral probiotics and vaccine response outcomes were included. Characteristics and outcome data of the included studies were extracted and analysed and study quality was assessed using the Cochrane Risk of Bias Tool for randomised trials. Ten RCTs involving 1,560 participants, reported in 9 papers, were included. Nine studies involved the seasonal influenza vaccine and one a COVID-19 vaccine. All studies used lactobacilli, some in combination with bifidobacteria. Studies reported outcomes including anti-vaccine antibody titres or concentrations, seroconversion and seroprotection. When comparing antibody titres, seroprotection rate and seroconversion rate between probiotic and placebo groups expressed as a response ratio, the weighted mean values were 1.29, 1.16 and 2.00, respectively. Meta-analysis showed that probiotics increase seroconversion rates to all three strains of the seasonal influenza vaccine: odds ratio (95% confidence interval) 2.74 (1.31, 5.70; P = 0.007) for the H1N1 strain; 1.90 (1.04, 3.44; P = 0.04) for the H3N2 strain; 1.72 (1.05, 2.80; P = 0.03) for the B strain. There was a low level of heterogeneity in these findings. Several studies were at high risk of bias due to missing outcome data. Lactobacilli may improve the vaccine response, but further research is needed to be more certain of this.

Synbiotics Alter Fecal Microbiomes, But Not Liver Fat or Fibrosis, in a Randomized Trial of Patients With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS: Dysbiosis of the intestinal microbiota has been associated with nonalcoholic fatty liver disease (NAFLD). We investigated whether administration of a synbiotic combination of probiotic and prebiotic agents affected liver fat content, biomarkers of liver fibrosis, and the composition of the fecal microbiome in patients with NAFLD. METHODS: We performed a double-blind phase 2 trial of 104 patients with NAFLD in the United Kingdom. Participants (mean age, 50.8 ± 12.6 years; 65% men; 37% with diabetes) were randomly assigned to groups given the synbiotic agents (fructo-oligosaccharides, 4 g twice per day, plus Bifidobacterium animalis subspecies lactis BB-12; n = 55) or placebo (n = 49) for 10-14 months. Liver fat content was measured at the start and end of the study by magnetic resonance spectroscopy, and liver fibrosis was determined from a validated biomarker scoring system and vibration-controlled transient elastography. Fecal samples were collected at the start and end of the study, the fecal microbiome were analyzed by 16S ribosomal DNA sequencing. RESULTS: Mean baseline and end-of-study magnetic resonance spectroscopy liver fat percentage values were 32.3% ± 24.8% and 28.5% ± 20.1% in the synbiotic group and 31.3% ± 22% and 25.2% ± 17.2% in the placebo group. In the unadjusted intention-to-treat analysis, we found no significant difference in liver fat reduction between groups (ß = 2.8; 95% confidence interval, -2.2 to 7.8; P = .30). In a fully adjusted regression model (adjusted for baseline measurement of the outcome plus age, sex, weight difference, and baseline weight), only weight loss was associated with a significant decrease in liver fat (ß = 2; 95% confidence interval, 1.5-2.6; P = .03). Fecal samples from patients who received the synbiotic had higher proportions of Bifidobacterium and Faecalibacterium species, and reductions in Oscillibacter and Alistipes species, compared with baseline; these changes were not observed in the placebo group. Changes in the composition of fecal microbiota were not associated with liver fat or markers of fibrosis. CONCLUSIONS: In a randomized trial of patients with NAFLD, 1 year of administration of a synbiotic combination (probiotic and prebiotic) altered the fecal microbiome but did not reduce liver fat content or markers of liver fibrosis. (ClinicalTrials.gov, Number: NCT01680640).

Dysregulation of endocannabinoid concentrations in human subcutaneous adipose tissue in obesity and modulation by omega-3 polyunsaturated fatty acids.

