Micronutrient supplement recommendations in pregnancy vary across a geographically diverse range of countries: a narrative review.

Specific food supplements are essential during preconception and pregnancy to ensure adequate intake of vitamins and minerals to support fetal growth and development and metabolic changes in the maternal body. Our objective was to identify food supplement recommendations, particularly those of folic acid, iron, Vitamin D, and iodine, during preconception and/or pregnancy across a geographically diverse range of countries. Further, we investigated whether country location and income-level related to the recommendations. We performed an electronic search and identified country-specific preconception and pregnancy food supplement recommendations, policy documents, and official guidelines of national organizations informing recommendations. To ensure the data were as accurate as possible, country-specific experts were contacted. Data were collected in 2017 and reevaluated in 2022. Country income level was determined by the World Bank classification. Each inspected country (n = 43) recommended folic acid supplementation, typically 400 µg/day, before and during pregnancy. About half of the countries recommended an iron supplement (dose range, 16-195 mg/day) and one quarter Vitamin D (typically 10 µg/d in higher latitudes) and iodine (150-200 µg/day). Country location and income level had some influence on the recommendations. Vitamin D was more often recommended in higher latitude, high-income countries. Almost all upper-middle and lower-middle income countries recommended iron supplementation, whereas less than one third of high-income countries had a corresponding recommendation. Findings suggest that food supplement recommendations for pregnant women vary across countries, likely influenced by geographic location as well as income level. These data may be used in the harmonization of food supplement recommendations.

The impact of fish oil and/or probiotics on serum fatty acids and the interaction with low-grade inflammation in pregnant women with overweight and obesity: secondary analysis of a randomised controlled trial.

N-3 long-chain PUFA (LC-PUFA) and probiotics are generally considered to induce health benefits. The objective was to investigate (1) the impact of fish oil and/or probiotics on serum fatty acids (sFA), (2) the interaction of sFA with low-grade inflammation and (3) the relation of sFA to the onset of gestational diabetes mellitus (GDM). Pregnant women with overweight/obesity were allocated into intervention groups with fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo in early pregnancy (fish oil: 1·9 g DHA and 0·22 g EPA, probiotics: Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 CFU, each daily). Blood samples were collected in early (n 431) and late pregnancy (n 361) for analysis of fatty acids in serum phosphatidylcholine (PC), cholesteryl esters (CE), TAG and NEFA with GC and high-sensitivity C-reactive protein and GlycA by immunoassay and NMR spectroscopy, respectively. GDM was diagnosed according to 2 h 75 g oral glucose tolerance test. EPA in PC, CE and TAG and DHA in PC, CE, TAG and NEFA were higher in fish oil and fish oil + probiotics groups compared with placebo. EPA in serum NEFA was lower in women receiving probiotics compared with women not receiving. Low-grade inflammation was inversely associated with n-3 LC-PUFA, which were related to an increased risk of GDM. Fish oil and fish oil + probiotics consumption increase serum n-3 LC-PUFA in pregnant women with overweight/obesity. Although these fatty acids were inversely related to inflammatory markers, n-3 LC-PUFA were linked with an increased risk for GDM.

Maternal fish oil and/or probiotics intervention: Allergic diseases in children up to two years old.

