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Wang HZ, Hayles EH, Fiander M, Sinn JK, Osborn DA. Probiotics in infants for prevention of allergic disease. Cochrane Database Syst Rev 2025; 6:CD006475. [PMID: 40511642 PMCID: PMC12163975 DOI: 10.1002/14651858.cd006475.pub3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/16/2025]
Abstract
RATIONALE This is an update of a Cochrane review first published in 2007. Allergic disease and food allergy are prevalent, and contribute to a significant burden of disease on the individual, their family and the healthcare system. Probiotics are live bacteria that colonise the gastrointestinal tract, and have been studied in many clinical trials for preventing allergic conditions. OBJECTIVES To evaluate the benefits and harms of a probiotic, or a probiotic with added prebiotic ('synbiotic'), compared with control (placebo or no treatment) for preventing allergic diseases (asthma, eczema, allergic rhinitis) and dietary allergies in infants by two years of age. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase and trial registries in December 2023. We reviewed the reference lists of studies selected for inclusion in this review, and systematic reviews on similar topics. We manually searched conference abstracts. ELIGIBILITY CRITERIA We included randomised controlled trials that compared a probiotic to a control, or a probiotic added to a prebiotic ('synbiotic'). We included enterally fed infants in the first six months of life without clinical evidence of allergic disease. We included probiotics added to human milk or infant formula, added in the manufacturing process or given separately. OUTCOMES Infant incidence by two years of age and childhood incidence (up to 10 years of age or up to the age of latest report between 2 and 10 years) of specific allergic diseases, including: asthma, eczema, allergic rhinitis, immunoglobulin E (IgE)-mediated food allergy, IgE-mediated cow's milk protein allergy. Events of anaphylaxis and potential harms including adverse effects, harms or infection with probiotic bacteria. RISK OF BIAS We used the Cochrane RoB 2 tool to assess bias in the studies. SYNTHESIS METHODS We used the random-effects (Mantel-Haenszel) model for meta-analysis where possible. Where this was not possible due to the nature of the data, we synthesised and interpreted individual studies separately. We used GRADE to assess the certainty of evidence for each outcome. INCLUDED STUDIES We included 24 studies (7077 mother-infant pairs). The studies were conducted in many parts of the world, including the USA, Europe, South Korea, Japan, Singapore and Australia, with most being conducted in Europe. Studies were published between 2001 and 2020. As some studies measured outcomes such as eczema using different criteria, we made assumptions to allow us to combine data. SYNTHESIS OF RESULTS Probiotics may result in little to no difference in asthma (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.65 to 1.44; 4 studies, 954 participants; low-certainty evidence), allergic rhinitis (RR 0.89, 95% CI 0.45 to 1.77; 5 studies, 1045 participants; low-certainty evidence) and IgE-mediated cow's milk protein allergy (RR 0.99, 95% CI 0.82 to 1.20; 4 studies, 259 participants; low-certainty evidence) by two years of age. Probiotics may result in a slight reduction in eczema by two years of age (RR 0.87, 95% CI 0.78 to 0.97; 18 studies, 3494 participants; low-certainty evidence); however, sensitivity analysis of the studies at low risk of bias showed little or no difference in eczema by two years of age (RR 0.86, 95% CI 0.69 to 1.07; 4 studies, 892 participants). Probiotic supplementation may have little to no effect on the incidence of food allergy by two years, but the evidence is very uncertain (RR 1.12, 95% CI 0.57 to 2.20; 3 studies, 857 participants; very low-certainty evidence). The evidence is very uncertain about the effect of synbiotics on eczema by two years of age (RR 0.88, 95% CI 0.52 to 1.47; 3 studies, 1235 participants; very low-certainty evidence). Synbiotics may result in little to no difference in food allergy by two years of age (RR 1.06, 95% CI 0.55 to 2.07; 1 study, 223 participants; low-certainty evidence). There were no data for the effect of synbiotics on asthma, allergic rhinitis and IgE-mediated cow's milk protein allergy by two years of age. Probiotic or synbiotic supplementation may result in little to no difference in potential harms including adverse effects, harms or infection with probiotic bacteria at any point during the study intervention by two years of age. There were no serious adverse events related to probiotics or synbiotics reported. We had some concerns about risk of bias for most studies, with only a few judged at low risk of bias. Some studies had a high risk of bias due to unclear randomisation, missing data and lack of prespecified intentions. Estimates were often imprecise, with wide CIs due to limited events. The limited data prevented subgroup analyses on infant risk factors and feeding methods for outcomes other than the effect of probiotics on eczema. Only three studies assessed synbiotic supplementation, leaving their role in allergic disease prevention uncertain. The included studies were mainly in high-income countries in many different areas of the world, but may have limited applicability to other regions. AUTHORS' CONCLUSIONS There is insufficient evidence to make conclusions about the effect of probiotics and synbiotics on preventing the development of allergic diseases by two years of age and during childhood up to 10 years of age. Although there were no serious adverse events reported for the use of probiotics in infants, incorporating probiotics and synbiotics into routine practice requires further information to support their use. FUNDING This Cochrane review had no dedicated funding. REGISTRATION Protocol (2007) available via https://doi.org/10.1002/14651858.CD006475. Original review (2007) available via https://doi.org/10.1002/14651858.CD006475.pub2.
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Affiliation(s)
- Hang Zhen Wang
- Macquarie Medical School, Macquarie University, Sydney, Australia
| | - Elizabeth H Hayles
- Department of Neonatology, Royal North Shore Hospital, The University of Sydney, St Leonards, Australia
| | | | - John Kh Sinn
- Department of Neonatology, Royal North Shore Hospital, Sydney, Australia
- Faculty of Medicine and Health Sciences, Macquarie University, Macquarie University, Sydney, Australia
| | - David A Osborn
- Central Clinical School, School of Medicine, The University of Sydney, Sydney, Australia
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Poulsen CE, Vinding R, Rasmussen MA, Shah S, Trivedi U, Rodriguez CL, Widdowson ML, Jiang J, Poulsen CS, Eliasen A, Chawes B, Bønnelykke K, Hansen CHF, Sørensen SJ, Thorsen J, Stokholm J. No association between the early-life gut microbiota and childhood body mass index and body composition. MED 2025; 6:100538. [PMID: 39536756 DOI: 10.1016/j.medj.2024.10.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 03/12/2024] [Accepted: 10/15/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND The gut microbiota has been implicated in adult obesity, but the causality is still unclear. It has been hypothesized that an obesity-prone gut microbiota can be established in infancy, but only few studies have examined the early-life gut microbiota in relation to obesity in childhood, and no consistent associations have been reported. Here, we examine the association between the early-life gut microbiota and body mass index (BMI) development and body composition throughout childhood. METHODS Gut microbiota from stool were collected from 700 children in the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort at ages of 1 week, 1month, 1 year, 4 years, and 6 years and analyzed by 16S rRNA gene sequencing. Outcomes included BMI World Health Organization (WHO) Z scores (zBMI), overweight (zBMI > 1.04) and obesity (zBMI > 1.64) (0-10 years), and adiposity rebound and body composition from dual-energy X-ray absorptiometry at 6 years. FINDINGS The early-life gut microbiota diversity, overall composition, and individual taxon abundances in unsupervised and supervised models were not consistently associated with either current or later BMI Z scores, overweight, obesity, adiposity rebound, or body composition in childhood. CONCLUSIONS In a deeply characterized longitudinal birth cohort, we did not observe any consistent associations between the early-life gut microbiota and BMI or risk of obesity in later childhood. While this does not conclusively rule out a relationship, it suggests that if such associations exist, they may be more complex and potentially influenced by factors emerging later in life, including lifestyle changes. FUNDING COPSAC is funded by private and public research funds (all listed on www.copsac.com).
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Affiliation(s)
- Christina Egeø Poulsen
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Rebecca Vinding
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Morten A Rasmussen
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Food Science, University of Copenhagen, 1958 Frederiksberg C, Denmark
| | - Shiraz Shah
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Urvish Trivedi
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Cristina Leal Rodriguez
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Michael L Widdowson
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Jie Jiang
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Casper S Poulsen
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Anders Eliasen
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Bio and Health Informatics, Technical University of Denmark, Kongens Lyngby, Denmark
| | - Bo Chawes
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Klaus Bønnelykke
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Camilla H F Hansen
- Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg C, Denmark
| | - Søren J Sørensen
- Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Jonathan Thorsen
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Jakob Stokholm
- Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Food Science, University of Copenhagen, 1958 Frederiksberg C, Denmark.
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Gutierrez MW, van Tilburg Bernardes E, Ren E, Kalbfleisch KN, Day M, Lameu EL, Glatthardt T, Mercer EM, Sharma S, Zhang H, Al-Azawy A, Chleilat F, Hirota SA, Reimer RA, Arrieta MC. Early-life gut mycobiome core species modulate metabolic health in mice. Nat Commun 2025; 16:1467. [PMID: 39922818 PMCID: PMC11807121 DOI: 10.1038/s41467-025-56743-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Accepted: 01/27/2025] [Indexed: 02/10/2025] Open
Abstract
The gut microbiome causally contributes to obesity; however, the role of fungi remains understudied. We previously identified three core species of the infant gut mycobiome (Rhodotorula mucilaginosa, Malassezia restricta and Candida albicans) that correlated with body mass index, however their causal contributions to obesity development are unknown. Here we show the effects of early-life colonization by these fungal species on metabolic health in gnotobiotic mice fed standard (SD) or high-fat-high-sucrose (HFHS) diets. Each species resulted in bacterial microbiome compositional and functional differences. R. mucilaginosa and M. restricta increased adiposity in mice fed SD, while only R. mucilaginosa exacerbated metabolic disease. In contrast, C. albicans resulted in leanness and resistance to diet-induced obesity. Intestinal nutrient transporter expression was unaffected by the presence of fungi in jejunal enteroids, yet the immune landscape in white adipose tissue was distinctly impacted by each fungal species, suggesting that these phenotypes may be a result of fungal immune regulation. This work revealed that three common fungal colonizers have distinct causal influences on obesity and metabolic inflammation and justifies the consideration of fungi in microbiome research on host metabolism.
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Affiliation(s)
- Mackenzie W Gutierrez
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada
- International Microbiome Centre, Snyder Institute, University of Calgary, Calgary, AB, Canada
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Erik van Tilburg Bernardes
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada
- International Microbiome Centre, Snyder Institute, University of Calgary, Calgary, AB, Canada
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Ellen Ren
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada
- International Microbiome Centre, Snyder Institute, University of Calgary, Calgary, AB, Canada
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Kristen N Kalbfleisch
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada
- International Microbiome Centre, Snyder Institute, University of Calgary, Calgary, AB, Canada
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Madeline Day
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada
- International Microbiome Centre, Snyder Institute, University of Calgary, Calgary, AB, Canada
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Ewandson Luiz Lameu
- International Microbiome Centre, Snyder Institute, University of Calgary, Calgary, AB, Canada
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Thaís Glatthardt
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada
- International Microbiome Centre, Snyder Institute, University of Calgary, Calgary, AB, Canada
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Emily M Mercer
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada
- International Microbiome Centre, Snyder Institute, University of Calgary, Calgary, AB, Canada
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Sunita Sharma
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada
- International Microbiome Centre, Snyder Institute, University of Calgary, Calgary, AB, Canada
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Hong Zhang
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Ali Al-Azawy
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada
- International Microbiome Centre, Snyder Institute, University of Calgary, Calgary, AB, Canada
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Faye Chleilat
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada
- Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA
| | - Simon A Hirota
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada
| | - Raylene A Reimer
- International Microbiome Centre, Snyder Institute, University of Calgary, Calgary, AB, Canada
- Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada
- Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada
| | - Marie-Claire Arrieta
- Department of Pediatrics, University of Calgary, Calgary, AB, Canada.
- Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
- International Microbiome Centre, Snyder Institute, University of Calgary, Calgary, AB, Canada.
- Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada.
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Lammi C, Ottaviano E, Fiore G, Bollati C, d'Adduzio L, Fanzaga M, Ceccarani C, Vizzuso S, Zuccotti G, Borghi E, Verduci E. Effect of docosahexaenoic acid as an anti-inflammatory for Caco-2 cells and modulating agent for gut microbiota in children with obesity (the DAMOCLE study). J Endocrinol Invest 2025; 48:465-481. [PMID: 39186221 PMCID: PMC11785711 DOI: 10.1007/s40618-024-02444-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Accepted: 08/12/2024] [Indexed: 08/27/2024]
Abstract
PURPOSE Docosahexaenoic acid (DHA) is a long-chain omega-3 polyunsaturated fatty acid. We investigated the dual health ability of DHA to modulate gut microbiota in children with obesity and to exert anti-inflammatory activity on human intestinal Caco-2 cells. METHODS In a pilot study involving 18 obese children (8-14 years), participants received a daily DHA supplement (500 mg/day) and dietary intervention from baseline (T0) to 4 months (T1), followed by dietary intervention alone from 4 months (T1) to 8 months (T2). Fecal samples, anthropometry, biochemicals and dietary assessment were collected at each timepoint. At preclinical level, we evaluated DHA's antioxidant and anti-inflammatory effects on Caco-2 cells stimulated with Hydrogen peroxide (H2O2) and Lipopolysaccharides (LPS), by measuring also Inducible nitric oxide synthase (iNOS) levels and cytokines, respectively. RESULTS Ten children were included in final analysis. No major changes were observed for anthropometric and biochemical parameters, and participants showed a low dietary compliance at T1 and T2. DHA supplementation restored the Firmicutes/Bacteroidetes ratio that was conserved also after the DHA discontinuation at T2. DHA supplementation drove a depletion in Ruminococcaceae and Dialisteraceae, and enrichment in Bacteroidaceae, Oscillospiraceae, and Akkermansiaceae. At genus level, Allisonella was the most decreased by DHA supplementation. In Caco-2 cells, DHA decreased H2O2-induced reactive oxygen species (ROS) and nitric oxide (NO) production via iNOS pathway modulation. Additionally, DHA modulated proinflammatory (IL-1β, IL-6, IFN-γ, TNF-α) and anti-inflammatory (IL-10) cytokine production in LPS-stimulated Caco-2 cells. CONCLUSION An improvement in gut dysbiosis of children with obesity seems to be triggered by DHA and to continue after discontinuation. The ability to modulate gut microbiota, matches also with an anti-inflammatory effect of DHA on Caco-2 cells.
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Affiliation(s)
- C Lammi
- Department of Pharmaceutical Sciences, University of Milan, 20133, Milan, Italy
| | - E Ottaviano
- Department of Health Sciences, University of Milan, 20142, Milan, Italy
| | - G Fiore
- Department of Health Sciences, University of Milan, 20142, Milan, Italy.
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Via Lodovico Castelvetro 32, 20154, Milan, Italy.
| | - C Bollati
- Department of Pharmaceutical Sciences, University of Milan, 20133, Milan, Italy
| | - L d'Adduzio
- Department of Pharmaceutical Sciences, University of Milan, 20133, Milan, Italy
| | - M Fanzaga
- Department of Pharmaceutical Sciences, University of Milan, 20133, Milan, Italy
| | - C Ceccarani
- Institute for Biomedical Technologies, CNR, Segrate, Italy
| | - S Vizzuso
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Via Lodovico Castelvetro 32, 20154, Milan, Italy
| | - G Zuccotti
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Via Lodovico Castelvetro 32, 20154, Milan, Italy
- Department of Biomedical and Clinical Sciences, University of Milan, 20157, Milan, Italy
| | - E Borghi
- Department of Health Sciences, University of Milan, 20142, Milan, Italy
| | - E Verduci
- Department of Health Sciences, University of Milan, 20142, Milan, Italy
- Metabolic Diseases Unit, Department of Paediatrics, Vittore Buzzi Children's Hospital, University of Milan, 20157, Milan, Italy
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Papetti L, Del Chierico F, Frattale I, Toto F, Scanu M, Mortera SL, Rapisarda F, Di Michele M, Monte G, Ursitti F, Sforza G, Putignani L, Valeriani M. Pediatric migraine is characterized by traits of ecological and metabolic dysbiosis and inflammation. J Headache Pain 2024; 25:171. [PMID: 39379796 PMCID: PMC11462686 DOI: 10.1186/s10194-024-01871-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 09/19/2024] [Indexed: 10/10/2024] Open
Abstract
BACKGROUND Recently, there has been increasing interest in the possible role of the gut microbiota (GM) in the onset of migraine. Our aim was to verify whether bacterial populations associated with intestinal dysbiosis are found in pediatric patients with migraine. We looked for which metabolic pathways, these bacteria were involved and whether they might be associated with gut inflammation and increased intestinal permeability. METHODS Patients aged between 6 and 17 years were recruited. The GM profiling was performed by the 16S rRNA metataxonomics of faecal samples from 98 patients with migraine and 98 healthy subjects. Alpha and beta diversity analyses and multivariate and univariate analyses were applied to compare the gut microbiota profiles between the two group. To predict functional metabolic pathways, we used phylogenetic analysis of communities. The level of indican in urine was analyzed to investigate the presence of metabolic dysbiosis. To assess gut inflammation, increased intestinal permeability and the mucosal immune activation, we measured the plasmatic levels of lipopolysaccharide, occludin and IgA, respectively. RESULTS The α-diversity analysis revealed a significant increase of bacterial richness in the migraine group. The β-diversity analysis showed significant differences between the two groups indicating gut dysbiosis in patients with migraine. Thirty-seven metabolic pathways were increased in the migraine group, which includes changes in tryptophan and phenylalanine metabolism. The presence of metabolic dysbiosis was confirmed by the increased level of indican in urine. Increased levels of plasmatic occludin and IgA indicated the presence of intestinal permeability and mucosal immune activation. The plasmatic LPS levels showed a low intestinal inflammation in patients with migraine. CONCLUSIONS Pediatric patients with migraine present GM profiles different from healthy subjects, associated with metabolic pathways important in migraine.
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Affiliation(s)
- Laura Papetti
- Developmental Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio, 4, Rome, Italy
| | - Federica Del Chierico
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Microbiome, Bambino Gesù Children's Hospital, IRCCS, Viale Di San Paolo, 15, Rome, Italy.
| | - Ilaria Frattale
- Child Neurology and Psychiatry Unit, Department of Wellbeing of Mental and Neurological, Dental and Sensory Organ Health, Policlinico Tor Vergata Foundation Hospital, Rome, Italy
| | - Francesca Toto
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Microbiome, Bambino Gesù Children's Hospital, IRCCS, Viale Di San Paolo, 15, Rome, Italy
| | - Matteo Scanu
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Microbiome, Bambino Gesù Children's Hospital, IRCCS, Viale Di San Paolo, 15, Rome, Italy
| | - Stefano Levi Mortera
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Microbiome, Bambino Gesù Children's Hospital, IRCCS, Viale Di San Paolo, 15, Rome, Italy
| | - Federica Rapisarda
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Microbiome, Bambino Gesù Children's Hospital, IRCCS, Viale Di San Paolo, 15, Rome, Italy
| | - Marta Di Michele
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Microbiome, Bambino Gesù Children's Hospital, IRCCS, Viale Di San Paolo, 15, Rome, Italy
| | - Gabriele Monte
- Developmental Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio, 4, Rome, Italy
| | - Fabiana Ursitti
- Developmental Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio, 4, Rome, Italy
| | - Giorgia Sforza
- Developmental Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio, 4, Rome, Italy
| | - Lorenza Putignani
- Unit of Microbiology and Diagnostic Immunology, Unit of Microbiomics and Research Area of Immunology, Rheumatology and Infectious Diseases, Unit of Microbiome, Bambino Gesù Children's Hospital, IRCCS, Viale Di San Paolo, 15, Rome, Italy.
| | - Massimiliano Valeriani
- Developmental Neurology Unit, Bambino Gesù Children's Hospital, IRCCS, Piazza Sant'Onofrio, 4, Rome, Italy.
- Systems Medicine Department, Tor Vergata University of Rome, Rome, Italy.
- Center for Sensory-Motor Interaction, Aalborg University, Aalborg, Denmark.
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Yong GJM, Porsche CE, Sitarik AR, Fujimura KE, McCauley K, Nguyen DT, Levin AM, Woodcroft KJ, Ownby DR, Rundle AG, Johnson CC, Cassidy-Bushrow A, Lynch SV. Precocious infant fecal microbiome promotes enterocyte barrier dysfuction, altered neuroendocrine signaling and associates with increased childhood obesity risk. Gut Microbes 2024; 16:2290661. [PMID: 38117587 PMCID: PMC10761186 DOI: 10.1080/19490976.2023.2290661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Accepted: 11/29/2023] [Indexed: 12/22/2023] Open
Abstract
Early life gut microbiome composition has been correlated with childhood obesity, though microbial functional contributions to disease origins remain unclear. Here, using an infant birth cohort (n = 349) we identify a distinct fecal microbiota composition in 1-month-old infants with the lowest rate of exclusive breastfeeding, that relates with higher relative risk for obesity and overweight phenotypes at two years. Higher-risk infant fecal microbiomes exhibited accelerated taxonomic and functional maturation and broad-ranging metabolic reprogramming, including reduced concentrations of neuro-endocrine signals. In vitro, exposure of enterocytes to fecal extracts from higher-risk infants led to upregulation of genes associated with obesity and with expansion of nutrient sensing enteroendocrine progenitor cells. Fecal extracts from higher-risk infants also promoted enterocyte barrier dysfunction. These data implicate dysregulation of infant microbiome functional development, and more specifically promotion of enteroendocrine signaling and epithelial barrier impairment in the early-life developmental origins of childhood obesity.