Obesity is believed to be associated with a dysregulated endocannabinoid system which may reflect enhanced inflammation. However, reports of this in human white adipose tissue (WAT) are limited and inconclusive. Marine long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and therefore may improve obesity-associated adipose tissue inflammation. Therefore, fatty acid (FA) concentrations, endocannabinoid concentrations, and gene expression were assessed in subcutaneous WAT (scWAT) biopsies from healthy normal weight individuals (BMI 18.5-25 kg/m2) and individuals living with metabolically healthy obesity (BMI 30-40 kg/m2) prior to and following a 12-week intervention with 3 g fish oil/day (1.1 g eicosapentaenoic acid (EPA) + 0.8 g DHA) or 3 g corn oil/day (placebo). WAT from individuals living with metabolically healthy obesity had higher n-6 PUFAs and EPA, higher concentrations of two endocannabinoids (anandamide (AEA) and eicosapentaenoyl ethanolamide (EPEA)), higher expression of phospholipase A2 Group IID (PLA2G2D) and phospholipase A2 Group IVA (PLA2G4A), and lower expression of CNR1. In response to fish oil intervention, WAT EPA increased to a similar extent in both BMI groups, and WAT DHA increased by a greater extent in normal weight individuals. WAT EPEA and docosahexaenoyl ethanolamide (DHEA) increased in normal weight individuals only and WAT 2-arachidonyl glycerol (2-AG) decreased in individuals living with metabolically healthy obesity only. Altered WAT fatty acid, endocannabinoid, and gene expression profiles in metabolically healthy obesity at baseline may be linked. WAT incorporates n-3 PUFAs when their intake is increased which affects the endocannabinoid system; however, effects appear greater in normal weight individuals than in those living with metabolically healthy obesity.

Differential SLC6A4 methylation: a predictive epigenetic marker of adiposity from birth to adulthood.

BACKGROUND: The early life environment may influence susceptibility to obesity and metabolic disease in later life through epigenetic processes. SLC6A4 is an important mediator of serotonin bioavailability, and has a key role in energy balance. We tested the hypothesis that methylation of the SLC6A4 gene predicts adiposity across the life course. METHODS: DNA methylation at 5 CpGs within the SLC6A4 gene identified from a previous methyl binding domain array was measured by pyrosequencing. We measured DNA methylation in umbilical cord (UC) from children in the Southampton Women's Survey cohort (n = 680), in peripheral blood from adolescents in the Western Australian Pregnancy Cohort Study (n = 812), and in adipose tissue from lean and obese adults from the UK BIOCLAIMS cohort (n = 81). Real-time PCR was performed to assess whether there were corresponding alterations in gene expression in the adipose tissue. RESULTS: Lower UC methylation of CpG5 was associated with higher total fat mass at 4 years (p = 0.031), total fat mass at 6-7 years (p = 0.0001) and % fat mass at 6-7 years (p = 0.004). Lower UC methylation of CpG5 was also associated with higher triceps skinfold thickness at birth (p = 0.013), 6 months (p = 0.038), 12 months (p = 0.062), 2 years (p = 0.0003), 3 years (p = 0.00004) and 6-7 years (p = 0.013). Higher maternal pregnancy weight gain (p = 0.046) and lower parity (p = 0.029) were both associated with lower SLC6A4 CpG5 methylation. In adolescents, lower methylation of CpG5 in peripheral blood was associated with greater concurrent measures of adiposity including BMI (p ≤ 0.001), waist circumference (p = 0.011), subcutaneous fat (p ≤ 0.001) and subscapular, abdominal and suprailiac skinfold thicknesses (p = 0.002, p = 0.008, p = 0.004, respectively). In adipose tissue, methylation of both SLC6A4 CpG5 (p = 0.019) and expression of SLC6A4 (p = 0.008) was lower in obese compared with lean adults. CONCLUSIONS: These data suggest that altered methylation of CpG loci within SLC6A4 may provide a robust marker of adiposity across the life course.

Omega-3 fatty acid supplementation influences the whole blood transcriptome in women with obesity, associated with pro-resolving lipid mediator production.

