Mechanisms of Colonisation and Colonisation Resistance of the Digestive Tract Part 1: Bacteria/host Interactions

The digestive microflora is characterized by a high degree of complexity and diversity. Variation in the composition of the digestive flora of an individual occurs in space and time. Two kinds of s..

Serum fatty acid profile does not reflect seafood intake in adolescents with atopic eczema.

AIM: Long-chain polyunsaturated fatty acids (LCPUFAs) are immunomodulatory, but their role in allergy development is controversial. We investigated whether proportions of LCPUFAs in serum phospholipids were related to allergic diagnosis, seafood intake and LCPUFA proportions in cord blood.</br></br> METHODS: Serum was obtained from 148 birth cohort children at 13 years of age. Forty had atopic eczema, 53 had respiratory allergy, and 55 were nonallergic. Proportions of LCPUFAs were determined in serum phospholipids; cord blood from 128 of the individuals was previously analysed. Seafood intake was estimated using questionnaires.</br></br> RESULTS: Allergic and nonallergic individuals did not differ significantly regarding individual LCPUFAs. However, arachidonic acid over docosahexaenoic acid (DHA) ratio was higher in allergic, compared with nonallergic, adolescents. In nonallergic individuals, LCPUFA proportions in cord serum and adolescent serum correlated weakly. In individuals with atopic eczema and respiratory allergy, these correlations were weak or absent. A moderate correlation between seafood intake and serum DHA was seen in nonallergic individuals and those with respiratory allergy, but not in those with atopic eczema.</br></br> CONCLUSION: Serum LCPUFA pattern was similar in allergic and nonallergic adolescents. Fatty acid metabolism may be altered in atopic eczema subjects, suggested by poor correlations between fatty acid intake and serum levels

Cord Blood Levels of EPA, a Marker of Fish Intake, Correlate with Infants\u27 T- and B-Lymphocyte Phenotypes and Risk for Allergic Disease

Maternal fish intake during pregnancy has been associated with reduced allergy development in the offspring and here, we hypothesized that components of fish stimulate fetal immune maturation. The aim of this study was to investigate how maternal fish intake during pregnancy and levels of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in the infant\u27s cord serum correlated with different subsets of B- and T-cells in cord blood and B-cell activating factor (BAFF) in cord plasma, and with doctor-diagnosed allergy at 3 and 8 years of age in the FARMFLORA birth-cohort consisting of 65 families. Principal component analysis showed that infant allergies at 3 or 8 years of age were negatively associated with the proportions of n-3 LCPUFAs (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) in infant cord serum, which, in turn correlated positively with maternal fish intake during pregnancy. Both maternal fish intake and cord serum n-3 LCPUFAs correlated negatively to CD5(+) B cells and the FOXP3(+)CD25(high) of the CD4(+) T cell subsets in cord blood, but not to BAFF in cord plasma. Our observational study suggests that fish might contain components that promote maturation of the infant\u27s immune system in a manner that protects against allergy development

Exposure to a Farm Environment During Pregnancy Increases the Proportion of Arachidonic Acid in the Cord Sera of Offspring

Growing up in a farm environment is protective against allergy development. Various explanations have been put forward to explain this association. Fatty acids are regulators of immune function and the composition of fatty acids in the circulation system may affect immune development. Here, we investigate whether the fatty acid composition of cord serum differs for infants born to Farm (n = 26) or non-Farm mothers (n =29) in the FARMFLORA birth-cohort. For comparison, the levels of fatty acids in the maternal diet, serum and breast milk around 1 month post-partum were recorded. The fatty acids in the cord sera from infants born to Farm mothers had higher proportions of arachidonic acid (20:4 n-6) and adrenic acid (22:4 n-6) than those from infants born to non-Farm mothers. No differences were found for either arachidonic acid or adrenic acid in the diet, samples of the serum, or breast milk from Farm and non-Farm mothers obtained around 1 month post-partum. The arachidonic and adrenic acid levels in the cord blood were unrelated to allergy outcome for the infants. The results suggest that a farm environment may be associated with the fatty acid composition to which the fetus is exposed during pregnancy

The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro

Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naive T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 muM fatty acids; alpha-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNgamma. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells

Umbilical cord blood metabolome differs in relation to delivery mode, birth order and sex, maternal diet and possibly future allergy development in rural children