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Affiliation(s)
- Germaine J. M. Yong
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
- Asian Microbiome Library Pte Ltd, Singapore and Singapore Institute of Food and Biotechnology Innovation, Singapore, Singapore
| | - Cara E. Porsche
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Alexandra R. Sitarik
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | - Kei E. Fujimura
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
- Genetic Disease Laboratory, California Department of Public Health, San Francisco, CA, USA
| | - Kathryn McCauley
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Dat T. Nguyen
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
- Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Albert M. Levin
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | | | - Dennis R. Ownby
- Division of Allergy and Clinical Immunology, Department of Pediatrics, Augusta University, Augusta, GA, USA
| | - Andrew G. Rundle
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Christine C. Johnson
- Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA
| | | | - Susan V. Lynch
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
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Ren J, Li H, Zeng G, Pang B, Wang Q, Wei J. Gut microbiome-mediated mechanisms in aging-related diseases: are probiotics ready for prime time? Front Pharmacol 2023; 14:1178596. [PMID: 37324466 PMCID: PMC10267478 DOI: 10.3389/fphar.2023.1178596] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2023] [Accepted: 05/24/2023] [Indexed: 06/17/2023] Open
Abstract
Chronic low-grade inflammation affects health and is associated with aging and age-related diseases. Dysregulation of the gut flora is an important trigger for chronic low-grade inflammation. Changes in the composition of the gut flora and exposure to related metabolites have an effect on the inflammatory system of the host. This results in the development of crosstalk between the gut barrier and immune system, contributing to chronic low-grade inflammation and impairment of health. Probiotics can increase the diversity of gut microbiota, protect the gut barrier, and regulate gut immunity, thereby reducing inflammation. Therefore, the use of probiotics is a promising strategy for the beneficial immunomodulation and protection of the gut barrier through gut microbiota. These processes might positively influence inflammatory diseases, which are common in the elderly.
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Affiliation(s)
- Jing Ren
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Huimin Li
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Guixing Zeng
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Boxian Pang
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Qiuhong Wang
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Junping Wei
- Department of Endocrinology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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8
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Xiao L, Zhao F. Microbial transmission, colonisation and succession: from pregnancy to infancy. Gut 2023; 72:772-786. [PMID: 36720630 PMCID: PMC10086306 DOI: 10.1136/gutjnl-2022-328970] [Citation(s) in RCA: 66] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Accepted: 01/10/2023] [Indexed: 02/02/2023]
Abstract
The microbiome has been proven to be associated with many diseases and has been used as a biomarker and target in disease prevention and intervention. Currently, the vital role of the microbiome in pregnant women and newborns is increasingly emphasised. In this review, we discuss the interplay of the microbiome and the corresponding immune mechanism between mothers and their offspring during the perinatal period. We aim to present a comprehensive picture of microbial transmission and potential immune imprinting before and after delivery. In addition, we discuss the possibility of in utero microbial colonisation during pregnancy, which has been highly debated in recent studies, and highlight the importance of the microbiome in infant development during the first 3 years of life. This holistic view of the role of the microbial interplay between mothers and infants will refine our current understanding of pregnancy complications as well as diseases in early life and will greatly facilitate the microbiome-based prenatal diagnosis and treatment of mother-infant-related diseases.
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Affiliation(s)
- Liwen Xiao
- Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Fangqing Zhao
- Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
- Key Laboratory of System Biology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, China
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Fiore G, Magenes VC, DI Profio E, Milanta C, Calcaterra V, Diamanti A, Campoy C, Zuccotti G, Verduci E. Gut microbiota in obesity and related comorbidities in children and adolescents: the role of biotics in treatment. Minerva Pediatr (Torino) 2022; 74:632-649. [PMID: 35708037 DOI: 10.23736/s2724-5276.22.06964-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
INTRODUCTION Obesity is a complex pathology, globally spread, with a multifactorial pathogenesis, strictly linked with lifestyle, hormones, genetic and epigenetic factors. Evidence supports that obesity, and its comorbidities, are related to changes in gut microbiota, partially responsible of the modulation of energy metabolism. EVIDENCE ACQUISITION Pediatric obesity has been associated with lower bacterial diversity and differences in composition of the gut microbiota, also varying according to the metabolic status of obese subjects. Indeed, differences in distributions and activity of microorganisms in the gut of metabolically healthy and unhealthy obese children have been highlighted. EVIDENCE SYNTHESIS Based on human studies, this review aims to discuss gut microbiota alterations in obese children and adolescents and its role in obese-related complications. Moreover, the role of biotics (probiotics, prebiotics, synbiotics and -marginally- postbiotics) has been analyzed as modulator of obesity-related dysbiosis. CONCLUSIONS As a conclusion, a deeper knowledge about biotic mechanisms of action would be of great interest to implement the clinical care of children and adolescents with obesity and related comorbidities.
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Affiliation(s)
- Giulia Fiore
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Vittoria C Magenes
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Elisabetta DI Profio
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Chiara Milanta
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy
| | - Valeria Calcaterra
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy
- Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, Pavia, Italy
| | - Antonella Diamanti
- Unit of Hepatology Gastroenterology and Nutrition, Bambino Gesù Children's Hospital, Rome, Italy
| | - Cristina Campoy
- Centre of Excellence for Pediatric Research EURISTIKOS, Department of Pediatrics, University of Granada, Granada, Spain
| | - Gianvincenzo Zuccotti
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy
- L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy
- Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, University of Milan, Milan, Italy
| | - Elvira Verduci
- Department of Pediatrics, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy -
- Department of Health Sciences, University of Milan, Milan, Italy
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10
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Exploring the Potential of Human Milk and Formula Milk on Infants’ Gut and Health. Nutrients 2022; 14:nu14173554. [PMID: 36079814 PMCID: PMC9460722 DOI: 10.3390/nu14173554] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 08/25/2022] [Accepted: 08/26/2022] [Indexed: 11/21/2022] Open
Abstract
Early-life gut microbiota plays a role in determining the health and risk of developing diseases in later life. Various perinatal factors have been shown to contribute to the development and establishment of infant gut microbiota. One of the important factors influencing the infant gut microbial colonization and composition is the mode of infant feeding. While infant formula milk has been designed to resemble human milk as much as possible, the gut microbiome of infants who receive formula milk differs from that of infants who are fed human milk. A diverse microbial population in human milk and the microbes seed the infant gut microbiome. Human milk contains nutritional components that promote infant growth and bioactive components, such as human milk oligosaccharides, lactoferrin, and immunoglobulins, which contribute to immunological development. In an attempt to encourage the formation of a healthy gut microbiome comparable to that of a breastfed infant, manufacturers often supplement infant formula with prebiotics or probiotics, which are known to have a bifidogenic effect and can modulate the immune system. This review aims to elucidate the roles of human milk and formula milk on infants’ gut and health.
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11
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Huang Q, Cai G, Liu T, Liu Z. Relationships Among Gut Microbiota, Ischemic Stroke and Its Risk Factors: Based on Research Evidence. Int J Gen Med 2022; 15:2003-2023. [PMID: 35795301 PMCID: PMC9252587 DOI: 10.2147/ijgm.s353276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 02/08/2022] [Indexed: 11/27/2022] Open
Abstract
Stroke is a highly lethal disease and disabling illness while ischemic stroke accounts for the majority of stroke. It has been found that inflammation plays a key role in the initiation and progression of stroke, and atherosclerotic plaque rupture is considered to be the leading cause of ischemic stroke. Furthermore, chronic inflammatory diseases, such as obesity, type 2 diabetes mellitus (T2DM) and hypertension, are also considered as the high-risk factors for stroke. Recently, the topic on how gut microbiota affects human health has aroused great concern. The initiation and progression of ischemic stroke has been found to have close relation with gut microbiota dysbiosis. Hence, this manuscript briefly summarizes the roles of gut microbiota in ischemic stroke and its related risk factors, and the practicability of preventing and alleviating ischemic stroke by reconstructing gut microbiota.
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Affiliation(s)
- Qinhong Huang
- First Clinical School, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China
| | - Guannan Cai
- First Clinical School, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China
| | - Ting Liu
- Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery, Innovation Center for Advanced Interdisciplinary Medicine, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, People’s Republic of China
- Correspondence: Ting Liu; Zhihua Liu, Email ;
| | - Zhihua Liu
- Department of Anorectal Surgery, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, People’s Republic of China
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12
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Gut Microbiota Diversity and Overweight/Obesity in Infancy: Results from a Nested Case-control Study. Curr Med Sci 2022; 42:210-216. [PMID: 34985609 DOI: 10.1007/s11596-021-2476-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Accepted: 03/09/2021] [Indexed: 11/03/2022]
Abstract
OBJECTIVE Childhood obesity is a major health concern worldwide. Previous studies have explored the relationship between obesity and gut microbiota. However, the results from such studies remain contradictory. METHODS In the present nested case-control study, based on a twin birth cohort study, the relationship between gut microbiota diversity and overweight/obesity in 1- and 6-month-old infants was explored. Twins were enrolled when one child had normal weight and the other child was overweight/obese at six months old. For both infants, stool samples were collected at 1 and 6 months of age. Finally, 12 twins were enrolled in the study. The gut microbiota was identified by 16S rRNA gene sequencing in the V3-V4 area. Six of the twins were monozygotic. RESULTS The results revealed that the microbiota communities of monozygotic twins were similar to those of dizygotic twins. The relative abundance (RA) of microbiota of 1-month-old twins was significantly higher than that of 6-month-old twins. However, the microbiota diversity of 1-month-old twins was significantly lower than that of 6-month-old twins. In addition, 6-month-old twins had significantly higher RA levels of Bifidobacterium and Lachnospiracea incertae sedis than 1-month-old twins. The 6-month-old group had significantly lower RA levels of Veillonella, Klebsiella, Akkermansia, Streptococcus, or Staphylococcus than the 1-month-old group. At six months, the RA level of Clostridium sensu stricto was higher in the overweight/obesity group than the normal-weight group. CONCLUSION These findings imply that changes in gut microbiota diversity during infancy may contribute to the development of obesity in early infancy.
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Hill L, Sharma R, Hart L, Popov J, Moshkovich M, Pai N. The neonatal microbiome in utero and beyond: perinatal influences and long-term impacts. J LAB MED 2021. [DOI: 10.1515/labmed-2021-0131] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Abstract
The neonatal microbiome offers a valuable model for studying the origins of human health and disease. As the field of metagenomics expands, we also increase our understanding of early life influences on its development. In this review we will describe common techniques used to define and measure the microbiome. We will review in utero influences, normal perinatal development, and known risk factors for abnormal neonatal microbiome development. Finally, we will summarize current evidence that links early life microbial impacts on the development of chronic inflammatory diseases, obesity, and atopy.
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Affiliation(s)
- Lee Hill
- Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition , McMaster Children’s Hospital, McMaster University , Hamilton , Canada
- Department of Human Biology, Division of Exercise Science and Sports Medicine , University of Cape Town , Cape Town , South Africa
| | - Ruchika Sharma
- Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition , McMaster Children’s Hospital, McMaster University , Hamilton , Canada
- McMaster University , Hamilton , Canada
| | - Lara Hart
- Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition , McMaster Children’s Hospital, McMaster University , Hamilton , Canada
| | - Jelena Popov
- Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition , McMaster Children’s Hospital, McMaster University , Hamilton , Canada
- University College Cork, College of Medicine and Health , Cork , Ireland
| | - Michal Moshkovich
- Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition , McMaster Children’s Hospital, McMaster University , Hamilton , Canada
- Faculty of Health Sciences , McMaster University , Hamilton , Canada
| | - Nikhil Pai
- Department of Paediatrics, Division of Gastroenterology, Hepatology and Nutrition , McMaster Children’s Hospital, McMaster University , Hamilton , Canada
- Farncombe Family Digestive Health Research Institute , McMaster University , Hamilton , Canada
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14
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The Intestinal Dysbiosis of Mothers with Gestational Diabetes Mellitus (GDM) and Its Impact on the Gut Microbiota of Their Newborns. THE CANADIAN JOURNAL OF INFECTIOUS DISEASES & MEDICAL MICROBIOLOGY = JOURNAL CANADIEN DES MALADIES INFECTIEUSES ET DE LA MICROBIOLOGIE MEDICALE 2021; 2021:3044534. [PMID: 34603565 PMCID: PMC8481071 DOI: 10.1155/2021/3044534] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 09/11/2021] [Indexed: 02/06/2023]
Abstract
Gestational diabetes mellitus (GDM) is defined as “diagnosed as impaired glucose tolerance for the first time during pregnancy,” which can lead to adverse pregnancy outcomes and produces divergent effects on mothers and newborns. In recent years, with the continuous expansion of obese people, GDM shows an upward trend. The abundant and diverse members of the human gut microbiota exert critical roles in the maintenance of human health. Studies have shown that GDM may be associated with disordered gut microbiota in both mothers and newborns. Taking into account the potential effects on maternal and consequently neonatal health, in this review, we analyzed the available data and discussed the current knowledge about the potential relationship between GDM and intestinal dysbiosis in mothers and newborns. In addition, we also discussed the influencing factors derived from GDM mothers on the gut microbiome of their newborns, including the vertical transmission of microbiota from mothers, the alteration of milk components of GDM mothers, and using of probiotics. Hoping that new insights into the role of the gut microbiota in GDM could lead to the development of integrated strategies to prevent and treat these metabolic disorders.