BACKGROUND: As n-3 long-chain polyunsaturated fatty acids and probiotics possess immunomodulatory properties, theoretically they could lower the risk of allergic diseases. But their effects remain controversial. We aimed to study the effects of fish oil and probiotics separately or in combination from early pregnancy onwards to lower the risk of allergic diseases in the infants. METHODS: In this double-blind trial, women (n = 439) in early pregnancies were randomized into four intervention groups: fish oil + placebo, probiotics + placebo, fish oil + probiotics, and placebo + placebo. Fish oil (1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid) and probiotic (Lacticaseibacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each) supplements were provided for daily consumption from randomization up to 6 months postpartum. All analyses were adjusted with pet ownership. RESULTS: No difference between the infants in the four intervention groups were found regarding physician-diagnosed food allergy, atopic eczema, or atopy at the age of 12 or 24 months (all p > .05). The probiotic intervention was associated with lower odds of recurrent wheezing at 24 months (OR 0.39, 95% CI 0.18-0.84, p = .017), but not at 12 months. CONCLUSIONS: The use of fish oil and/or probiotics from early pregnancy onwards did not lower the odds of childhood allergic diseases or atopy, with the exception of the probiotic intervention which decreased the risk of recurrent wheezing when the infants were two years old. This suggests that the incidence of asthma could also decrease later in childhood and thus these outcomes need to be clarified in further investigations.

The Effect of a Fish Oil and/or Probiotic Intervention from Early Pregnancy Onwards on Colostrum Immune Mediators: A Randomized, Placebo-Controlled, Double-Blinded Clinical Trial in Overweight/Obese Mothers.

SCOPE: Modifying the composition of colostrum by external factors may provide opportunities to improve the infant's health. Here, we evaluated how fish oil and/or probiotics supplementation modify concentrations of colostrum immune mediators and their associations with perinatal clinical factors on mothers with overweight/obesity. METHODS AND RESULTS: Pregnant women were randomized in a double-blind manner into four intervention groups, and the supplements were consumed daily from early pregnancy onwards. Colostrum samples were collected from 187 mothers, and 16 immune mediators were measured using bead-based immunoassays. Interventions modified colostrum composition; the fish oil+probiotics group had higher concentrations of IL-12p70 than probiotics+placebo and higher FMS-like tyrosine kinase 3 ligand (FLT-3L) than fish oil+placebo and probiotics+placebo (one-way analysis of variance, post-hoc Tukey's test). Although the fish oil+probiotics group had higher levels of IFNα2 compared to the fish oil+placebo group, these differences were not statistically significant after correction for multiple testing. Multivariate linear model revealed significant associations between several immune mediators and the perinatal use of medication. CONCLUSION: Fish oil/probiotics intervention exerted a minor effect on concentrations of colostrum immune mediators. However, medication during the perinatal period modulated the immune mediators. These changes in colostrum's composition may contribute to immune system development in the infant.

The immune-supportive diet in allergy management: A narrative review and proposal.

The role of nutrition is increasingly recognized in the management of chronic immune diseases. However, the role of an immune-supportive diet as adjuvant therapy in the management of allergic disease has not been similarly explored. This review assesses the existing evidence for a relationship between nutrition, immune function, and allergic disease from a clinical perspective. In addition, the authors propose an immune-supportive diet to enhance dietary interventions and complementing other therapeutic options for allergic disease from early life to adulthood. A narrative review of the literature was conducted, to determine the evidence of the relationship between nutrition and immune function, overall health, epithelial barrier function, and gut microbiome, particularly in relation to allergy. Studies on food supplements were excluded. The evidence was assessed and utilized to develop a sustainable immune-supportive diet to complement other therapies in allergic disease. The proposed diet consists of a highly diverse range of fresh, whole, and minimally processed plant-based and fermented foods supplemented with moderate amounts of nuts, omega-3-rich foods and animal-based products in proportional amounts of the EAT-Lancet diet, such as (fatty) fish, (fermented) milk products which may be full-fat and eggs, lean meat or poultry, which may be free-range or organic.

Food Supplement Use Differs from the Recommendations in Pregnant Women: A Multinational Survey.