The n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may reduce low-grade inflammation associated with obesity. The relationship between therapeutic response to n-3 PUFAs and modification of the transcriptome in obesity or metabolic syndrome remains to be explored. Blood samples were obtained from women with obesity before and after three-months supplementation with a moderate dose of n-3 PUFAs (1.8g EPA+DHA per day) or from controls. n-3 PUFAs (GC) and plasma concentrations of lipoxins, resolvins, protectin X (GC-MS/MS) and inflammatory markers (ELISA) were measured. Whole blood transcriptome was assayed using microarray. Women supplemented with n-3 PUFAs for 3months had significantly higher levels of EPA and DHA in plasma phosphatidylcholine. n-3 PUFA supplementation, in contrast to placebo, significantly decreased the concentrations of several inflammatory markers (SELE, MCP-1, sVCAM-1, sPECAM-1, and hsCRP), fasting triglycerides and insulin and increased the concentrations of pro-resolving DHA derivatives in plasma. The microarray data demonstrated effects of n-3 PUFAs on PPAR-α, NRF2 and NF-κB target genes. N-3 PUFAs increased DHA-derived pro-resolving mediators in women with obesity. Elevated resolvins and up-regulation of the resolvin receptor occurred in parallel with activation of PPAR-α target genes related to lipid metabolism and of NRF2 up-regulated antioxidant enzymes.

Effect of a synbiotic on the response to seasonal influenza vaccination is strongly influenced by degree of immunosenescence.

BACKGROUND: Ageing increases risk of respiratory infections and impairs the response to influenza vaccination. Pre- and probiotics offer an opportunity to modulate anti-viral defenses and the response to vaccination via alteration of the gut microbiota. This study investigated the effect of a novel probiotic, Bifidobacterium longum bv. infantis CCUG 52,486, combined with a prebiotic, gluco-oligosaccharide (B. longum + Gl-OS), on the response to seasonal influenza vaccination in young and older subjects in a double-blind, randomized controlled trial, taking into account the influence of immunosenescence markers at baseline. RESULTS: Vaccination resulted in a significant increase in total antibody titres, vaccine-specific IgA, IgM and IgG and seroprotection to all three subunits of the vaccine in both young and older subjects, and in general, the increases in young subjects were greater. There was little effect of the synbiotic, although it tended to reduce seroconversion to the Brisbane subunit of the vaccine and the vaccine-specific IgG response in older subjects. Immunological characterization revealed that older subjects randomized to the synbiotic had a significantly higher number of senescent (CD28(-)CD57(+)) helper T cells at baseline compared with those randomized to the placebo, and they also had significantly higher plasma levels of anti-CMV IgG and a greater tendency for CMV seropositivity. Moreover, higher numbers of CD28(-)CD57(+) helper T cells were associated with failure to seroconvert to Brisbane, strongly suggesting that the subjects randomized to the synbiotic were already at a significant disadvantage in terms of likely ability to respond to the vaccine compared with those randomized to the placebo. CONCLUSIONS: Ageing was associated with marked impairment of the antibody response to influenza vaccination in older subjects and the synbiotic failed to reverse this impairment. However, the older subjects randomized to the synbiotic were at a significant disadvantage due to a greater degree of immunosenscence at baseline compared with those randomized to the placebo. Thus, baseline differences in immunosenescence between the randomized groups are likely to have influenced the outcome of the intervention, highlighting the need for detailed immunological characterization of subjects prior to interventions. TRIAL REGISTRATION: Clinicaltrials.gov NCT01066377.

No Effect of Omega-3 Fatty Acid Supplementation on Cognition and Mood in Individuals with Cognitive Impairment and Probable Alzheimer's Disease: A Randomised Controlled Trial.

Findings from epidemiological and observational studies have indicated that diets high in omega-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may reduce the risk of cognitive decline and Alzheimer's disease (AD). To determine if increasing intake of DHA and EPA through supplementation is beneficial to cognition and mood in individuals with cognitive impairment no dementia (CIND) or Alzheimer's disease (AD) a four month, randomised, double-blind, placebo controlled study was conducted. Fifty-seven participants with CIND and nineteen with AD were randomised to receive either omega-3 PUFAs (600 mg EPA and 625 mg DHA per day) or placebo (olive oil) over a four month period. Elevating depleted levels of EPA and DHA through supplementation in individuals with CIND or AD was found to have negligible beneficial effect on their cognition or mood. These findings confirm an overall negligible benefit of omega-3 PUFA supplementation for those with cognitive impairment and dementia. More intervention studies need to be undertaken with longer study durations and larger sample sizes. It may prove fruitful to examine effects of different doses as well as effects in other dementia subtypes.

Xylo-oligosaccharides alone or in synbiotic combination with Bifidobacterium animalis subsp. lactis induce bifidogenesis and modulate markers of immune function in healthy adults: a double-blind, placebo-controlled, randomised, factorial cross-over study.