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Petrov ME, Jiao N, Panchanathan SS, Reifsnider E, Coonrod DV, Liu L, Krajmalnik-Brown R, Gu H, Davidson LA, Chapkin RS, Whisner CM. Protocol of the Snuggle Bug/Acurrucadito Study: a longitudinal study investigating the influences of sleep-wake patterns and gut microbiome development in infancy on rapid weight gain, an early risk factor for obesity. BMC Pediatr 2021; 21:374. [PMID: 34465311 PMCID: PMC8405858 DOI: 10.1186/s12887-021-02832-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 08/09/2021] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Overweight, obesity, and associated comorbidities are a pressing global issue among children of all ages, particularly among low-income populations. Rapid weight gain (RWG) in the first 6 months of infancy contributes to childhood obesity. Suboptimal sleep-wake patterns and gut microbiota (GM) have also been associated with childhood obesity, but little is known about their influences on early infant RWG. Sleep may alter the GM and infant metabolism, and ultimately impact obesity; however, data on the interaction between sleep-wake patterns and GM development on infant growth are scarce. In this study, we aim to investigate associations of infant sleep-wake patterns and GM development with RWG at 6 months and weight gain at 12 months. We also aim to evaluate whether temporal interactions exist between infant sleep-wake patterns and GM, and if these relations influence RWG. METHODS The Snuggle Bug/ Acurrucadito study is an observational, longitudinal study investigating whether 24-h, actigraphy-assessed, sleep-wake patterns and GM development are associated with RWG among infants in their first year. Based on the Ecological Model of Growth, we propose a novel conceptual framework to incorporate sleep-wake patterns and the GM as metabolic contributors for RWG in the context of maternal-infant interactions, and familial and socio-physical environments. In total, 192 mother-infant pairs will be recruited, and sleep-wake patterns and GM development assessed at 3 and 8 weeks, and 3, 6, 9, and 12 months postpartum. Covariates including maternal and child characteristics, family and environmental factors, feeding practices and dietary intake of infants and mothers, and stool-derived metabolome and exfoliome data will be assessed. The study will apply machine learning techniques combined with logistic time-varying effect models to capture infant growth and aid in elucidating the dynamic associations between study variables and RWG. DISCUSSION Repeated, valid, and objective assessment at clinically and developmentally meaningful intervals will provide robust measures of longitudinal sleep, GM, and growth. Project findings will provide evidence for future interventions to prevent RWG in infancy and subsequent obesity. The work also may spur the development of evidence-based guidelines to address modifiable factors that influence sleep-wake and GM development and prevent childhood obesity.
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Affiliation(s)
- Megan E Petrov
- Edson College of Nursing and Health Innovation, Arizona State University, 550 N. 3rd Street, Suite 301, Phoenix, AZ, 85004, USA
| | - Nana Jiao
- Edson College of Nursing and Health Innovation, Arizona State University, 550 N. 3rd Street, Suite 301, Phoenix, AZ, 85004, USA
| | - Sarada S Panchanathan
- Valleywise Comprehensive Health Center - Phoenix (Pediatric Clinic), 2525 E. Roosevelt St., Phoenix, AZ, 85008, USA
- College of Medicine Phoenix, University of Arizona, Phoenix, AZ, 85007, USA
| | - Elizabeth Reifsnider
- Edson College of Nursing and Health Innovation, Arizona State University, 550 N. 3rd Street, Suite 301, Phoenix, AZ, 85004, USA
| | - Dean V Coonrod
- Valleywise Health, Department of Obstetrics and Gynecology, 2525 E. Roosevelt St., Phoenix, AZ, 85008, USA
| | - Li Liu
- Biodesign Institute, Arizona State University, 1001 S. McAllister Ave BDA230B, Tempe, AZ, 85287, USA
| | - Rosa Krajmalnik-Brown
- Biodesign Swette Center for Environmental Biotechnology, Arizona State University, 1001 S. McAllister Ave, PO Box 875701, Tempe, AZ, 85287, USA
| | - Haiwei Gu
- College of Health Solutions, Arizona State University, 550 N. 3rd. Street, Suite 501, Phoenix, AZ, 85004, USA
| | - Laurie A Davidson
- Department of Nutrition and Food Science, Program in Integrative Nutrition and Complex Diseases, Texas A&M University, 2253 TAMU, 112 Cater-Mattil, College Station, TX, 77843, USA
| | - Robert S Chapkin
- Department of Nutrition and Food Science, Program in Integrative Nutrition and Complex Diseases, Texas A&M University, 2253 TAMU, 112 Cater-Mattil, College Station, TX, 77843, USA
| | - Corrie M Whisner
- College of Health Solutions, Arizona State University, 550 N. 3rd. Street, Suite 501, Phoenix, AZ, 85004, USA.
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16
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McGuire MK, McGuire MA. Microbiomes and Childhood Malnutrition: What Is the Evidence? ANNALS OF NUTRITION & METABOLISM 2021; 77:1-13. [PMID: 34515050 DOI: 10.1159/000519001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 08/11/2021] [Indexed: 11/19/2022]
Abstract
Both undernutrition and overnutrition continue to represent enduring global health crises, and with the growing implications of both forms of malnutrition occurring simultaneously in individuals and populations (referred to as the double burden of malnutrition), understanding their biological and environmental causes is a primary research and humanitarian necessity. There is growing evidence of a bidirectional association between variation in the gastrointestinal (GI) microbiome and risk of/resilience to malnutrition during early life. For example, studies of siblings who discordantly do or do not develop severe malnutrition show clear differences in the diversity and composition of fecal microbiomes. These differences are transiently lessened during refeeding but re-emerge thereafter. These findings have been somewhat recapitulated using animal models, but small sample sizes and limited range complicate interpretation of results and applicability to humans. Mechanisms driving these differences are currently unknown but likely involve a combination of inflammatory pathways (and perhaps antioxidant status of the host) and effects on nutrient availability, requirements, and utilization by both host and microbe. A less robust literature also suggests that variation in GI microbiome is associated with risk for obesity during childhood. The putative impact of GI microbiomes on malnutrition is likely modified by a variety of important variables such as genetics (likely driven, in part, by evolution), environmental pathogen exposure and its timing, dietary factors, and cultural/societal pattern (e.g., use of antibiotics). Given the growing double burden of malnutrition, this topic demands a focused interdisciplinary approach that expands from merely characterizing differences and longitudinal changes in fecal microbes to examining their functionality during early life. Understanding the complex composition of human milk and how its components impact establishment and maintenance of the recipient infant's GI microbiome will also undoubtedly shed important light on this topic.
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Affiliation(s)
- Michelle K McGuire
- Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, Idaho, USA
| | - Mark A McGuire
- Department of Animal, Veterinary, and Food Sciences, University of Idaho, Moscow, Idaho, USA
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17
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Suwaydi MA, Gridneva Z, Perrella SL, Wlodek ME, Lai CT, Geddes DT. Human Milk Metabolic Hormones: Analytical Methods and Current Understanding. Int J Mol Sci 2021; 22:ijms22168708. [PMID: 34445437 PMCID: PMC8395916 DOI: 10.3390/ijms22168708] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/30/2021] [Accepted: 08/09/2021] [Indexed: 02/07/2023] Open
Abstract
Human milk (HM) contains a wide array of peptide hormones including leptin and adiponectin, which are involved in the regulation of infant growth and development. These essential hormones might play an important role in the regulation of metabolic reprogramming of the new-born infant. However, HM hormone studies are sparse and heterogeneous in regard to the study design, sample collection, preparation and analysis methods. This review discussed the limitations of HM hormone analysis highlighting the gaps in pre-analytical and analytical stages. The methods used to quantify HM metabolic hormones (leptin, adiponectin, ghrelin, insulin, obestatin, resistin and apelin) can be classified as immunoassay, immunosensor and chromatography. Immunoassay methods (ELISA and RIA) have been predominantly used in the measurement of these HM hormones. The relative validity parameters of HM hormones analysis are often overlooked in publications, despite the complexity and differences of HM matrix when compared to that of plasma and urine. Therefore, appropriate reports of validation parameters of methodology and instrumentation are crucial for accurate measurements and therefore better understanding of the HM metabolic hormones and their influences on infant outcomes.
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Affiliation(s)
- Majed A. Suwaydi
- School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia; (M.A.S.); (S.L.P.); (M.E.W.); (C.T.L.); (D.T.G.)
- Department of Medical Laboratory Technology, College of Applied Medical Sciences, Jazan University, Jazan 54142, Saudi Arabia
| | - Zoya Gridneva
- School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia; (M.A.S.); (S.L.P.); (M.E.W.); (C.T.L.); (D.T.G.)
- Correspondence: ; Tel.: +61-8-6488-4467
| | - Sharon L. Perrella
- School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia; (M.A.S.); (S.L.P.); (M.E.W.); (C.T.L.); (D.T.G.)
| | - Mary E. Wlodek
- School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia; (M.A.S.); (S.L.P.); (M.E.W.); (C.T.L.); (D.T.G.)
- Population Health, Murdoch Children’s Research Institute (MCRI), Parkville, VIC 3052, Australia
| | - Ching Tat Lai
- School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia; (M.A.S.); (S.L.P.); (M.E.W.); (C.T.L.); (D.T.G.)
| | - Donna T. Geddes
- School of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, Australia; (M.A.S.); (S.L.P.); (M.E.W.); (C.T.L.); (D.T.G.)
