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Effects of early probiotic supplementation in a pediatric setting: Focus on body composition, metabolism and inflammation
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

We aimed to determine the short- and long-term effects on growth, body composition, metabolic and inflammatory markers following supplementation with the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) during weaning. Methods: One-hundred and seventy-nine healthy, infants in Umeå city, Västerbotten County were randomised to daily intake of cereals with (n=89) or without (n=90) LF19 108 colony-forming units from 4 to 13 months of age. Weight, length, head circumference and body composition, assessed by skinfold thickness, were examined at 4, 5.5, 6.5, 9, 12 and 13 months of age. Venous blood was drawn at 5.5 and 13 months. In all, 171 infants completed the intervention and were invited to a follow-up at 8-9 years of age between 2009 and 2011, 120 children participated. Weight, height, sagittal abdominal diameter and body composition (using Dual Energy X-ray Absorptiometry-scan) were measured. Data on weight and height at 4 years were collected from medical records. The families filled out a 4-day food record and a food frequency questionnaire, physical activity was assessed using a pedometer for 7 days. At 5.5, 13 months and 8-9 years of age we analysed the serum blood lipid profile. At 8-9 years fasting glucose, insulin, aspartate and alanine transaminases were analysed in serum. Homeostatic Model Assessment index was calculated. At follow-up serum adiponectin, high-sensitivity C-reactive protein and plasma C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide 1, glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin were analysed. For characterisation of the plasma metabolome, a subgroup (n=40) was analysed at 5.5 and 13 months of age by gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) analysis and in all (n=112) children at the follow-up using untargeted GC-GC/MS. Results: There were no differences between the LF19 and placebo group regarding body weight, length/height at any assessment from 4 months to 8-9 years of age; nor were there any differences between the groups in body composition. In the LF19 group 19 % were overweight/obese, the corresponding number was 21 % in the placebo group (p=0.78). Analysed metabolic and inflammatory markers, both during the intervention and the follow-up did not differ between the two groups. At 13 months of age lower levels of palmitic acid and palmitoleic acid (both p<0.04) and higher levels of putrescine (p<0.01) were seen in the LF19 compared to the placebo group. These differences did not persist at 8-9 years of age. At that age, we found statistically stronger models when comparing overweight/obese and normal weight children as well as in relation to sex. Conclusion: Early intervention with the probiotic LF19 at the time of weaning exerted transient effects on the metabolome. In a long-term perspective, we found neither benefit nor harm on growth, body composition, metabolic or inflammatory markers following supplementation with LF19 during weaning.

Place, publisher, year, edition, pages
Umeå: Umeå universitet , 2016. , 71 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1785
Keyword [en]
Lactobacillus paracasei ssp. paracasei F19, infants, children, growth, body composition, metabolism, follow-up
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
URN: urn:nbn:se:umu:diva-119835ISBN: 978-91-7601-425-7 (print)OAI: oai:DiVA.org:umu-119835DiVA: diva2:924749
Public defence
2016-05-20, Sal E04, målpunkt R-1 (by 6E), Biomedicin, Norrlands universitetssjukhus, Umeå, 13:00 (English)
Opponent
Supervisors
Available from: 2016-04-29 Created: 2016-04-28 Last updated: 2016-04-29Bibliographically approved
List of papers
1. Impact of probiotic feeding during weaning on the serum lipid profile and plasma metabolome in infants
Open this publication in new window or tab >>Impact of probiotic feeding during weaning on the serum lipid profile and plasma metabolome in infants
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2013 (English)In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 110, no 1, 116-126 p.Article in journal (Refereed) Published
Abstract [en]

The gut microbiome interacts with the host in the metabolic response to diet, and early microbial aberrancies may be linked to the development of obesity and metabolic disorders later in life. Probiotics have been proposed to affect metabolic programming and blood lipid levels, although studies are lacking in infants. Here, we report on the lipid profile and global metabolic response following daily feeding of probiotics during weaning. A total of 179 healthy, term infants were randomised to daily intake of cereals with (n 89) or without (n 90) the addition of Lactobacillus paracasei ssp. paracasei F19 (LF19) 108 colony-forming units per serving from 4 to 13 months of age. Weight, length and skinfold thickness were monitored. Venous blood was drawn at 5·5 and 13 months of age for analysis of the serum lipid profile. In a subsample, randomly selected from each group, GC-time-of-flight/MS was used to metabolically characterise plasma samples from thirty-seven infants. A combination of multi- and univariate analysis was applied to reveal differences related to LF19 treatment based on 228 putative metabolites, of which ninety-nine were identified or classified. We observed no effects of probiotic feeding on anthropometrics or the serum lipid profile. However, we detected significantly lower levels of palmitoleic acid (16 : 1) (P < 0·05) and significantly higher levels of putrescine (P < 0·01) in LF19-treated infants. Palmitoleic acid is a major MUFA strongly linked to visceral obesity, while putrescine is a polyamine with importance for gut integrity. Whether the observed differences will have long-term health consequences are being followed.