Prebiotics, probiotics and synbiotics are dietary ingredients with the potential to influence health and mucosal and systemic immune function by altering the composition of the gut microbiota. In the present study, a candidate prebiotic (xylo-oligosaccharide, XOS, 8 g/d), probiotic (Bifidobacterium animalis subsp. lactis Bi-07, 109 colony-forming units (CFU)/d) or synbiotic (8 g XOS+109 CFU Bi-07/d) was given to healthy adults (25-65 years) for 21 d. The aim was to identify the effect of the supplements on bowel habits, self-reported mood, composition of the gut microbiota, blood lipid concentrations and immune function. XOS supplementation increased mean bowel movements per d (P= 0·009), but did not alter the symptoms of bloating, abdominal pain or flatulence or the incidence of any reported adverse events compared with maltodextrin supplementation. XOS supplementation significantly increased participant-reported vitality (P= 0·003) and happiness (P= 0·034). Lowest reported use of analgesics was observed during the XOS+Bi-07 supplementation period (P= 0·004). XOS supplementation significantly increased faecal bifidobacterial counts (P= 0·008) and fasting plasma HDL concentrations (P= 0·005). Bi-07 supplementation significantly increased faecal B. lactis content (P= 0·007), lowered lipopolysaccharide-stimulated IL-4 secretion in whole-blood cultures (P= 0·035) and salivary IgA content (P= 0·040) and increased IL-6 secretion (P= 0·009). XOS supplementation resulted in lower expression of CD16/56 on natural killer T cells (P= 0·027) and lower IL-10 secretion (P= 0·049), while XOS and Bi-07 supplementation reduced the expression of CD19 on B cells (XOS × Bi-07, P= 0·009). The present study demonstrates that XOS induce bifidogenesis, improve aspects of the plasma lipid profile and modulate the markers of immune function in healthy adults. The provision of XOS+Bi-07 as a synbiotic may confer further benefits due to the discrete effects of Bi-07 on the gut microbiota and markers of immune function.

Increased dietary α-linolenic acid has sex-specific effects upon eicosapentaenoic acid status in humans: re-examination of data from a randomised, placebo-controlled, parallel study.

BACKGROUND: There is a metabolic pathway by which mammals can convert the omega-3 (n-3) essential fatty acid α-linolenic acid (ALA) into longer-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). As far as we know there are currently no studies that have specifically examined sex differences in the LC n-3 PUFA response to increased dietary ALA intake in humans, although acute studies with isotope-labelled ALA identified that women have a significantly greater capacity to synthesise EPA and DHA from ALA compared to men. FINDINGS: Available data from a placebo-controlled, randomised study were re-examined to identify whether there are sex differences in the LC n-3 PUFA response to increased dietary ALA intake in humans. There was a significant difference between sexes in the response to increased dietary ALA, with women having a significantly greater increase in the EPA content of plasma phospholipids (mean +2.0% of total fatty acids) after six months of an ALA-rich diet compared to men (mean +0.7%, P = 0.039). Age and BMI were identified as predictors of response to dietary ALA among women. CONCLUSIONS: Women show a greater increase in circulating EPA than men during increased dietary ALA consumption. Further understanding of individual variation in the response to dietary ALA could inform nutrition advice, with recommendations being specifically tailored according to habitual diet, sex, age and BMI.

Membrane lipid composition of bronchial epithelial cells influences antiviral responses during rhinovirus infection.