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18
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Ioannou A, Knol J, Belzer C. Microbial Glycoside Hydrolases in the First Year of Life: An Analysis Review on Their Presence and Importance in Infant Gut. Front Microbiol 2021; 12:631282. [PMID: 34122357 PMCID: PMC8194493 DOI: 10.3389/fmicb.2021.631282] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 05/03/2021] [Indexed: 01/15/2023] Open
Abstract
The first year of life is a crucial period during which the composition and functionality of the gut microbiota develop to stabilize and resemble that of adults. Throughout this process, the gut microbiota has been found to contribute to the maturation of the immune system, in gastrointestinal physiology, in cognitive advancement and in metabolic regulation. Breastfeeding, the “golden standard of infant nutrition,” is a cornerstone during this period, not only for its direct effect but also due to its indirect effect through the modulation of gut microbiota. Human milk is known to contain indigestible carbohydrates, termed human milk oligosaccharides (HMOs), that are utilized by intestinal microorganisms. Bacteria that degrade HMOs like Bifidobacterium longum subsp. infantis, Bifidobacterium bifidum, and Bifidobacterium breve dominate the infant gut microbiota during breastfeeding. A number of carbohydrate active enzymes have been found and identified in the infant gut, thus supporting the hypothesis that these bacteria are able to degrade HMOs. It is suggested that via resource-sharing and cross-feeding, the initial utilization of HMOs drives the interplay within the intestinal microbial communities. This is of pronounced importance since these communities promote healthy development and some of their species also persist in the adult microbiome. The emerging production and accessibility to metagenomic data make it increasingly possible to unravel the metabolic capacity of entire ecosystems. Such insights can increase understanding of how the gut microbiota in infants is assembled and makes it a possible target to support healthy growth. In this manuscript, we discuss the co-occurrence and function of carbohydrate active enzymes relevant to HMO utilization in the first year of life, based on publicly available metagenomic data. We compare the enzyme profiles of breastfed children throughout the first year of life to those of formula-fed infants.
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Affiliation(s)
- Athanasia Ioannou
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, Netherlands
| | - Jan Knol
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, Netherlands.,Danone Nutricia Research, Utrecht, Netherlands
| | - Clara Belzer
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, Netherlands
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Verduci E, Calcaterra V, Di Profio E, Fiore G, Rey F, Magenes VC, Todisco CF, Carelli S, Zuccotti GV. Brown Adipose Tissue: New Challenges for Prevention of Childhood Obesity. A Narrative Review. Nutrients 2021; 13:1450. [PMID: 33923364 PMCID: PMC8145569 DOI: 10.3390/nu13051450] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/14/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
Pediatric obesity remains a challenge in modern society. Recently, research has focused on the role of the brown adipose tissue (BAT) as a potential target of intervention. In this review, we revised preclinical and clinical works on factors that may promote BAT or browning of white adipose tissue (WAT) from fetal age to adolescence. Maternal lifestyle, type of breastfeeding and healthy microbiota can affect the thermogenic activity of BAT. Environmental factors such as exposure to cold or physical activity also play a role in promoting and activating BAT. Most of the evidence is preclinical, although in clinic there is some evidence on the role of omega-3 PUFAs (EPA and DHA) supplementation on BAT activation. Clinical studies are needed to dissect the early factors and their modulation to allow proper BAT development and functions and to prevent onset of childhood obesity.
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Affiliation(s)
- Elvira Verduci
- Department of Health Sciences, University of Milan, 20146 Milan, Italy
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, 20154 Milan, Italy; (V.C.); (E.D.P.); (G.F.); (V.C.M.); (C.F.T.); (G.V.Z.)
| | - Valeria Calcaterra
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, 20154 Milan, Italy; (V.C.); (E.D.P.); (G.F.); (V.C.M.); (C.F.T.); (G.V.Z.)
- Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy
| | - Elisabetta Di Profio
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, 20154 Milan, Italy; (V.C.); (E.D.P.); (G.F.); (V.C.M.); (C.F.T.); (G.V.Z.)
- Department of Animal Sciences for Health, Animal Production and Food Safety, University of Milan, 20133 Milan, Italy
| | - Giulia Fiore
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, 20154 Milan, Italy; (V.C.); (E.D.P.); (G.F.); (V.C.M.); (C.F.T.); (G.V.Z.)
| | - Federica Rey
- Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, 20157 Milan, Italy;
- Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, University of Milan, 20157 Milan, Italy
| | - Vittoria Carlotta Magenes
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, 20154 Milan, Italy; (V.C.); (E.D.P.); (G.F.); (V.C.M.); (C.F.T.); (G.V.Z.)
| | - Carolina Federica Todisco
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, 20154 Milan, Italy; (V.C.); (E.D.P.); (G.F.); (V.C.M.); (C.F.T.); (G.V.Z.)
| | - Stephana Carelli
- Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, 20157 Milan, Italy;
- Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, University of Milan, 20157 Milan, Italy
| | - Gian Vincenzo Zuccotti
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, University of Milan, 20154 Milan, Italy; (V.C.); (E.D.P.); (G.F.); (V.C.M.); (C.F.T.); (G.V.Z.)
- Department of Biomedical and Clinical Sciences “L. Sacco”, University of Milan, 20157 Milan, Italy;
- Pediatric Clinical Research Center Fondazione Romeo ed Enrica Invernizzi, University of Milan, 20157 Milan, Italy
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20
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Prins-van Ginkel AC, Wijga AH, Bruijning-Verhagen PCJ, Brunekreef B, Gehring U, van der Hoek W, Koppelman GH, van Rossem L, van der Sande MAB, Smit HA. Early childhood infections and body mass index in adolescence. Int J Obes (Lond) 2021; 45:1143-1151. [PMID: 33772146 DOI: 10.1038/s41366-021-00806-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 02/04/2021] [Accepted: 02/23/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND The incidence of childhood overweight and obesity is rising. It is hypothesized that infections in early childhood are associated with being overweight. This study investigated the association between the number of symptomatic infections or antibiotic prescriptions in the first 3 years of life and body mass index (BMI) in adolescence. SUBJECTS The current study is part of the Prevention and Incidence of Asthma and Mite Allergy population-based birth cohort study. Weight and height were measured by trained research staff at ages 12 and 16 years. The 3015 active participants at age 18 years were asked for informed consent for general practitioner (GP) data collection and 1519 gave written informed consent. Studied exposures include (1) GP-diagnosed infections, (2) antibiotic prescriptions, and (3) parent-reported infections in the first 3 years of life. Generalized estimating equation analysis was used to determine the association between each of these exposures and BMI z-score. RESULTS Exposure data and BMI measurement in adolescence were available for 622 participants. The frequencies of GP-diagnosed infections and antibiotic prescriptions were not associated with BMI z-score in adolescence with estimates being 0.14 (95% CI -0.09-0.37) and 0.10 (95% CI -0.14-0.34) for the highest exposure categories, respectively. Having ≥6 parent-reported infections up to age 3 years was associated with a 0.23 (95% CI 0.01-0.44) higher BMI z-score compared to <2 parent-reported infections. CONCLUSIONS For all infectious disease measures an increase in BMI z-score for the highest childhood exposure to infectious disease was observed, although only statistically significant for parent-reported infections. These results do not show an evident link with infection severity, but suggest a possible cumulative effect of repeated symptomatic infections on overweight development.
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Affiliation(s)
- Annemarijn C Prins-van Ginkel
- Center for Infectious Diseases, Epidemiology, and Surveillance, National Institute for Public Health and the Environment, Bilthoven, The Netherlands. .,Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
| | - Alet H Wijga
- Center for Nutrition, Prevention, and Health Services, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - Patricia C J Bruijning-Verhagen
- Center for Infectious Diseases, Epidemiology, and Surveillance, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.,Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Bert Brunekreef
- Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
| | - Ulrike Gehring
- Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
| | - Wim van der Hoek
- Center for Infectious Diseases, Epidemiology, and Surveillance, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
| | - Gerard H Koppelman
- Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.,GRIAC Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Lenie van Rossem
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Marianne A B van der Sande
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.,Department of Public Health, Institute of Tropical Medicine, Antwerp, Belgium
| | - Henriëtte A Smit
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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21
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Obesity, Early Life Gut Microbiota, and Antibiotics. Microorganisms 2021; 9:microorganisms9020413. [PMID: 33671180 PMCID: PMC7922584 DOI: 10.3390/microorganisms9020413] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 02/09/2021] [Accepted: 02/15/2021] [Indexed: 02/07/2023] Open
Abstract
Obesity is a major public health problem that continues to be one of the leading risk factors for premature death. Early life is a critical period of time when the gut microbiota and host metabolism are developing in tandem and significantly contribute to long-term health outcomes. Dysbiosis of the gut microbiota, particularly in early life, can have detrimental effects on host health and increase the susceptibility of developing obesity later in life. Antibiotics are an essential lifesaving treatment; however, their use in early life may not be without risk. Antibiotics are a leading cause of intestinal dysbiosis, and early life administration is associated with obesity risk. The following review explores the relevant literature that simultaneously examines antibiotic-induced dysbiosis and obesity risk. Current evidence suggests that disruptions to the composition and maturation of the gut microbiota caused by antibiotic use in early life are a key mechanism linking the association between antibiotics and obesity. Without compromising clinical practice, increased consideration of the long-term adverse effects of antibiotic treatment on host health, particularly when used in early life is warranted. Novel adjunct interventions should be investigated (e.g., prebiotics) to help mitigate metabolic risk when antibiotic treatment is clinically necessary.
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22
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Mansour EN, Elwakeel ME, Elaziz OHA, Shipl WM. Lipopolysaccharide Binding Protein and Cardiovascular Changes in Obese Children. OPEN JOURNAL OF PEDIATRICS 2021; 11:225-237. [DOI: 10.4236/ojped.2021.112022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
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Słabuszewska-Jóźwiak A, Szymański JK, Ciebiera M, Sarecka-Hujar B, Jakiel G. Pediatrics Consequences of Caesarean Section-A Systematic Review and Meta-Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E8031. [PMID: 33142727 PMCID: PMC7662709 DOI: 10.3390/ijerph17218031] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/13/2020] [Revised: 10/28/2020] [Accepted: 10/29/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Cesarean section is a surgical procedure, which is the most frequently performed in gynecology and obstetrics. It is commonly believed that an operative delivery is a less painful and safer mode of delivery, which translates into an increasing number of the procedures performed without medical indications. The maternal sequelae of cesarean sections are well elucidated and widely discussed in the literature, while long-term neonatal consequences still remain the issue of research and scientific dispute. The aim of the present paper was to perform a systematic review of current literature regarding pediatrics consequences of cesarean section. METHODS We reviewed available data from PubMed, Science Direct as well as Google Scholar bases concerning early and long-term neonatal sequelae of operative deliveries. The following key words were used: "cesarean section", "caesarean section", "neonatal outcomes", "respiratory disorders", "asthma", "obesity", "overweight", and "neurological disorders". A total of 1636 papers were retrieved out of which 27 were selected for the final systematic review whereas 16 articles provided data for meta-analysis. Statistical analyses were performed using RevMan 5.4. To determine the strength of association between the caesarean section and respiratory tract infections, asthma, diabetes type 1 as well as obesity the pooled odds ratios (OR) with the 95% confidence intervals (CI) were calculated. RESULTS Conducted meta-analyses revealed that caesarean section is a risk factor for respiratory tract infections (pooled OR = 1.30 95%CI 1.06-1.60, p = 0.001), asthma (pooled OR = 1.23 95%CI 1.14-1.33, p < 0.00001) as well as obesity (pooled OR = 1.35 95%CI 1.29-1.41, p < 0.00001) in offspring. CONCLUSIONS The results of the studies included indicated that children delivered by cesarean section more commonly developed respiratory tract infections, obesity and the manifestations of asthma than children delivered vaginally. The risk of developing diabetes mellitus type 1 or neurological disorders in offspring after caesarean section is still under discussion.
