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- Lee, Hanna, et al.
(author)
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Metabolic phenotype and microbiome of infants fed formula containing Lactobacillus paracasei strain F-19
- 2022
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In: Frontiers in Pediatrics. - : Frontiers Media S.A.. - 2296-2360. ; 10
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Journal article (peer-reviewed)abstract
- Early childhood nutrition drives the development of the gut microbiota. In contrast to breastfeeding, feeding infant formula has been shown to impact both the gut microbiota and the serum metabolome toward a more unfavorable state. It is thought that probiotics may alter the gut microbiota and hence create a more favorable metabolic outcome. To investigate the impact of supplementation with Lactobacillus paracasei spp. paracasei strain F-19 on the intestinal microbiota and the serum metabolome, infants were fed a formula containing L. paracasei F19 (F19) and compared to a cohort of infants fed the same standard formula without the probiotic (SF) and a breast-fed reference group (BF). The microbiome, as well as serum metabolome, were compared amongst groups. Consumption of L. paracasei F19 resulted in lower community diversity of the gut microbiome relative to the SF group that made it more similar to the BF group at the end of the intervention (4 months). It also significantly increased lactobacilli and tended to increase bifidobacteria, also making it more similar to the BF group. The dominant genus in the microbiome of all infants was Bifidobacterium throughout the intervention, which was maintained at 12 months. Although the serum metabolome of the F19 group was more similar to the group receiving the SF than the BF group, increases in serum TCA cycle intermediates and decreases in several amino acids in the metabolome of the F19 group were observed, which resulted in a metabolome that trended toward the BF group. Overall, L. paracasei F19 supplementation did not override the impact of formula-feeding but did impact the microbiome and the serum metabolome in a way that may mitigate some unfavorable metabolic impacts of formula-feeding.
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- Lee, Hanna, et al.
(author)
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Milk Fat Globule Membrane as a Modulator of Infant Metabolism and Gut Microbiota : A Formula Supplement Narrowing the Metabolic Differences between Breastfed and Formula-Fed Infants
- 2021
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In: Molecular Nutrition & Food Research. - : Wiley-VCH Verlagsgesellschaft. - 1613-4125 .- 1613-4133. ; 65:3
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Journal article (peer-reviewed)abstract
- Scope Milk fat globule membrane (MFGM) is an important component of milk that has previously been removed in the manufacture of infant formulas, but has recently gained attention owing to its potential to improve immunological, cognitive, and metabolic health. The goal of this study is to determine whether supplementing MFGM in infant formula would drive desirable changes in metabolism and gut microbiota to elicit benefits observed in prior studies. Methods and Results The serum metabolome and fecal microbiota are analyzed using H-1 NMR spectroscopy and 16S rRNA gene sequencing respectively in a cohort of Chinese infants given a standard formula or a formula supplemented with an MFGM-enriched whey protein fraction. Supplementing MFGM suppressed protein degradation pathways and the levels of insulinogenic amino acids that are typically enhanced in formula-fed infants while facilitating fatty acid oxidation and ketogenesis, a feature that may favor brain development. MFGM supplementation did not induce significant compositional changes in the fecal microbiota but suppressed microbial diversity and altered microbiota-associated metabolites. Conclusion Supplementing MFGM in a formula reduced some metabolic gaps between formula-fed and breastfed infants.
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- Li, Xiaonan, et al.
(author)
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Feeding Infants Formula With Probiotics or Milk Fat Globule Membrane : A Double-Blind, Randomized Controlled Trial
- 2019
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In: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 7
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Journal article (peer-reviewed)abstract
- Purpose: To evaluate effects on growth and infection rates of supplementing infant formula with the probiotic Lactobacillus paracasei ssp. paracasei strain F19 (F19) or bovine milk fat globule membrane (MFGM).Methods: In a double-blind, randomized controlled trial, 600 infants were randomized to a formula supplemented with F19 or MFGM, or to standard formula (SF). A breastfed group was recruited as reference (n = 200).The intervention lasted from age 21 ± 7 days until 4 months, and infants were followed until age one year.Results: Both experimental formulas were well tolerated and resulted in high compliance. The few reported adverse events were not likely related to formula, with the highest rates in the SF group, significantly higher than for the F19-supplemented infants (p = 0.046). Weight or length gain did not differ during or after the intervention among the formula-fed groups, with satisfactory growth. During the intervention, overall, the experimental formula groups did not have more episodes of diarrhea, fever, or days with fever than the breastfed infants. However, compared to the breastfed infants, the SF group had more fever episodes (p = 0.021) and days with fever (p = 0.036), but not diarrhea. Compared with the breastfed group, the F19-supplemented infants but not the other two formula groups had more visits/unscheduled hospitalizations (p = 0.015) and borderline more episodes of upper respiratory tract infections (p = 0.048).Conclusions: Both the MFGM- and F19-supplemented formulas were safe and well-tolerated, leading to few adverse effects, similar to the breastfed group and unlike the SF group. During the intervention, the MFGM-supplemented infants did not differ from the breastfed infants in any primary outcome.