The aim was to investigate, among pregnant women, (1) the use of food supplements and (2) the awareness of food supplement recommendations and beliefs about food supplement use in four European countries: Finland, Italy, Poland, and the United Kingdom. The participants (n = 1804) completed an online questionnaire with predefined statements. Daily intakes of vitamins and minerals were calculated using uploaded pictures or weblinks of the supplement packages. Country differences were assessed. Most participants (91%) used at least one food supplement during pregnancy. A prenatal multivitamin was the most commonly used supplement type (84% of the users), and 75% of the participants thought consumption of multivitamin is recommended. Of the participants, 81% knew that folic acid is recommended during pregnancy while 58% knew the recommendation for vitamin D. In 19% of the supplement users, the daily safe upper intake limit of at least one nutrient was exceeded. Nevertheless, most participants agreed that they knew which supplements (91%) and doses of supplements (87%) needed to be used during pregnancy. To conclude, the majority of the participants used food supplements, but lower proportions knew and adhered to the recommended intakes. Between-country differences were observed in the use and knowledge of and beliefs regarding supplements. The results suggest a need for assessment and monitoring of supplement use in antenatal care to ensure appropriate use.

Iodine status in pregnant women and infants in Finland.

PURPOSE: Iodine insufficiency during pregnancy may adversely influence fetal growth and development. There is a lack of information on iodine status in pregnant women and infants in many countries including Finland. The aim of this study is to determine dietary intake of iodine and the iodine status in a population of Finnish pregnant women and their infants. METHODS: Urine samples were collected from women participating in a mother-child clinical study at early (n = 174) and late pregnancy (n = 186) and at three months of postpartum (n = 197), when infant samples were also collected (n = 123). Urine iodine concentration was measured using inductively coupled plasma mass spectrometry. Cutoffs for iodine insufficiency were < 150 µg/L during pregnancy and < 100 µg/L at postpartum and in infants. Iodine intake was assessed using 3-day food diaries. RESULTS: Increased risk of insufficiency, based on urinary iodine concentrations, was observed in the groups investigated in this study. Of the women studied, 66% had urinary iodine concentrations indicating insufficient intakes and iodine insufficiency at early pregnancy, 70% at late pregnancy and 59% at three months of postpartum. This was also the case in 29% of the three-month-old infants. Estimation of iodine intake revealed that iodine insufficient women had lower intakes of iodine from the diet, from food supplements and from diet plus supplements than iodine sufficient women in early pregnancy and at three months of post-partum. In late pregnancy, this difference was seen for iodine intake from supplements. CONCLUSION: The majority of the women manifested with low urine iodine concentrations both during and after pregnancy. Similarly, one-third of the infants presented with iodine insufficiency. Maternal iodine intake data support these findings. These observations may have implications for optimal child cognitive development.

Serum CathepsinD in pregnancy: Relation with metabolic and inflammatory markers and effects of fish oils and probiotics.

BACKGROUND AND AIMS: Elevated circulating levels of CathepsinD (CatD) have been linked to metabolic deviations including liver inflammation. We investigated 1) whether supplementation with probiotics and/or fish oil affects CatD and 2) whether the CatD concentration would associate with gestational diabetes (GDM), low-grade inflammation, lipid metabolism, body fat % and dietary composition. METHODS AND RESULTS: Overweight/obese pregnant women (n = 438) were randomized into fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo groups. Fish oil contained 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid and probiotics were Lacticaseibacillusrhamnosus HN001 (formerly Lactobacillusrhamnosus HN001) and Bifidobacteriumanimalis ssp. lactis 420, 1010 colony-forming units each). Serum CatD levels were analysed by ELISA, GlycA and lipid metabolites by NMR, high sensitive C-reactive protein (hsCRP) by immunoassay, and intakes of energy yielding nutrients and n-3 and n-6 fatty acids from food diaries at both early and late pregnancy. GDM was diagnosed by OGTT. CatD concentrations did not differ between the intervention groups or by GDM status. Multivariable linear models revealed that body fat % and GlycA affected CatD differently in healthy women and those with GDM. CONCLUSION: The serum CatD concentration of pregnant women was not modified by this dietary intervention. Serum CatD was influenced by two parameters, body fat and low grade inflammation, which were dependent on the woman's GDM status. CLINICAL TRIAL REG. NO: NCT01922791, clinicaltrials.gov (secondary analysis).