Lipids and their mediators have important regulatory functions in many cellular processes, including the innate antiviral response. The aim of this study was to compare the lipid membrane composition of in vitro differentiated primary bronchial epithelial cells (PBECs) with ex vivo bronchial brushings and to establish whether any changes in the lipid membrane composition affect antiviral defense of cells from donors without and with severe asthma. Using mass spectrometry, we showed that the lipid membrane of in vitro differentiated PBECs was deprived of polyunsaturated fatty acids (PUFAs) compared to ex vivo bronchial brushings. Supplementation of the culture medium with arachidonic acid (AA) increased the PUFA-content to more closely match the ex vivo membrane profile. Rhinovirus (RV16) infection of AA-supplemented cultures from healthy donors resulted in significantly reduced viral replication while release of inflammatory mediators and prostaglandin E2 (PGE2) was significantly increased. Indomethacin, an inhibitor of prostaglandin-endoperoxide synthases, suppressed RV16-induced PGE2 release and significantly reduced CXCL-8/IL-8 release from AA-supplemented cultures indicating a link between PGE2 and CXCL8/IL-8 release. In contrast, in AA-supplemented cultures from severe asthmatic donors, viral replication was enhanced whereas PTGS2 expression and PGE2 release were unchanged and CXCL8/IL-8 was significantly reduced in response to RV16 infection. While the PTGS2/COX-2 pathway is initially pro-inflammatory, its downstream products can promote symptom resolution. Thus, reduced PGE2 release during an RV-induced severe asthma exacerbation may lead to prolonged symptoms and slower recovery. Our data highlight the importance of reflecting the in vivo lipid profile in in vitro cell cultures for mechanistic studies.

Lower omega-3 fatty acid intake and status are associated with poorer cognitive function in older age: A comparison of individuals with and without cognitive impairment and Alzheimer's disease.

OBJECTIVES: Various strands of evidence suggest that low intake of omega-3 fatty acids increases risk of cognitive decline and dementia. The present study investigated differences in dietary intake and blood plasma content of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) in individuals with cognitive impairment no dementia (CIND), individuals with Alzheimer's disease (AD), and healthy volunteers (HV). METHODS: A total of 135 individuals aged between 55 and 91 years (19 AD, 55 CIND, and 61 HV) were assessed predominantly within a hospital setting. RESULTS: Compared with age and sex-matched HV, individuals with AD or CIND performed poorly on a majority of tests of cognitive function. Impairment was greatest for delayed and verbal recognition memory. CIND individuals were less impaired than AD individuals. Omega-3 intake and the percentage of EPA and DHA in plasma phosphatidylcholine (PC) showed a similar pattern (AD < HV, with intermediate scores for CIND). Across the whole sample, and after controlling for age, years of education, level of socio-economic deprivation, and gender, omega-3 intake, plasma PC DHA, and plasma PC EPA were all significant positive predictors of memory functioning. DISCUSSION: These results are consistent with the possibility that omega-3 fatty acid nutrition has an impact on cognitive decline, but could equally be explained by dietary changes that occurred after onset of cognitive decline. It is also possible that the results could be explained by unknown confounding factors.

Potential Biomarkers, Risk Factors, and Their Associations with IgE-Mediated Food Allergy in Early Life: A Narrative Review.

Food allergy (FA) affects the quality of life of millions of people worldwide and presents a significant psychological and financial burden for both national and international public health. In the past few decades, the prevalence of allergic disease has been on the rise worldwide. Identified risk factors for FA include family history, mode of delivery, variations in infant feeding practices, prior diagnosis of other atopic diseases such as eczema, and social economic status. Identifying reliable biomarkers that predict the risk of developing FA in early life would be valuable in both preventing morbidity and mortality and by making current interventions available at the earliest opportunity. There is also the potential to identify new therapeutic targets. This narrative review provides details on the genetic, epigenetic, dietary, and microbiome influences upon the development of FA and synthesizes the currently available data indicating potential biomarkers. Whereas there is a large body of research evidence available within each field of potential risk factors, there is a very limited number of studies that span multiple methodological fields, for example, including immunology, microbiome, genetic/epigenetic factors, and dietary assessment. We recommend that further collaborative research with detailed cohort phenotyping is required to identify biomarkers, and whether these vary between at-risk populations and the wider population. The low incidence of oral food challenge-confirmed FA in the general population, and the complexities of designing nutritional intervention studies will provide challenges for researchers to address in generating high-quality, reliable, and reproducible research findings.

Modification of subcutaneous white adipose tissue inflammation by omega-3 fatty acids is limited in human obesity-a double blind, randomised clinical trial.