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- Li, Xiaonan, et al.
(author)
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Serum cytokine patterns are modulated in infants fed formula with probiotics or milk fat globule membranes : A randomized controlled trial
- 2021
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16
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Journal article (peer-reviewed)abstract
- Background: Proteins and lipids of milk fat globule membrane (MFGM) and probiotics are immunomodulatory. We hypothesized that Lactobacillus paracasei ssp. paracasei strain F19 (F19) would augment vaccine antibody and T helper 1 type immune responses whereas MFGM would produce an immune response closer to that of breastfed (BF) infants.Objective: To compare the effects of supplementing formula with F19 or bovine MFGM on serum cytokine and vaccine responses of formula-fed (FF) and BF infants.Design: FF infants were randomized to formula with F19 (n = 195) or MFGM (n = 192), or standard formula (SF) (n = 194) from age 21±7 days until 4 months. A BF group served as reference (n = 208). We analyzed seven cytokines (n = 398) in serum at age 4 months using magnetic bead-based multiplex technology. Using ELISA, we analyzed anti-diphtheria IgG (n = 258) and anti-poliovirus IgG (n = 309) concentrations in serum before and after the second and third immunization, respectively.Results: Compared with SF, the F19 group had greater IL-2 and lower IFN-γ concentrations (p<0.05, average effect size 0.14 and 0.39). Compared with BF, the F19 group had greater IL-2, IL-4 and IL-17A concentrations (p<0.05, average effect size 0.42, 0.34 and 0.26, respectively). The MFGM group had lower IL-2 and IL-17A concentrations compared with SF (p<0.05, average effect size 0.34 and 0.31). Cytokine concentrations were comparable among the MFGM and BF groups. Vaccine responses were comparable among the formula groups.Conclusions: Contrary to previous studies F19 increased IL-2 and lowered IFN-γ production, suggesting that the response to probiotics differs across populations. The cytokine profile of the MFGM group approached that of BF infants, and may be associated with the previous finding that infectious outcomes for the MFGM group in this cohort were closer to those of BF infants, as opposed to the SF group. These immunomodulatory effects support future clinical evaluation of infant formula with F19 or MFGM.
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- Peng, Yongmei, et al.
(author)
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Fatty acid composition of diet, cord blood and breast milk in Chinese mothers with different dietary habits.
- 2009
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In: Prostaglandins, leukotrienes, and essential fatty acids. - : Elsevier BV. - 1532-2823 .- 0952-3278. ; 81:5-6, s. 325-30
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Journal article (peer-reviewed)abstract
- The influence of two different dietary patterns on maternal fatty acid (FA) intake on the composition of umbilical cord blood plasma phospholipids and transitional breast milk was investigated. A 7-day dietary record was completed in the last trimester of pregnancy by women living in an inland and a coastal area of south-eastern China. The FA composition in maternal diet was calculated using the 2002 Chinese food composition database. Cord blood and transitional breast milk samples were collected and their FA composition was analyzed by capillary gas-liquid chromatography. Mothers in the coastal area showed higher intake of long-chain polyunsaturated FA (LCPUFA) including docosahexaenoic acid (DHA, 22:6omega) and eicosapentaenoic acid (EPA,20:5omega3) but lower linoleic acid (LA, 18:2omega6) and alpha-linolenic acid (ALA, 18:3omega3) than the mothers in the inland area. The intake of arachidonic acid (AA, 20:4omega6) did not differ between the two areas. LA, ALA, AA and DHA in breast milk of day 5 reflected the maternal diet except that the EPA content in breast milk at day 5 was similar for the areas. LA, ALA and AA were lower and EPA higher in umbilical cord plasma phospholipids in infants from the costal compared to the inland area. There were significant differences in maternal intakes of FA confirming different dietary habits, which influenced the FA composition of cord plasma phospholipids and transitional breast milk. Since FA influence gene expression the found variation implies that the long-term follow-up of this cohort will be interesting.
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- Qi, Qibin, et al.
(author)
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FTO genetic variants, dietary intake and body mass index : insights from 177 330 individuals
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:25, s. 6961-6972
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Journal article (peer-reviewed)abstract
- FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177 330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.
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- Wheeler, Eleanor, et al.
(author)
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Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis
- 2017
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In: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
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Journal article (peer-reviewed)abstract
- Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
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