Impact of combined consumption of fish oil and probiotics on the serum metabolome in pregnant women with overweight or obesity.

BACKGROUND: If a pregnant woman is overweight, this can evoke metabolic alterations that may have health consequences for both mother and child. METHODS: Pregnant women with overweight/obesity (n = 358) received fish oil+placebo, probiotics+placebo, fish oil+probiotics or placebo+placebo from early pregnancy onwards. The serum metabolome was analysed from fasting samples with a targeted NMR-approach in early and late pregnancy. GDM was diagnosed by OGTT. FINDINGS: The intervention changed the metabolic profile of the women, but the effect was influenced by their GDM status. In women without GDM, the changes in nine lipids (FDR<0.05) in the fish oil+placebo-group differed when compared to the placebo+placebo-group. The combination of fish oil and probiotics induced changes in more metabolites, 46 of the lipid metabolites differed in women without GDM when compared to placebo+placebo-group; these included reduced increases in the concentrations and lipid constituents of VLDL-particles and less pronounced alterations in the ratios of various lipids in several lipoproteins. In women with GDM, no differences were detected in the changes of any metabolites due to any of the interventions when compared to the placebo+placebo-group (FDR<0.05). INTERPRETATION: Fish oil and particularly the combination of fish oil and probiotics modified serum lipids in pregnant women with overweight or obesity, while no such effects were seen with probiotics alone. The effects were most evident in the lipid contents of VLDL and LDL only in women without GDM. FUNDING: State Research Funding for university-level health research in the Turku University Hospital Expert Responsibility Area, Academy of Finland, the Diabetes Research Foundation, the Juho Vainio Foundation, Janssen Research & Development, LLC.

Metagenomics analysis of gut microbiota in response to diet intervention and gestational diabetes in overweight and obese women: a randomised, double-blind, placebo-controlled clinical trial.

OBJECTIVE: Gut microbiota and diet are known to contribute to human metabolism. We investigated whether the metagenomic gut microbiota composition and function changes over pregnancy are related to gestational diabetes mellitus (GDM) and can be modified by dietary supplements, fish oil and/or probiotics. DESIGN: The gut microbiota of 270 overweight/obese women participating in a mother-infant clinical study were analysed with metagenomics approach in early (mean gestational weeks 13.9) and late (gestational weeks 35.2) pregnancy. GDM was diagnosed with a 2 hour 75 g oral glucose tolerance test. RESULTS: Unlike women with GDM, women without GDM manifested changes in relative abundance of bacterial species over the pregnancy, particularly those receiving the fish oil + probiotics combination. The specific bacterial species or function did not predict the onset of GDM nor did it differ according to GDM status, except for the higher abundance of Ruminococcus obeum in late pregnancy in the combination group in women with GDM compared with women without GDM. In the combination group, weak decreases over the pregnancy were observed in basic bacterial housekeeping functions. CONCLUSIONS: The specific gut microbiota species do not contribute to GDM in overweight/obese women. Nevertheless, the GDM status may disturb maternal gut microbiota flexibility and thus limit the capacity of women with GDM to respond to diet, as evidenced by alterations in gut microbiota observed only in women without GDM. These findings may be important when considering the metabolic complications during pregnancy, but further studies with larger populations are called for to verify the findings.

Weight gain and body composition during pregnancy: a randomised pilot trial with probiotics and/or fish oil.