Allergy is one of the most common diseases among young children yet all factors that affect development of allergy remain unclear. In a small cohort of 65 children living in the same rural area of south-west Sweden, we have previously found that maternal factors, including prenatal diet, affect childhood allergy risk, suggesting that in utero conditions may be important for allergy development. Here, we studied if metabolites in the umbilical cord blood of newborns may be related to development of childhood allergy, accounting for key perinatal factors such as mode of delivery, birth order and sex. Available umbilical cord blood plasma samples from 44 of the participants were analysed using gas chromatography-mass spectrometry metabolomics; allergy was diagnosed by specialised paediatricians at ages 18 months, 3 years and 8 years and included eczema, asthma, food allergy and allergic rhinoconjunctivitis. Nineteen cord blood metabolites were related to future allergy diagnosis though there was no clear pattern of up- or downregulation of metabolic pathways. In contrast, perinatal factors birth order, sex and mode of delivery affected several energy and bio-synthetic pathways, including glutamate and aspartic acid—histidine metabolism (p = 0.004) and the tricarboxylic acid cycle (p = 0.006) for birth order; branched chain amino acid metabolism (p = 0.0009) and vitamin B6 metabolism (p = 0.01) for sex; and glyoxylate and dicarboxylic acid metabolism (p = 0.005) for mode of delivery. Maternal diet was also related to some of the metabolites associated with allergy. In conclusion, the cord blood metabolome includes individual metabolites that reflect lifestyle, microbial and other factors that may be associated with future allergy diagnosis, and also reflects temporally close events/factors. Larger studies are required to confirm these associations, and perinatal factors such as birth order or siblings must be considered in future cord-blood metabolome studies

Diet in 1-year-old farm and control children

BACKGROUND: A farming environment confers strong protection against allergy development. We have previously shown that farming mothers consume more full-fat dairy than control mothers, who instead consume more low-fat dairy, margarine, and oils; margarine and oil intake was associated with increased risk of allergy development in their children. OBJECTIVES: The aims of this study were to investigate the differences in diet between children in farming and control families at 1 year of age, to investigate the relation between the diets of the mothers and their children, and to relate the children's diet to allergy development. DESIGN: The diet of 1-year-old children from dairy farming families (n=28) and from control families in the same rural area (n=37) was assessed by 24-h dietary recalls, followed by 24-h food diaries. Allergy was diagnosed by pediatricians at 3 years of age using strict predefined criteria. RESULTS: Farm children had a higher intake of farm milk, whole cream, cholesterol, saturated fat, and fat in total and tended to eat more butter, while controls consumed more carbohydrates and poultry and tended to eat more margarine. Farm children also had higher intakes of homemade porridge/gruel, oily fish, and iodine. The intake of butter and whole milk in children and mothers correlated significantly in farm families but not in controls. A weak negative association was found between seafood intake and allergy development, while allergy was positively associated with the intake of pork as well as zinc in the control group; these intakes also correlated with each other. CONCLUSIONS: Consistent with mothers in farming families, the children consumed more full-fat dairy and saturated fat than did controls, but this could not be linked to the low risk of allergy in the farming group. Seafood intake might protect against allergy development, in accordance with earlier findings

Thyroid hormones in relation to toxic metal exposure in pregnancy, and potential interactions with iodine and selenium

Background: Several endocrine-disrupting metals may affect thyroid function, but the few available studies of exposure during pregnancy and thyroid hormones are inconclusive. Objective: To explore if environmental exposure to cadmium (Cd), lead (Pb), and methylmercury (MeHg) impacts thyroid function in pregnancy, and interacts with iodine and selenium status. Methods: Women in a Swedish birth cohort provided blood and urine samples in early third trimester. Concentrations of erythrocyte Cd, Pb, and Hg (n = 544), urinary Cd and iodine (n = 542) and plasma selenium (n = 548) were measured using inductively coupled plasma-mass spectrometry. Free and total thyroxine (fT4, tT4) and triiodothyronine (fT3, tT3), and thyroid stimulating hormone (TSH), were measured in plasma (n = 548) with electrochemiluminescence immunoassays. Metal-hormone associations were assessed in regression models, and metal mixture effects and metal-nutrient interactions were explored in Bayesian kernel machine regression (BKMR). Results: In multivariable-adjusted regression models, a doubling of urinary Cd was associated with a mean increase in tT4 of 2.7 nmol/L (95% CI: 0.78, 4.6), and in fT3 and tT3 of 0.06 pmol/L (0.02, 0.10) and 0.09 nmol/L (0.05, 0.13), respectively. A doubling of urinary Cd was associated with a −0.002 (−0.003, −0.001) and −0.03 (−0.05, −0.02) decrease in the fT4:tT4 and fT3:tT3 ratio, respectively. A doubling of erythrocyte Hg (&gt;1 \ub5g/kg) was associated with a decrease in fT3 and tT3 by −0.11 pmol/L (−0.16, −0.05) and −0.11 nmol/L (−0.16, −0.06), respectively, and a −0.013 (−0.02, −0.01) decrease in the fT3:fT4 ratio. BKMR did not indicate any mixture effect of toxic metals or interactions between metals and iodine or selenium in relation to the hormones. Conclusion: Our findings suggest that exposure to Cd and Hg, at levels globally prevalent through the diet, may affect thyroid function during pregnancy, independently of iodine and selenium levels. Further studies on potential implications for maternal and child health are warranted