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Affiliation(s)
- Aneta Słabuszewska-Jóźwiak
- First Department of Obstetrics and Gynaecology, Centre of Postgraduate Medical Education, Żelazna 90 Street, 01-004 Warsaw, Poland; (J.K.S.); (G.J.)
| | - Jacek Krzysztof Szymański
- First Department of Obstetrics and Gynaecology, Centre of Postgraduate Medical Education, Żelazna 90 Street, 01-004 Warsaw, Poland; (J.K.S.); (G.J.)
| | - Michał Ciebiera
- Second Department of Obstetrics and Gynaecology, Centre of Postgraduate Medical Education, Cegłowska 80 Street, 01-809 Warsaw, Poland;
| | - Beata Sarecka-Hujar
- Department of Basic Biomedical Science, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, Kasztanowa 3 Street, 41-200 Sosnowiec, Poland;
| | - Grzegorz Jakiel
- First Department of Obstetrics and Gynaecology, Centre of Postgraduate Medical Education, Żelazna 90 Street, 01-004 Warsaw, Poland; (J.K.S.); (G.J.)
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24
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Gut Microbiota and Obesity: A Role for Probiotics. Nutrients 2019; 11:nu11112690. [PMID: 31703257 PMCID: PMC6893459 DOI: 10.3390/nu11112690] [Citation(s) in RCA: 382] [Impact Index Per Article: 63.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2019] [Revised: 09/23/2019] [Accepted: 09/24/2019] [Indexed: 02/07/2023] Open
Abstract
Nowadays, obesity is one of the most prevalent human health problems. Research from the last 30 years has clarified the role of the imbalance between energy intake and expenditure, unhealthy lifestyle, and genetic variability in the development of obesity. More recently, the composition and metabolic functions of gut microbiota have been proposed as being able to affect obesity development. Here, we will report the current knowledge on the definition, composition, and functions of intestinal microbiota. We have performed an extensive review of the literature, searching for the following keywords: metabolism, gut microbiota, dysbiosis, obesity. There is evidence for the association between gut bacteria and obesity both in infancy and in adults. There are several genetic, metabolic, and inflammatory pathophysiological mechanisms involved in the interplay between gut microbes and obesity. Microbial changes in the human gut can be considered a factor involved in obesity development in humans. The modulation of the bacterial strains in the digestive tract can help to reshape the metabolic profile in the human obese host as suggested by several data from animal and human studies. Thus, a deep revision of the evidence pertaining to the use probiotics, prebiotics, and antibiotics in obese patients is conceivable
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25
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Dietary intake influences gut microbiota development of healthy Australian children from the age of one to two years. Sci Rep 2019; 9:12476. [PMID: 31462648 PMCID: PMC6713781 DOI: 10.1038/s41598-019-48658-4] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Accepted: 08/08/2019] [Indexed: 02/07/2023] Open
Abstract
Early life nutrition is a vital determinant of an individual’s life-long health and also directly influences the ecological and functional development of the gut microbiota. However, there are limited longitudinal studies examining the effect of diet on the gut microbiota development in early childhood. Here, up to seven stool samples were collected from each of 48 healthy children during their second year of life, and microbiota dynamics were assessed using 16S rRNA gene amplicon sequencing. Children’s dietary information was also collected during the same period using a validated food frequency questionnaire designed for this age group, over five time points. We observed significant changes in gut microbiota community, concordant with changes in the children’s dietary pattern over the 12-month period. In particular, we found differential effects on specific Firmicutes-affiliated lineages in response to frequent intake of either processed or unprocessed foods. Additionally, the consumption of fortified milk supplemented with a Bifidobacterium probiotic and prebiotics (synbiotics) further increased the presence of Bifidobacterium spp., highlighting the potential use of synbiotics to prolong and sustain changes in these lineages and shaping the gut microbiota community in young children.
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26
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McLean C, Jun S, Kozyrskyj A. Impact of maternal smoking on the infant gut microbiota and its association with child overweight: a scoping review. World J Pediatr 2019; 15:341-349. [PMID: 31290060 DOI: 10.1007/s12519-019-00278-8] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Accepted: 06/13/2019] [Indexed: 01/28/2023]
Abstract
BACKGROUND Childhood obesity is a growing public health concern with evidence demonstrating that while infant exposure to maternal smoking is linked to low birth weight at birth, there is a rapid catch up in weight and increased risk of obesity in later life. This scoping review aims to synthesize up-to-date evidence on the impact of maternal smoking on the infant gut microbiota and its association with child overweight. METHODS We conducted a PRISMA-compliant scoping review. Primary population-based cohort studies published between 1900 and April 2018 were included. Relevant publications were retrieved from seven databases: PubMed, Medline, Embase, Scopus, Biosis, Cochrane library, and Web of Science Core Collection. RESULTS A total of three prospective cohort studies were included which utilized high-throughput 16S rRNA gene sequencing to assess the gut microbiota and included a total of 1277 infant/neonatal participants. Neonates exposed to environmental smoke had a higher relative abundance of Ruminococcus and Akkermansia. Infants exposed to environmental smoke during pregnancy or postnatally were found to have increased gut bacterial richness, particularly Firmicutes at 3 months of age, while 6-month-old infants born to smoking mothers had an increased abundance of Bacteroides and Staphylococcus. Elevated Firmicutes richness at 3 months of age was associated with elevated odds of child overweight and obesity at 1 and 3 years of age. CONCLUSION The limited evidence to date warrants further large scale, longitudinal studies to explore the impact of maternal smoking and environmental tobacco smoke on the infant gut microbiome and its relation to child overweight.
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Affiliation(s)
- Cara McLean
- Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Canada
| | - Shelly Jun
- Department of Pediatrics, University of Alberta, 3-527 Edmonton Clinic Health Academy, 11405-87 Avenue, Edmonton, AB, T6G 1C9, Canada
| | - Anita Kozyrskyj
- Department of Pediatrics, University of Alberta, 3-527 Edmonton Clinic Health Academy, 11405-87 Avenue, Edmonton, AB, T6G 1C9, Canada.
- School of Public Health, University of Alberta, Edmonton, Canada.
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27
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Dawson-Hahn EE, Rhee KE. The association between antibiotics in the first year of life and child growth trajectory. BMC Pediatr 2019; 19:23. [PMID: 30651086 PMCID: PMC6335775 DOI: 10.1186/s12887-018-1363-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Accepted: 12/04/2018] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND Antibiotics are frequently prescribed to children, and may be an environmental influence that contributes to the increasing prevalence of childhood obesity. The aim of this study was to examine the effect of antibiotic use in the first year of life on child growth trajectories from birth to age 6 years including significant covariates. METHODS Data from 586 children in the Infant Feeding Practices II (IFPS II) and 6 year follow-up study (6YFU) were included. Antibiotic exposures, weight and height measurements were collected from birth through the first 12 months, and then again at 6 years. Linear mixed effects growth modeling, controlling for exclusive breastfeeding, socio-demographic factors, smoking during pregnancy, gestational diabetes, and maternal pre-pregnancy weight status, was used to examine the association between antibiotic exposure and child growth trajectories through age 6 years. RESULTS The majority of infants (60.58%) did not receive any antibiotics; 33.79% received 1-2 courses and 5.63% received 3 or more antibiotic courses during the first year. In the unadjusted model, children with 1-2 antibiotic exposures had a 0.17 (SE 0.08) higher rate of change in BMI z-score (BMIz) than children without any antibiotics, and children with ≥3 exposures had a 0.42 (SE 0.16) higher rate of change in BMIz (p = 0.009). Growth trajectory over time for those who had ≥3 antibiotics was greater than those without any antibiotics (p = 0.002). CONCLUSIONS Efforts to guide the judicious use of antibiotics should continue, particularly in the first year of life.
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Affiliation(s)
- Elizabeth E. Dawson-Hahn
- Department of Pediatrics, University of Washington, Seattle, WA USA
- Seattle Children’s Research Institute, Center for Child Health, Behavior and Development, M/S CW8-6, PO Box 5371, Seattle, WA 98145 USA
| | - Kyung E. Rhee
- Department of Pediatrics, UCSD School of Medicine, University of California San Diego, 9500 Gilman Drive, MC 0874, La Jolla, CA, San Diego, CA 92093 USA
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Werlang ICR, Mueller NT, Pizoni A, Wisintainer H, Matte U, Costa SHDAM, Ramos JGL, Goldani MZ, Dominguez-Bello MG, Goldani HAS. Associations of birth mode with cord blood cytokines, white blood cells, and newborn intestinal bifidobacteria. PLoS One 2018; 13:e0205962. [PMID: 30388115 PMCID: PMC6214518 DOI: 10.1371/journal.pone.0205962] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 10/04/2018] [Indexed: 01/15/2023] Open
Abstract
The associations of Cesarean delivery with offspring metabolic and immune-mediated diseases are believed to derive from lack of mother-to-newborn transmission of specific microbes at birth. Bifidobacterium spp., in particular, has been hypothesized to play a health-promoting role, yet little is known about how delivery mode modifies colonization of the newborn by this group of microbes. The aim of this research was to examine the presence of Bifidobacterium in meconium and in the transitional stool, and to assess cytokine levels and hematological parameters in the venous cord blood of infants born by elective, pre-labor Cesarean section vs. vaginal delivery in Southern Brazil. We recruited 89 mother-newborn pairs (23 vaginal delivery and 66 elective cesarean delivery), obtained demographic information from a structured questionnaire and clinical information from medical records. We obtained umbilical cord venous blood and meconium samples following delivery and the transitional stool (the first defecation after meconium) before discharge. We determined plasma levels of IL-1β, IL-10, IL-6, GM-CSF, IL-5, IFN-γ, TNF-α, IL-2, IL-4 and IL-8 in the cord blood, and presence of stool Bifidobacterium by real time PCR. Compared to vaginally-delivered neonates, Cesarean-delivered neonates had a lower leukocyte count (p = 0.037), lower hemoglobin (p = 0.04), and lower levels of the cytokine GM-CSF (p = 0.009) in the cord blood. Moreover, Bifidobacterium was detected less often in the transitional stool of Cesarean-delivered neonates compared to vaginally-delivered neonates (p = 0.001). The results indicate that pre-labor Cesarean birth may be associated with microbial and hematological alterations in the neonate. The clinical significance of these findings remains to be determined in larger prospective birth cohort studies.