We evaluated the effects of fish oil and/or probiotic supplementation in a randomised placebo-controlled intervention pilot trial on gestational weight gain (GWG) and body composition. Additionally, the influence of gestational diabetes (GDM) on GWG and body composition was assessed. We randomised 439 overweight women into intervention groups: fish oil + placebo, probiotics + placebo, fish oil + probiotics and placebo + placebo (fish oil: 1·9 g DHA and 0·22 g EPA and probiotics: Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each). GDM was diagnosed with oral glucose tolerance test. Body composition was measured with air displacement plethysmography at randomisation (mean 13·9) and in late pregnancy (mean 35·2 gestational weeks). Intervention did not influence mean GWG or change in body fat mass/percentage (P > 0·17). Body composition in early pregnancy did not differ between the women who did or did not develop GDM (adjusted P > 0·23). Compared with the normoglycaemic women (n 278), women diagnosed with GDM (n 119) gained less weight (7·7 (sd 0·4) v. 9·3 (sd 0·4) kg, adjusted mean difference -1·66 (95 % CI -2·52, -0·80) and fat mass (0·4 (sd 0·4) v. 1·8 (sd 0·3) kg, adjusted mean difference -1·43 (95 % CI -2·19, -0·67) during the follow-up. In conclusion, adiposity of pregnant overweight women was not affected by supplementation with fish oil and/or probiotics, nor did it predict the development of GDM. However, adiposity was reduced in women with GDM compared with normoglycaemic women irrespective of the dietary intervention.

The Impacts of Fish Oil and/or Probiotic Intervention on Low-Grade Inflammation, IGFBP-1 and MMP-8 in Pregnancy: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

BACKGROUND: We investigated the impact of fish oil and/or probiotics on serum and vaginal inflammatory and metabolic proteins and their relation to the onset of gestational diabetes mellitus (GDM). METHODS: Overweight/obese pregnant women received fish oil + placebo, probiotics + placebo, fish oil + probiotics or placebo + placebo from early pregnancy until six months postpartum (fish oil: 1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid; probiotics: Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each). Serum high sensitivity C-reactive protein (hsCRP) and serum/vaginal (s/v) phosphorylated insulin-like growth factor binding-protein-1 (phIGFBP-1), IGFBP-1 and matrix metalloproteinase 8 (MMP-8) were analyzed. GDM was diagnosed according to 2 h 75 g OGTT. RESULTS: The intervention had no impact on the change in proteins during pregnancy. Nevertheless, s-MMP-8 decreased and s-IGFBP-1 increased more in obese than in overweight women in the fish oil + probiotics group, while a decrease in s-MMP-8 was seen in obese women and an increase was seen in overweight women in the probiotics + placebo group. The late pregnancy s-phIGFBP-1 was higher in women who developed GDM in fish oil + probiotics-group compared to fish oil + placebo-group. The concentrations of s-phIGFBP-1 (635.9 ± 315.3 ng/mL vs. 753.2 ± 335.1 ng/mL, p = 0.005) and s-IGFBP-1 (3.78 ± 0.72 ng/mL vs. 3.96 ± 0.69 ng/mL, p = 0.042) were lower in early pregnancy in women who developed GDM than in women remaining healthy. CONCLUSIONS: The intervention per se had no impact on the proteins, but obesity and GDM may modify the effect. IGFBPs may affect the development of GDM.

Efficacy of Fish Oil and/or Probiotic Intervention on the Incidence of Gestational Diabetes Mellitus in an At-Risk Group of Overweight and Obese Women: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