Mediation by Thyroid Hormone in the Relationships Between Gestational Exposure to Methylmercury and Birth Size

Our previous studies have linked gestational methylmercury exposure, originating from seafood, to changes in maternal thyroid hormones and infant birth size in a Swedish birth cohort. Herein we aimed to determine associations between maternal thyroid hormones and infant birth size and elucidate if maternal hormones could mediate the relationship between methylmercury and lower birth size. In 515 women, without known thyroid disease, we assessed metal exposure by erythrocyte mercury concentrations (mainly methylmercury, reflecting exposure over the past months) in early third trimester measured with inductively coupled plasma-mass spectrometry. Plasma concentrations of total and free thyroxine (tT4 and fT4) and triiodothyronine (tT3 and fT3), and thyroid-stimulating hormone (TSH) were measured at an accredited clinical laboratory. In multivariable-adjusted linear regression models, maternal tT3 (per 1\ua0nmol/L increase) was positively associated with birth weight (B: 125\ua0g; 95% CI 36, 214) and length (B: 0.59\ua0cm; 95% CI 0.21, 0.97). Maternal fT4 was inversely associated with birth weight (B: −\ua033\ua0g; 95% CI −\ua057, −\ua09.5), driven by obese women (n = 76). Causal mediation analyses suggested that a doubling of erythrocyte mercury (&gt; 1\ua0\ub5g/kg; n = 374) was associated with a mean tT3-mediated decrease in birth weight of 11\ua0g (95% CI −\ua025, −\ua01.6) and in birth length of 0.1\ua0cm (95% CI −\ua00.12, −\ua00.01), both equivalent to about 12% of the total effect. To conclude, tT3 was positively associated with infant birth size. Reduced tT3 levels appeared to mediate a minor part of the inverse association between methylmercury exposure and birth size

Biomarkers of seafood intake during pregnancy – Pollutants versus fatty acids and micronutrients

Intake of fish and seafood during pregnancy may have certain beneficial effects on fetal development, but measurement of intake using questionnaires is unreliable. Here, we assessed several candidate biomarkers of seafood intake, including long-chain omega 3 fatty acids (n-3 LCPUFA), selenium, iodine, methylmercury, and different arsenic compounds, in 549 pregnant women (gestational week 29) in the prospective birth cohort NICE (Nutritional impact on Immunological maturation during Childhood in relation to the Environment). Proportions of the fatty acids eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) in erythrocytes were measured using gas chromatography with flame ionization detector. Selenium was measured in blood plasma and erythrocytes, mercury and arsenic in erythrocytes, and iodine and several arsenic compounds in urine, using inductively coupled plasma mass spectrometry, arsenic compounds after first being separated by ion exchange high-performance liquid chromatography (HPLC). Each biomarker was related to intake of total seafood and to intake of fatty and lean fish, and shellfish in third trimester, estimated from a semi-quantitative food frequency questionnaire filled out in gestational week 34. The pregnant women reported a median total seafood intake of 184 g/week (5th-95th percentiles: 34–465 g/week). This intake correlated most strongly with erythrocyte mercury concentrations (rho = 0.49, p &lt; 0.001), consisting essentially of methylmercury, followed by total arsenic in erythrocytes (rho = 0.34, p &lt; 0.001), and arsenobetaine in urine (rho = 0.33, p &lt; 0.001), the main form of urinary arsenic. These biomarkers correlated well with intake of both fatty fish, lean fish, and shellfish. Erythrocyte DHA and plasma selenium correlated, although weakly, mainly with fatty fish (rho = 0.25 and 0.22, respectively, both p &lt; 0.001). In conclusion, elevated concentrations of erythrocyte mercury and urinary arsenobetaine can be useful indicators of seafood intake, more so than the n-3 LCPUFAs. However, the relative importance of the biomarkers may differ depending on the type and amount of seafood consumed