BACKGROUND: Obesity is associated with enhanced inflammation. However, investigation in human subcutaneous white adipose tissue (scWAT) is limited and the mechanisms by which inflammation occurs have not been well elucidated. Marine long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have anti-inflammatory actions and may reduce scWAT inflammation. METHODS: Subcutaneous white adipose tissue (scWAT) biopsies were collected from individuals living with obesity (n=45) and normal weight individuals (n=39) prior to and following a 12-week intervention with either 3 g/day of a fish oil concentrate (providing 1.1 g eicosapentaenoic acid (EPA) + 0.8 g docosahexaenoic acid (DHA)) or 3 g/day of corn oil. ScWAT fatty acid, oxylipin, and transcriptome profiles were assessed by gas chromatography, ultra-pure liquid chromatography tandem mass spectrometry, RNA sequencing and qRT-PCR, respectively. FINDINGS: Obesity was associated with greater scWAT inflammation demonstrated by lower concentrations of specialised pro-resolving mediators (SPMs) and hydroxy-DHA metabolites and an altered transcriptome with differential expression of genes involved in LC n-3 PUFA activation, oxylipin synthesis, inflammation, and immune response. Intervention with LC n-3 PUFAs increased their respective metabolites including the SPM precursor 14-hydroxy-DHA in normal weight individuals and decreased arachidonic acid derived metabolites and expression of genes involved in immune and inflammatory response with a greater effect in normal weight individuals. INTERPRETATION: Downregulated expression of genes responsible for fatty acid activation and metabolism may contribute to an inflammatory oxylipin profile and limit the effects of LC n-3 PUFAs in obesity. There may be a need for personalised LC n-3 PUFA supplementation based on obesity status. FUNDING: European Commission Seventh Framework Programme (Grant Number 244995) and Czech Academy of Sciences (Lumina quaeruntur LQ200111901).

Dysregulation of Subcutaneous White Adipose Tissue Inflammatory Environment Modelling in Non-Insulin Resistant Obesity and Responses to Omega-3 Fatty Acids - A Double Blind, Randomised Clinical Trial.

Background: Obesity is associated with enhanced lipid accumulation and the expansion of adipose tissue accompanied by hypoxia and inflammatory signalling. Investigation in human subcutaneous white adipose tissue (scWAT) in people living with obesity in which metabolic complications such as insulin resistance are yet to manifest is limited, and the mechanisms by which these processes are dysregulated are not well elucidated. Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) have been shown to modulate the expression of genes associated with lipid accumulation and collagen deposition and reduce the number of inflammatory macrophages in adipose tissue from individuals with insulin resistance. Therefore, these lipids may have positive actions on obesity associated scWAT hypertrophy and inflammation. Methods: To evaluate obesity-associated tissue remodelling and responses to LC n-3 PUFAs, abdominal scWAT biopsies were collected from normal weight individuals and those living with obesity prior to and following 12-week intervention with marine LC n-3 PUFAs (1.1 g EPA + 0.8 g DHA daily). RNA sequencing, qRT-PCR, and histochemical staining were used to assess remodelling- and inflammatory-associated gene expression, tissue morphology and macrophage infiltration. Results: Obesity was associated with scWAT hypertrophy (P < 0.001), hypoxia, remodelling, and inflammatory macrophage infiltration (P = 0.023). Furthermore, we highlight the novel dysregulation of Wnt signalling in scWAT in non-insulin resistant obesity. LC n-3 PUFAs beneficially modulated the scWAT environment through downregulating the expression of genes associated with inflammatory and remodelling pathways (P <0.001), but there were altered outcomes in individuals living with obesity in comparison to normal weight individuals. Conclusion: Our data identify dysregulation of Wnt signalling, hypoxia, and hypertrophy, and enhanced macrophage infiltration in scWAT in non-insulin resistant obesity. LC n-3 PUFAs modulate some of these processes, especially in normal weight individuals which may be preventative and limit the development of restrictive and inflammatory scWAT in the development of obesity. We conclude that a higher dose or longer duration of LC n-3 PUFA intervention may be needed to reduce obesity-associated scWAT inflammation and promote tissue homeostasis. Clinical Trial Registration: www.isrctn.com, identifier ISRCTN96712688.

Glucose-Dependent Insulinotropic Polypeptide Plasma Level Influences the Effect of n-3 PUFA Supplementation.