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Affiliation(s)
- Isabel Cristina Ribas Werlang
- Laboratory of Translational Pediatrics, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul. Porto Alegre–RS, Brazil
- Post-Graduate Program in Health of Child and Adolescent, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul. Porto Alegre–RS, Brazil
| | - Noel Theodore Mueller
- Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America
- Welch Center for Epidemiology, Prevention, and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America
| | - Aline Pizoni
- Laboratory of Translational Pediatrics, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul. Porto Alegre–RS, Brazil
- Post-Graduate Program Sciences in Gastroenterology and Hepatology, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul. Porto Alegre–RS, Brazil
| | | | - Ursula Matte
- Department of Genetics, Universidade Federal do Rio Grande do Sul. Porto Alegre–RS, Brazil
| | - Sergio Hofmeister de Almeida Martins Costa
- Department of Gynecology and Obstetrics, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul and Hospital Mae de Deus. Porto Alegre–RS, Brazil
| | - Jose Geraldo Lopes Ramos
- Department of Gynecology and Obstetrics, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul and Hospital Mae de Deus. Porto Alegre–RS, Brazil
| | - Marcelo Zubaran Goldani
- Laboratory of Translational Pediatrics, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul. Porto Alegre–RS, Brazil
- Post-Graduate Program in Health of Child and Adolescent, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul. Porto Alegre–RS, Brazil
| | - Maria Gloria Dominguez-Bello
- Department of Biochemistry and Microbiology and of Anthropology, Rutgers University, New Brunswick, New Jersey, United States of America
| | - Helena Ayako Sueno Goldani
- Laboratory of Translational Pediatrics, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul. Porto Alegre–RS, Brazil
- Post-Graduate Program in Health of Child and Adolescent, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul. Porto Alegre–RS, Brazil
- Post-Graduate Program Sciences in Gastroenterology and Hepatology, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul. Porto Alegre–RS, Brazil
- * E-mail:
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29
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Gut Microbiota in the First 2 Years of Life and the Association with Body Mass Index at Age 12 in a Norwegian Birth Cohort. mBio 2018; 9:mBio.01751-18. [PMID: 30352933 PMCID: PMC6199494 DOI: 10.1128/mbio.01751-18] [Citation(s) in RCA: 110] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Childhood obesity is a growing problem worldwide. Recent research suggests that the gut microbiota may play an important and potentially causal role in the development of obesity and may be one mechanism that explains the transgenerational transmission of obesity risk. Here we examine the early-life gut microbiota at days 4, 10, 30, 120, 365, and 730 and the association with body mass index (BMI) z-scores at age 12 in a Norwegian prospective cohort (n = 165), and evaluate how these BMI-associated taxa relate to maternal overweight/obesity (Ow/Ob) and excessive gestational weight gain (GWG). We performed 16S rRNA gene sequencing on the gut microbiota samples. Taxonomic phylogeny at days 10 and 730 was significantly associated with childhood BMI, and the gut microbiota taxa at two years of age explained over 50% of the variation in childhood BMI in this cohort. The subset of the early-life taxa within the gut microbiota that best predicted later childhood BMI showed substantial overlap with the maternal taxa most strongly associated with maternal Ow/Ob and excessive GWG. Our results show an association between the infant gut microbiota and later BMI, and they offer preliminary evidence that the infant gut microbiota, particularly at 2 years of age, may have potential to help identify children at risk for obesity.IMPORTANCE Understanding the role of the early-life gut microbiota in obesity is important because there may be opportunities for preventive strategies. We examined the relationships between infant gut microbiota at six times during the first two years of life and BMI at age 12 in a birth cohort of 165 children and their mothers. We found that the gut microbiota from early life to two years shows an increasingly strong association with childhood BMI. This study provides preliminary evidence that the gut microbiome at 2 years of age may offer useful information to help to identify youth who are at risk for obesity, which could facilitate more-targeted early prevention efforts.
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Gridneva Z, Kugananthan S, Rea A, Lai CT, Ward LC, Murray K, Hartmann PE, Geddes DT. Human Milk Adiponectin and Leptin and Infant Body Composition over the First 12 Months of Lactation. Nutrients 2018; 10:nu10081125. [PMID: 30127292 PMCID: PMC6115716 DOI: 10.3390/nu10081125] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 08/17/2018] [Accepted: 08/17/2018] [Indexed: 12/26/2022] Open
Abstract
Human milk (HM) adipokines may influence infant feeding patterns, appetite regulation, and body composition (BC). The associations between concentrations/calculated daily intakes (CDI) of HM adipokines in the first 12 months postpartum and maternal/term infant BC, and infant breastfeeding parameters were investigated. BC of breastfeeding dyads (n = 20) was measured at 2, 5, 9, and/or 12 months postpartum with ultrasound skinfolds (infants) and bioimpedance spectroscopy (infants/mothers). 24-h milk intake and feeding frequency were measured along with whole milk adiponectin and skim and whole milk leptin (SML and WML) and CDI were calculated. Statistical analysis used linear regression/mixed effects models; results were adjusted for multiple comparisons. Adipokine concentrations did not associate with infant BC. Higher CDI of adiponectin were associated with lower infant fat-free mass (FFM; p = 0.005) and FFM index (FFMI; p = 0.009) and higher fat mass (FM; p < 0.001), FM index (FMI; p < 0.001), and %FM (p < 0.001). Higher CDI of SML were associated with higher infant FM (p < 0.001), FMI (p < 0.001), and %FM (p = 0.002). At 12 months, higher CDI of WML were associated with larger increases in infant adiposity (2–12 month: FM, p = 0.0006; %FM, p = 0.0004); higher CDI of SML were associated with a larger decrease in FFMI (5–12 months: p = 0.0004). Intakes of HM adipokines differentially influence development of infant BC in the first year of life, which is a critical window of infant programming and may potentially influence risk of later disease via modulation of BC.
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Affiliation(s)
- Zoya Gridneva
- School of Molecular Sciences, M310, The University of Western Australia, Crawley, Perth, WA 6009, Australia.
| | - Sambavi Kugananthan
- School of Molecular Sciences, M310, The University of Western Australia, Crawley, Perth, WA 6009, Australia.
- School of Human Sciences, The University of Western Australia, Crawley, Perth, WA 6009, Australia.
| | - Alethea Rea
- Centre for Applied Statistics, The University of Western Australia, Crawley, Perth, WA 6009, Australia.
| | - Ching Tat Lai
- School of Molecular Sciences, M310, The University of Western Australia, Crawley, Perth, WA 6009, Australia.
| | - Leigh C Ward
- School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Brisbane, QLD 4072, Australia.
| | - Kevin Murray
- School of Population and Global Health, The University of Western Australia, Crawley, Perth, WA 6009, Australia.
| | - Peter E Hartmann
- School of Molecular Sciences, M310, The University of Western Australia, Crawley, Perth, WA 6009, Australia.
| | - Donna T Geddes
- School of Molecular Sciences, M310, The University of Western Australia, Crawley, Perth, WA 6009, Australia.
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Mohamad M, Loy SL, Lim PY, Wang Y, Soo KL, Mohamed HJJ. Maternal Serum and Breast Milk Adiponectin: The Association with Infant Adiposity Development. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2018; 15:E1250. [PMID: 29895806 PMCID: PMC6025015 DOI: 10.3390/ijerph15061250] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/29/2018] [Revised: 06/08/2018] [Accepted: 06/11/2018] [Indexed: 12/21/2022]
Abstract
The prevalence of childhood obesity is increasing at an alarming rate in Malaysia. Metabolic changes during pregnancy are critical to the development of infant adiposity, due to imbalanced adipokines production. Hence, we aimed to investigate the association of maternal serum and breast milk adipokines with infant adiposity development. The study was conducted from April 2010 until December 2012. A total of 155 healthy pregnant mothers aged 19 to 40 years were recruited during the first and second trimester in Kelantan, Malaysia. Data consisted of maternal sociodemographic details, anthropometry and clinical biochemistry analysis; and the infant’s anthropometry and feeding patterns. Maternal fasting serum and breast milk samples were analysed for adiponectin and leptin levels. Data collection was performed in the second and third trimester of pregnancy, and continued with follow-up visits at birth, two, six, and 12 months postpartum. Multiple linear regression (MLR) analyses were performed to examine the associations between maternal serum and breast milk adiponectin and leptin and infant adiposity development. MLR models showed that, in the first year, as maternal serum and breast milk adiponectin increased, infant weight, BMI-for-age Z scores and abdominal circumference significantly decreased (p < 0.05). Maternal serum and/or breast milk adiponectin was associated with first-year infant adiposity development.
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Affiliation(s)
- Marhazlina Mohamad
- School of Nutrition and Dietetics, Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Kuala Nerus, Terengganu 21300, Malaysia.
| | - See Ling Loy
- Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore 229899, Singapore.
| | - Poh Ying Lim
- Department of Community Health, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM, Serdang 43400, Malaysia.
| | - Yu Wang
- Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
| | - Kah Leng Soo
- Nutrition and Dietetics Programme, School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia.
| | - Hamid Jan Jan Mohamed
- Nutrition and Dietetics Programme, School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan 16150, Malaysia.
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Abstract
Early nutrition may have long-lasting metabolic impacts in adulthood. Even though breast milk is the gold standard, most infants are at least partly formula-fed. Despite obvious improvements, infant formulas remain perfectible to reduce the gap between breastfed and formula-fed infants. Improvements such as reducing the protein content, modulating the lipid matrix and adding prebiotics, probiotics and synbiotics, are discussed regarding metabolic health. Numerous questions remain to be answered on how impacting the infant formula composition may modulate the host metabolism and exert long-term benefits. Interactions between early nutrition (composition of human milk and infant formula) and the gut microbiota profile, as well as mechanisms connecting gut microbiota to metabolic health, are highlighted. Gut microbiota stands as a key actor in the nutritional programming but additional well-designed longitudinal human studies are needed.
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Montoya-Williams D, Lemas DJ, Spiryda L, Patel K, Carney OO, Neu J, Carson TL. The Neonatal Microbiome and Its Partial Role in Mediating the Association between Birth by Cesarean Section and Adverse Pediatric Outcomes. Neonatology 2018; 114:103-111. [PMID: 29788027 PMCID: PMC6532636 DOI: 10.1159/000487102] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Accepted: 01/23/2018] [Indexed: 12/26/2022]
Abstract
BACKGROUND Cesarean sections (CS) are among the most commonly performed surgical procedures in the world. Epidemiologic data has associated delivery by CS with an increased risk of certain adverse health outcomes in children, such as asthma and obesity. OBJECTIVE To explore what is known about the effect of mode of delivery on the development of the infant microbiome and discuss the potentially mediating role of CS-related microbial dysbiosis in the development of adverse pediatric health outcomes. Recommendations for future inquiry are also provided. METHODS This study provides a narrative overview of the literature synthesizing the findings of literature retrieved from searches of PubMed and other computerized databases and authoritative texts. RESULTS Emerging evidence suggests that mode of delivery is involved in the development of the neonatal microbiome and may partially explain pediatric health outcomes associated with birth by CS. Specifically, the gut microbiome of vaginally delivered infants more closely resembles their mothers' vaginal microbiome and thus more commonly consists of potentially beneficial microbiota such as Lactobacillus, Bifidobacterium, and Bacteroides. Conversely, the microbiome of infants born via CS shows an increased prevalence of either skin flora or potentially pathogenic microbial communities such as Klebsiella, Enterococcus, and Clostridium. CONCLUSIONS Mode of delivery plays an important role in the development of the postnatal microbiome but likely tells only part of the story. More comprehensive investigations into all the pre- and perinatal factors that have the potential to contribute to the neonatal microbiome are warranted.