Place, publisher, year, edition, pages
Cambridge University Press, 2013
Keyword
Probiotics, Lactobacillus paracaseissp.paracasei strain F19, Metabolomics, Infant feeding
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-62208 (URN)10.1017/S0007114512004618 (DOI)000320123500013 ()23228571 (PubMedID)
Available from: 2012-12-12 Created: 2012-12-12 Last updated: 2017-12-07Bibliographically approved
2. Probiotics during weaning: a follow-up study on effects on body composition and metabolic markers at school age
Open this publication in new window or tab >>Probiotics during weaning: a follow-up study on effects on body composition and metabolic markers at school age
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2015 (English)In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 54, no 3, 355-363 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: An aberrant gut microbiome has been suggested to contribute to the worldwide epidemic of obesity. In animal models, the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) induced upregulation of genes involved in energy homoeostasis, reduced body fat and altered the serum (S) lipoprotein profile. In our previous report, feeding LF19 to infants during weaning impacted the global plasma metabolome. LF19 lowered palmitoleic acid, a monounsaturated fatty acid associated with hypertriglyceridemia and increased visceral adiposity. Therefore, we assessed if feeding LF19 from 4 to 13 months of age would have long-term effects on body composition, growth and metabolic markers.

METHODS: Of 179 children included in our baseline study, 120 entered the follow-up at 8-9 years of age, n = 58 in the probiotic and n = 62 in the placebo group. Body composition was measured using dual energy X-ray absorptiometry. Anthropometrics of the child and accompanying parent(s) were assessed. S-lipids, insulin, glucose and transaminases were determined after overnight fasting.

RESULTS: LF19 did not affect body mass index z-score, sagittal abdominal diameter, fat-free mass, fat mass index, truncal fat %, android or gynoid fat % and had no long-term impact on any of the assessed metabolic markers (p > 0.05).

CONCLUSION: Feeding LF19 during infancy did not modulate body composition, growth or any of the assessed metabolic markers at school age. The steady increase in probiotic products targeting infants and children calls for long-term follow-up of initiated probiotic intervention studies.

Keyword
Probiotic, Lactobacillus paracasei ssp paracasei F19, Overweight, Long-term effects, Children
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-101467 (URN)10.1007/s00394-014-0715-y (DOI)000351513000003 ()24830782 (PubMedID)
Available from: 2015-03-31 Created: 2015-03-31 Last updated: 2017-12-04Bibliographically approved
3. Impact of probiotics during weaning on the metabolic and inflammatory profile: follow-up at school age
Open this publication in new window or tab >>Impact of probiotics during weaning on the metabolic and inflammatory profile: follow-up at school age
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2015 (English)In: International Journal of Food Sciences and Nutrition, ISSN 0963-7486, E-ISSN 1465-3478, Vol. 66, no 6, 686-691 p.Article in journal (Refereed) Published
Abstract [en]

We hypothesised that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) (dep. nr LMG P-17806) during weaning would program the metabolic and inflammatory profile and studied its association with previously assessed body composition. In a double-blind, placebo-controlled trial, 179 infants were randomised to daily feeding of cereals with or without LF19 10 8 CFU from 4 to 13 months of age. At age 8-9 years, 120 children were reassessed. Using high-sensitivity multiplex immunoassay technology and ELISA, we found that overweight/obese children had increased plasma C-peptide, plasminogen activator inhibitor-1, leptin and serum high-sensitivity C-reactive protein (hsCRP) after overnight fasting compared with normal weight children, independently of LF19. After excluding the obese, leptin and hsCRP were still increased, revealing an aberrant metabolic and inflammatory state already in overweight, pre-pubertal children. Higher body mass index z-score, sagittal abdominal diameter, truncal and total body fat % were associated with an aberrant metabolic and inflammatory profile, emphasising the need for early prevention strategies although no programming effect of LF19 was observed.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2015
Keyword
body composition, children, inflammation, Lactobacillus paracasei ssp paracasei F19, metabolism, crobiota
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-109965 (URN)10.3109/09637486.2015.1025717 (DOI)000361335300012 ()
Available from: 2015-10-09 Created: 2015-10-09 Last updated: 2017-12-01Bibliographically approved
4. The plasma metabolome is influenced by body weight and sex already at school age
Open this publication in new window or tab >>The plasma metabolome is influenced by body weight and sex already at school age
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Diet is one of the determinants of gut microbial composition. Reported changes in the biodiversity of the gut microbiota in the obese have spurred interest in gut microbiota modulation by dietary interventions. Using an untargeted metabolomics approach, we previously reported that infant cereals with the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) fed daily from 4 to 13 months of age affected the plasma metabolome with lower levels of fatty acids associated with obesity indices compared with placebo. The study participants were invited to a follow-up study at 8-9 years of age and 120 children participated. Venous blood was drawn after overnight fasting and plasma samples were available from 112 children. Samples were analysed using GCxGC-time-of-flight/MS for characterisation of the global plasma metabolome. A combination of multivariate and univariate analysis was used to reveal differences between the LF19 and placebo group, and according to weight class and sex. The lower levels of palmitic acid and palmitoleic acid in the LF19 group during the intervention did not remain at the follow-up. Stronger models according to weight class and sex were obtained. BMI was associated with several metabolites including the branched-chain amino acids leucine and isoleucine, and the aromatic amino acids, tyrosine and phenylalanine. Collectively, feeding LF19 during weaning induced transient effects on the plasma metabolome. The disparities seen in the metabolic profile of overweight/obese young school children underscore the need for effective early preventive and treatment strategies.

Keyword
pediatrics, probiotics, Lactobacillus paracasei ssp paracasei F19, long-term follow-up, metabolomics
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
urn:nbn:se:umu:diva-119834 (URN)
Available from: 2016-04-28 Created: 2016-04-28 Last updated: 2016-04-29Bibliographically approved

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