Elevated glucose-dependent insulinotropic peptide (GIP) levels in obesity may predict the metabolic benefits of n-3 PUFA supplementation. This placebo-controlled trial aimed to analyze fasting and postprandial GIP response to 3-month n-3 PUFA supplementation (1.8 g/d; DHA:EPA, 5:1) along with caloric restriction (1200-1500 kcal/d) in obese subjects. Compliance was confirmed by the incorporation of DHA and EPA into red blood cells (RBCs). Blood analyses of glucose, insulin, non-esterified fatty acids (NEFAs), GIP and triglycerides were performed at fasting, and during an oral glucose tolerance test and a high fat mixed-meal tolerance test. Fatty acid composition of RBC was assessed by gas chromatography and total plasma fatty acid content and composition was measured by gas-liquid chromatography. The DHA and EPA content in RBCs significantly increased due to n-3 PUFA supplementation vs. placebo (77% vs. -3%, respectively). N-3 PUFA supplementation improved glucose tolerance and decreased circulating NEFA levels (0.750 vs. 0.615 mmol/L), as well as decreasing plasma saturated (1390 vs. 1001 µg/mL) and monounsaturated (1135 vs. 790 µg/mL) fatty acids in patients with relatively high GIP levels. The effects of n-3 PUFAs were associated with the normalization of fasting (47 vs. 36 pg/mL) and postprandial GIP levels. Obese patients with elevated endogenous GIP could be a target group for n-3 PUFA supplementation in order to achieve effects that obese patients without GIP disturbances can achieve with only caloric restriction.

Evaluation of Preconception Dietary Patterns in Women Enrolled in a Multisite Study.

Background: Diet indices are widely used in nutritional research across communities but do not "capture" the full extent of diet variability across multiple countries. Empirically derived dietary patterns can provide additional information because they reflect combinations of foods potentially associated with health outcomes. Limited studies have evaluated preconception dietary patterns in heterogeneous populations. Objectives: In the multisite Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health (NiPPeR) study, the secondary aims included: 1) derive pooled and site-specific preconception dietary patterns, and 2) evaluate these patterns using anthropometric measures and metabolic biomarkers. Methods: Women planning pregnancy (n = 1720) in the United Kingdom, Singapore, and New Zealand completed interviewer-administered harmonized FFQs and lifestyle questionnaires at recruitment. Across-cohort ("pooled") and site-specific dietary patterns were derived, and associations between dietary pattern scores and BMI, waist-to-hip ratio, plasma lipids, and glycemia assessed using multivariable linear regression, expressing results as SD change in outcome per SD change in dietary pattern score. Results: The pooled analysis identified 3 dietary patterns: "Vegetables/Fruits/Nuts" ("Healthy"), "Fried potatoes/Processed meat/Sweetened beverages" ("Less Healthy"), and "Fish/Poultry/Noodles/Rice" ("Mixed"). The "Healthy" and "Less Healthy" pooled pattern scores were highly correlated with their corresponding site-specific dietary pattern scores ("Healthy": ρ = 0.87-0.93; "Less Healthy": ρ = 0.65-0.88). Women with higher scores for the "Healthy" pooled pattern had a lower waist-to-hip ratio (standardized ß: -0.10; 95% CI: -0.18, -0.01); those with higher scores for the "Less Healthy" pooled pattern had a higher BMI (standardized ß: 0.17; 95% CI: 0.09, 0.24), higher LDL cholesterol (standardized ß: 0.10; 95% CI: 0.01, 0.19), and less optimal glucose profiles. However, we noted higher adherence to the "Healthy" pooled pattern with higher BMI. Conclusions: The "Healthy" and "Less Healthy" pooled patterns were comparable to the corresponding site-specific patterns. Although the associations between these patterns and objective anthropometric/metabolic measures were largely in the expected directions, future studies are required to confirm these findings.This trial is registered at clinicaltrials.gov (NCT02509988).

Omega-3 Polyunsaturated Fatty Acids and the Intestinal Epithelium-A Review.