OBJECTIVE: To assess whether the risk of gestational diabetes mellitus (GDM) may be lowered and glucose metabolism improved by daily administration of fish oil and/or probiotic supplements in overweight and obese pregnant women. RESEARCH DESIGN AND METHODS: We randomized in a double-blind manner 439 women (mean 13.9 ± 2.1 gestational weeks [gw]) into four intervention groups: fish oil + placebo, probiotics + placebo, fish oil + probiotics, and placebo + placebo. Fish oil (1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid) and probiotic supplements (Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each) were provided for daily consumption from randomization beyond delivery. Primary outcomes were the incidence of GDM diagnosed with oral glucose tolerance test targeted at 24-28 gw and the change in fasting glucose between randomization and late pregnancy (mean 35.2 ± 0.9 gw). Insulin concentration, insulin resistance HOMA2-IR index, and pregnancy outcomes were determined, as were adverse effects related to the intervention. Analyses were by intent to treat. RESULTS: No differences were found among the intervention groups in the maternal and neonatal pregnancy outcomes or side effects related to the intervention (P > 0.05). The proportion of women with GDM (94 of 377; fish oil + placebo, 23 of 96, 24.0%; probiotics + placebo, 25 of 99, 25.3%; fish oil + probiotics, 26 of 91, 28.6%; and placebo + placebo, 20 of 91, 22.0%) and the change in glucose, insulin, or HOMA2-IR (n = 364) did not differ among the intervention groups (P > 0.11 for all comparisons). CONCLUSIONS: An intervention with fish oil and/or probiotics during pregnancy seemed to be both safe and well tolerated but conferred no benefits in lowering the risk of GDM or improving glucose metabolism in overweight and obese women.

Overall Dietary Quality Relates to Gut Microbiota Diversity and Abundance.

Disturbances in gut microbiota homeostasis may have metabolic consequences with potentially serious clinical manifestations. Diet influences the host's metabolic health in several ways, either directly or indirectly by modulating the composition and function of gut microbiota. This study investigated the extent to which dietary quality is reflected in gut microbiota diversity in overweight and obese pregnant women at risk for metabolic complications. Dietary quality was measured by a validated index of diet quality (IDQ) and microbiota composition was analyzed using 16SrRNA gene sequencing from 84 women pregnant less than 18 weeks. The alpha diversity, measured as Chao1, observed operational taxonomic units (OTUs), phylogenetic diversity, and the Shannon index were calculated. The IDQ score correlated positively with the Shannon index (rho = 0.319, p = 0.003), but not with the other indexes. The women who had the highest dietary quality (highest IDQ quartile) had higher gut microbiota diversity in all the investigated indexes, when compared to the women with the lowest dietary quality (lowest IDQ quartile; p < 0.032). Consequently, a higher dietary quality was reflected in a higher gut microbiota diversity. The presented approach may aid in devising new tools for dietary counseling aiming at holistic health, as well as in microbiome studies, to control for dietary variance.

The impact of probiotic supplementation during pregnancy on DNA methylation of obesity-related genes in mothers and their children.

PURPOSE: Dietary supplementation with probiotics during pregnancy has been suggested to decrease the risk for obesity in women after delivery and to minimize excessive weight gain in their children. Epigenetic DNA methylation has been proposed to impact on gene activity, thereby providing a plausible molecular mechanism for a broad range of biological processes and diseases. This pilot study aimed to evaluate whether probiotic supplementation during pregnancy could modify the DNA methylation status of the promoters of obesity and weight gain-related genes in mothers and their children. METHODS: A sample of 15 pregnant women was taken from a prospective, randomized mother and infant nutrition and probiotic study. Seven women received the probiotic supplementation and eight served as controls. The women's and their children's DNA methylation status of obesity (623 genes) and weight gain-related (433) gene promoters were analyzed from blood samples at the mean of 9.8 months (range 6.1-12.7 months) postpartum. RESULTS: Probiotic supplementation led to significantly decreased levels of DNA methylation in 37 gene promoters and increased levels of DNA methylation in one gene promoter in women. In their children, 68 gene promoters were significantly affected consistently with a lower level of DNA methylation in the probiotic group. CONCLUSIONS: On the basis of our pilot study, we suggest that probiotic supplementation during pregnancy may affect the DNA methylation status of certain promoters of obesity and weight gain-related genes both in mothers and their children, thereby providing a potential mechanism for long-lasting health effects.

Perinatal nutrition impacts on the functional development of the visual tract in infants.