Epithelial cells (enterocytes) form part of the intestinal barrier, the largest human interface between the internal and external environments, and responsible for maintaining regulated intestinal absorption and immunological control. Under inflammatory conditions, the intestinal barrier and its component enterocytes become inflamed, leading to changes in barrier histology, permeability, and chemical mediator production. Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) can influence the inflammatory state of a range of cell types, including endothelial cells, monocytes, and macrophages. This review aims to assess the current literature detailing the effects of ω-3 PUFAs on epithelial cells. Marine-derived ω-3 PUFAs, eicosapentaenoic acid and docosahexaenoic acid, as well as plant-derived alpha-linolenic acid, are incorporated into intestinal epithelial cell membranes, prevent changes to epithelial permeability, inhibit the production of pro-inflammatory cytokines and eicosanoids and induce the production of anti-inflammatory eicosanoids and docosanoids. Altered inflammatory markers have been attributed to changes in activity and/or expression of proteins involved in inflammatory signalling including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), peroxisome proliferator activated receptor (PPAR) α and γ, G-protein coupled receptor (GPR) 120 and cyclooxygenase (COX)-2. Effective doses for each ω-3 PUFA are difficult to determine due to inconsistencies in dose and time of exposure between different in vitro models and between in vivo and in vitro models. Further research is needed to determine the anti-inflammatory potential of less-studied ω-3 PUFAs, including docosapentaenoic acid and stearidonic acid.

Long-Chain Polyunsaturated Fatty Acids (LCPUFAs) and the Developing Immune System: A Narrative Review.

The immune system is complex: it involves many cell types and numerous chemical mediators. An immature immune response increases susceptibility to infection, whilst imbalances amongst immune components leading to loss of tolerance can result in immune-mediated diseases including food allergies. Babies are born with an immature immune response. The immune system develops in early life and breast feeding promotes immune maturation and protects against infections and may protect against allergies. The long-chain polyunsaturated fatty acids (LCPUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) are considered to be important components of breast milk. AA, eicosapentaenoic acid (EPA) and DHA are also present in the membranes of cells of the immune system and act through multiple interacting mechanisms to influence immune function. The effects of AA and of mediators derived from AA are often different from the effects of the n-3 LCPUFAs (i.e., EPA and DHA) and of mediators derived from them. Studies of supplemental n-3 LCPUFAs in pregnant women show some effects on cord blood immune cells and their responses. These studies also demonstrate reduced sensitisation of infants to egg, reduced risk and severity of atopic dermatitis in the first year of life, and reduced persistent wheeze and asthma at ages 3 to 5 years, especially in children of mothers with low habitual intake of n-3 LCPUFAs. Immune markers in preterm and term infants fed formula with AA and DHA were similar to those in infants fed human milk, whereas those in infants fed formula without LCPUFAs were not. Infants who received formula plus LCPUFAs (both AA and DHA) showed a reduced risk of allergic disease and respiratory illness than infants who received standard formula. Studies in which infants received n-3 LCPUFAs report immune differences from controls that suggest better immune maturation and they show lower risk of allergic disease and respiratory illness over the first years of life. Taken together, these findings suggest that LCPUFAs play a role in immune development that is of clinical significance, particularly with regard to allergic sensitisation and allergic manifestations including wheeze and asthma.

The Effect of Caloric Restriction with and without n-3 PUFA Supplementation on Bone Turnover Markers in Blood of Subjects with Abdominal Obesity: A Randomized Placebo-Controlled Trial.

Weight loss contributes to an increased risk of hip fracture, especially in postmenopausal women. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation could diminish the adverse effect of weight loss on bone health. The aim of this randomized, placebo-controlled, double-blind parallel trial was to investigate the effect of caloric restriction and n-3 PUFA supplement intake on osteogenic markers (carboxylated osteocalcin (Gla-OC); procollagen I N-terminal propeptide (PINP)), as well as a bone resorption marker (C-terminal telopeptide of type I collagen (CTX-I)) in a serum of 64 middle aged individuals (BMI 25-40 kg/m2) with abdominal obesity. Bone remodeling, metabolic and inflammatory parameters and adipokines were determined before and after 3 months of an isocaloric diet (2300-2400 kcal/day) or a low-calorie diet (1200 kcal/day for women and 1500 kcal/day for men) along with n-3 PUFA (1.8 g/day) or placebo capsules. CTX-I and adiponectin concentrations were increased following 7% weight loss independently of supplement use. Changes in CTX-I were positively associated with changes in adiponectin level (rho = 0.25, p = 0.043). Thus, an increase in serum adiponectin caused by body weight loss could adversely affect bone health. N-3 PUFAs were without effect.