BACKGROUND AND OBJECTIVE: We investigated the associations of maternal diet and serum fatty acids during pregnancy and in early infancy on infantile neurodevelopment. METHODS: Pattern-reversal visual evoked potentials (pVEP) as depictors of central nervous system maturation were recorded from 56 children when they were 2 years old. Maternal nutrient intakes were calculated from food diaries and fish consumption from questionnaires collected during pregnancy. Serum phospholipid fatty acids were determined by gas chromatography in late pregnancy and from infants at 1 month of age. RESULTS: The children of the women who consumed fish three or more times per week during the last trimester of pregnancy had a higher pVEP component P100 amplitude for 60' (mean 23.4, SD 8.1) and 30' (mean 20.4, SD 6.7) of arcminute check sizes compared to those who consumed fish 0-2 times per week (mean 15.0, SD 4.8, p = 0.023, adjusted for birth weight and gender p = 0.058 and mean 13.4, SD 2.0, respectively, p = 0.028, adjusted p = 0.072). Maternal and child serum phospholipid fatty acids correlated with child pVEP measurements. CONCLUSION: The results of this small-scale study suggest that fish consumption during pregnancy and perinatal serum fatty acid status may associate with neurodevelopment within visual system during infancy.

Overweight and obesity status in pregnant women are related to intestinal microbiota and serum metabolic and inflammatory profiles.

BACKGROUND: Overweight and obesity may predispose women to clinical complications during their pregnancy. We hypothesize that a higher degree of overweight status is related to a range of aberrations in biomarkers already in early pregnancy. Our objective was to investigate whether intestinal microbiota, serum metabolic and inflammatory profiles differ in relation to the degree of overweight status in pregnant women. METHODS: This study investigated 52 overweight and 47 obese pregnant women in early pregnancy. Fecal samples were analyzed for intestinal microbiota composition by 16S ribosomal RNA gene sequencing and Qiime pipeline. Circulating serum metabolites, including lipids, amino acids and GlycA, a marker of low-grade inflammation, were analyzed by NMR metabolomics and hsCRP was quantified by immunoassay. Serum zonulin levels were analyzed to depict intestinal permeability by Zonulin ELISA kit and LPS activity for endotoxemia by Limulus amebocyte lysate assay. The analyses were adjusted for multiple comparisons using Benjamini-Hochberg procedure for false discovery rate controlling. RESULTS: The relative abundance of bacterial family Prevotellaceae (adjusted P = 0.19) and markers of low-grade inflammation, hsCRP (P = 0.0015) and GlycA (P < 0.001) and three branched chain amino acids (isoleucine, adjusted P = 0.024; leucine, adjusted P = 0.026; valine, adjusted P = 0.10) and one aromatic amino acid (phenylalanine, adjusted P = 0.050) and concentrations of several VLDL particles and lipid measures in several VLDL particles were higher in obese pregnant women compared to their overweight pregnant counterparts (adjusted P < 0.12). In contrast, lipid measures in a few HDL particles and many fatty acids were lower in obese compared to overweight pregnant women (adjusted P < 0.12). CONCLUSIONS: The detected alterations in intestinal microbiota and metabolic and inflammatory profiles related to obesity status may offer new alternative tools to supplement standard clinical measures to predict the risk for metabolic alterations during the early phase of pregnancy.

Gut Microbiota Richness and Composition and Dietary Intake of Overweight Pregnant Women Are Related to Serum Zonulin Concentration, a Marker for Intestinal Permeability.

BACKGROUND: Increased intestinal permeability may precede adverse metabolic conditions. The extent to which the composition of the gut microbiota and diet contribute to intestinal permeability during pregnancy is unknown. OBJECTIVE: The aim was to investigate whether the gut microbiota and diet differ according to serum zonulin concentration, a marker of intestinal permeability, in overweight pregnant women. METHODS: This cross-sectional study included 100 overweight women [mean age: 29 y; median body mass index (in kg/m(2)): 30] in early pregnancy (<17 wk of gestation; median: 13 wk). Serum zonulin (primary outcome) was determined by using ELISA, gut microbiota by 16S ribosomal RNA sequencing, and dietary intake of macro- and micronutrients from 3-d food diaries. The Mann-Whitney U test was used for pairwise comparisons and linear regression and Spearman's nonparametric correlations for relations between serum zonulin and other outcome variables. RESULTS: Women were divided into "low" (<46.4 ng/mL) and "high" (≥46.4 ng/mL) serum zonulin groups on the basis of the median concentration of zonulin (46.4 ng/mL). The richness of the gut microbiota (Chao 1, observed species and phylogenetic diversity) was higher in the low zonulin group than in the high zonulin group (P = 0.01). The abundances of Bacteroidaceae and Veillonellaceae, Bacteroides and Blautia, and Blautia sp. were lower and of Faecalibacterium and Faecalibacterium prausnitzii higher (P < 0.05) in the low zonulin group than in the high zonulin group. Dietary quantitative intakes of n-3 (ω-3) polyunsaturated fatty acids (PUFAs), fiber, and a range of vitamins and minerals were higher (P < 0.05) in women in the low zonulin group than those in the high zonulin group. CONCLUSIONS: The richness and composition of the gut microbiota and the intake of n-3 PUFAs, fiber, and a range of vitamins and minerals in overweight pregnant women are associated with serum zonulin concentration. Modification of the gut microbiota and diet may beneficially affect intestinal permeability, leading to improved metabolic health of both the mother and fetus. This trial was registered at clinicaltrials.gov as NCT01922791.

Bifidobacterium lactis 420 and fish oil enhance intestinal epithelial integrity in Caco-2 cells.

Increased intestinal permeability is a predisposing factor for low-grade inflammation-associated conditions, including obesity and type 2 diabetes. Dietary components may influence intestinal barrier integrity. We hypothesized that the dietary supplements Bifidobacterium lactis 420, Lactobacillus rhamnosus HN001, and fish oil have beneficial impacts on intestinal barrier integrity. In addition, we hypothesized that the coadministration of these components results in synergistic benefits to the integrity of the intestinal barrier. To study this, we investigated the impact of cell-free culture supernatant from dietary supplements B lactis 420 and L rhamnosus HN001, and fish oil, separately and in combination, on intestinal permeability in a CaCo-2 cell model. Administered separately, both B lactis 420 supernatant and fish oil significantly increased the integrity of the intestinal epithelial barrier, as determined by an increase in transepithelial electrical resistance (TEER), whereas L rhamnosus did not. The TEER increase with B lactis 420 was dose dependent. Interestingly, a combination of B lactis 420 supernatant and fish oil negated the increase in TEER of the single components. mRNA expression of tight junction proteins, measured by real-time quantitative polymerase chain reaction, was not altered, but the mRNA expression of myosin light chain kinase increased after fish oil treatment. To conclude, single dietary components, namely, B lactis 420 and fish oil, induced beneficial effects on intestinal barrier integrity in vitro, whereas a combination of 2 beneficial test compounds resulted in a null effect.

Maternal dietary counseling during pregnancy and infant fatty acid profiles.

We aimed to explore whether maternal dietary counseling to increase the intake of unsaturated fatty acids (FA) is reflected in infant FA status. Serum cholesteryl ester (CE) and triacylglycerol (TAG) FA were analyzed from infants of 45 women randomized to receive dietary counseling from the first trimester of pregnancy and 45 control women. Counseling resulted in a higher intake of polyunsaturated FA and a lower intake of saturated FA. The dietary intake was reflected in cord blood TAGs: the n-6 to n-3 FA ratio was lower [mean difference -0.50 (95%CI -0.95 to -0.06)] and the sum of n-3 FA was higher in the intervention than in the control group [1.46 (0.44 to 2.48)% of total FA]. Reasons for the lack of changes in the cord blood CE fraction and FA fractions at 1-month remain unclear, but may indicate that the changes achieved in the maternal diet through counseling were too modest.