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Affiliation(s)
- Diana Montoya-Williams
- Division of Neonatology, Department of Pediatrics, University of Florida, Gainesville, Florida, USA
| | - Dominick J Lemas
- Department of Health Outcomes and Biomedical Informatics, University of Florida, Gainesville, Florida, USA
| | - Lisa Spiryda
- Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida, USA
| | - Keval Patel
- Department of Health Outcomes and Biomedical Informatics, University of Florida, Gainesville, Florida, USA
| | - O'neshia Olivia Carney
- Department of Health Outcomes and Biomedical Informatics, University of Florida, Gainesville, Florida, USA
| | - Josef Neu
- Division of Neonatology, Department of Pediatrics, University of Florida, Gainesville, Florida, USA
| | - Tiffany L Carson
- Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
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Colonic Bacteroides are positively associated with trabecular bone structure and programmed by maternal vitamin D in male but not female offspring in an obesogenic environment. Int J Obes (Lond) 2017; 42:696-703. [PMID: 29188819 DOI: 10.1038/ijo.2017.294] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2017] [Revised: 10/03/2017] [Accepted: 11/06/2017] [Indexed: 01/09/2023]
Abstract
BACKGROUND/OBJECTIVES The gut microbiota is determined early in life, possibly including pregnancy. Pioneering data suggest vitamin D, a nutrient important for bone health, affects this microbiota. We found that high maternal vitamin D lowered circulating lipopolysaccharide (LPS), improved intestinal barrier and bone health in male but not female offspring in an obesogenic environment. This study determined if high maternal dietary vitamin D programs Bacteroides and Prevotella and whether this associates with bone mineral content, density and structure of male and female adult offspring fed an obesogenic diet. METHODS C57BL/6J females received an AIN93G diet with high or low vitamin D from before mating until weaning. Post-weaning, male and female offspring remained on their respective vitamin D level or were switched and fed a high fat and sucrose diet until killing (age 7 months). Bacteroides and Prevotella were quantified in dams' feces and offspring colonic contents. LPS concentrations, bone mineral density and content, strength and structure data were integrated from our previous studies in the same mice. Spearman correlations were completed between Bacteroides and LPS, and bone outcomes. RESULTS There was a maternal vitamin D effect on colonic Bacteroides but not Prevotella (dam diet: <0.001 and 0.735) in adult male offspring, independent of dams fecal Bacteroides before birth (P=0.998). In males, but not females, Bacteroides correlated with LPS (r=-0.488, P=0.018), trabecular femur peak load (r=0.362, P=0.033), vertebral trabecular separation (r=-0.605, P=0.006), trabecular number (r=0.614, P=0.005) and bone volume fraction (r=0.549, P=0.015). CONCLUSIONS Dietary vitamin D programs Bacteroides in male adult offspring only, which correlated negatively with systemic inflammation and positively with bone strength and structure. This may have implications on maternal diet and nutritional guidelines targeting sexes in a different manner.
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Meyer DM, Brei C, Stecher L, Much D, Brunner S, Hauner H. The relationship between breast milk leptin and adiponectin with child body composition from 3 to 5 years: a follow-up study. Pediatr Obes 2017; 12 Suppl 1:125-129. [PMID: 27863153 DOI: 10.1111/ijpo.12192] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2016] [Revised: 08/30/2016] [Accepted: 09/14/2016] [Indexed: 12/27/2022]
Abstract
BACKGROUND Research indicates that breast milk contains bioactive components that influence metabolism in infancy and may play a role in the prevention of obesity in early childhood. In our initial study, 147 breastfeeding mother/child pairs were followed from birth to 2 years of age to examine the relationship between breast milk leptin and total adiponectin (collected at 6 weeks and 4 months postpartum) and infant body composition. Higher breast milk total adiponectin was related to greater fat mass and weight gain in children at 1 and 2 years of age, whereas leptin showed no association. OBJECTIVES/METHODS In this follow-up, we examined the relationship between both adipokines and children's body weight, body mass index percentiles, sum of four skin-folds, percentage of body fat, fat mass and lean body mass at 3, 4 and 5 years of age. RESULTS Breast milk adipokines were largely unrelated to child anthropometric measures. CONCLUSION Our results do not provide significant evidence that breast milk adipokines can predict adiposity in preschool children.
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Affiliation(s)
- D M Meyer
- From the Else Kröner-Fresenius-Center for Nutritional Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - C Brei
- From the Else Kröner-Fresenius-Center for Nutritional Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - L Stecher
- From the Else Kröner-Fresenius-Center for Nutritional Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - D Much
- Institute of Diabetes Research, Helmholtz Zentrum München, Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - S Brunner
- From the Else Kröner-Fresenius-Center for Nutritional Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
| | - H Hauner
- From the Else Kröner-Fresenius-Center for Nutritional Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.,ZIEL - Institute for Food and Health, Nutritional Medicine Unit, Technische Universität München, Freising, Germany
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Nutritional aspects of commercially prepared infant foods in developed countries: a narrative review. Nutr Res Rev 2017; 30:138-148. [DOI: 10.1017/s0954422417000038] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
AbstractNutritional intake during infancy is a critical aspect of child development and health that is of significant public health concern. Although there is extensive research on breast-feeding and timing of solid food introduction, there is less evidence on types of solid foods fed to infants, specifically commercially prepared infant foods. The consumption of commercially prepared infant foods is very prevalent in many developed countries, exceeding the consumption of homemade foods in some situations. Although these food products may have practical advantages, there are concerns about their nutritional composition, sweet taste, bioavailability of micronutrients, diversity of ingredients and long-term health effects. The extent that the manufacturing, fortification and promotion of these products are regulated by legislation varies between countries and regions. The aim of the present narrative review is to investigate, appraise and summarise these aspects. Overall there are very few studies directly comparing homemade and commercial infant foods and a lack of longitudinal studies to draw firm conclusions on whether commercial infant foods are mostly beneficial or unfavourable to infant health.
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Safe S, Li X. Endocrine disruption: Relevance of experimental studies in female animals to human studies. CURRENT OPINION IN TOXICOLOGY 2017; 3:12-19. [DOI: 10.1016/j.cotox.2017.04.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Greathouse KL, Faucher MA, Hastings-Tolsma M. The Gut Microbiome, Obesity, and Weight Control in Women's Reproductive Health. West J Nurs Res 2017; 39:1094-1119. [PMID: 28303750 DOI: 10.1177/0193945917697223] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The microbes residing in the human gut, referred to as the microbiome, are intricately linked to energy homeostasis and subsequently obesity. Integral to the origins of obesity, the microbiome is believed to affect not only health of the human gut but also overall health. This microbiome-obesity association is mediated through the process of energy extraction, metabolism, and cross talk between the brain and the gut microbiome. Host exposures, including diet, that potentially modify genetic predisposition to obesity and affect weight management are reviewed. The higher prevalence of obesity among women and recent evidence linking obesity during pregnancy with offspring health make this topic particularly relevant. Current limitations in microbiome research to address obesity and future advances in this field are described. Applications of this science with respect to applied nursing and overall health care in general are included, with emphasis on the reproductive health of women and their offspring.
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Affiliation(s)
- K Leigh Greathouse
- 1 Robbins College of Health and Human Science, Baylor University, Waco, TX, USA
| | - Mary Ann Faucher
- 2 Louise Harrington School of Nursing, Baylor University, Dallas, TX, USA
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Korpela K, Zijlmans MAC, Kuitunen M, Kukkonen K, Savilahti E, Salonen A, de Weerth C, de Vos WM. Childhood BMI in relation to microbiota in infancy and lifetime antibiotic use. MICROBIOME 2017; 5:26. [PMID: 28253911 PMCID: PMC5335838 DOI: 10.1186/s40168-017-0245-y] [Citation(s) in RCA: 91] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 02/15/2017] [Indexed: 05/21/2023]
Abstract
BACKGROUND Children with high body mass index (BMI) at preschool age are at risk of developing obesity. Early identification of factors that increase the risk of excessive weight gain could help direct preventive actions. The intestinal microbiota and antibiotic use have been identified as potential modulators of early metabolic programming and weight development. To test if the early microbiota composition is associated with later BMI, and if antibiotic use modifies this association, we analysed the faecal microbiota composition at 3 months and the BMI at 5-6 years in two cohorts of healthy children born vaginally at term in the Netherlands (N = 87) and Finland (N = 75). We obtained lifetime antibiotic use records and measured weight and height of all children. RESULTS The relative abundance of streptococci was positively and the relative abundance of bifidobacteria negatively associated with the BMI outcome. The association was especially strong among children with a history of antibiotic use. Bacteroides relative abundance was associated with BMI only in the children with minimal lifetime antibiotic exposure. CONCLUSIONS The intestinal microbiota of infants are predictive of later BMI and may serve as an early indicator of obesity risk. Bifidobacteria and streptococci, which are indicators of microbiota maturation in infants, are likely candidates for metabolic programming of infants, and their influence on BMI appears to depend on later antibiotic use.
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Affiliation(s)
- K. Korpela
- Immunobiology Research Program, Department of Bacteriology and Immunology, University of Helsinki, Haartmaninkatu 3, PO box 21, 00014 Helsinki, Finland
| | - M. A. C. Zijlmans
- Department of Developmental Psychology, Behavioural Science Institute, Radboud University Nijmegen, Nijmegen, The Netherlands
| | - M. Kuitunen
- Children’s Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
| | - K. Kukkonen
- Skin and Allergy Hospital, Department of Paediatrics, Helsinki University Central Hospital, Helsinki, Finland
| | - E. Savilahti
- Children’s Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
| | - A. Salonen
- Immunobiology Research Program, Department of Bacteriology and Immunology, University of Helsinki, Haartmaninkatu 3, PO box 21, 00014 Helsinki, Finland
| | - C. de Weerth
- Department of Developmental Psychology, Behavioural Science Institute, Radboud University Nijmegen, Nijmegen, The Netherlands
| | - W. M. de Vos
- Immunobiology Research Program, Department of Bacteriology and Immunology, University of Helsinki, Haartmaninkatu 3, PO box 21, 00014 Helsinki, Finland
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
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Taylor RW, Heath ALM, Galland BC, Cameron SL, Lawrence JA, Gray AR, Tannock GW, Lawley B, Healey D, Sayers RM, Hanna M, Meredith-Jones K, Hatch B, Taylor BJ. Three-year follow-up of a randomised controlled trial to reduce excessive weight gain in the first two years of life: protocol for the POI follow-up study. BMC Public Health 2016; 16:771. [PMID: 27514714 PMCID: PMC4982410 DOI: 10.1186/s12889-016-3383-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2016] [Accepted: 07/27/2016] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The Prevention of Overweight in Infancy (POI) study was a four-arm randomised controlled trial (RCT) in 802 families which assessed whether additional education and support on sleep (Sleep group); food, physical activity and breastfeeding (FAB group); or both (Combination group), reduced excessive weight gain from birth to 2 years of age, compared to usual care (Control group). The study had high uptake at recruitment (58 %) and retention at 2 years (86 %). Although the FAB intervention produced no significant effect on BMI or weight status at 2 years, the odds of obesity were halved in those who received the sleep intervention, despite no apparent effect on sleep duration. We speculate that enhanced self-regulatory behaviours may exist in the Sleep group. Self-regulation was not measured in our initial intervention, but extensive measures have been included in this follow-up study. Thus, the overall aim of the POI follow-up is to determine the extent to which augmented parental support and education on infant sleep, feeding, diet, and physical activity in the first 2 years of life reduces BMI at 3.5 and 5 years of age, and to determine the role of self-regulation in any such relationship. METHODS/DESIGN We will contact all 802 families and seek renewed consent to participate in the follow-up study. The families have received no POI intervention since the RCT finished at 2 years of age. Follow-up data collection will occur when the children are aged 3.5 and 5 years (i.e. up to 3 years post-intervention). Outcomes of interest include child anthropometry, body composition (DXA scan), diet (validated food frequency questionnaire), physical activity (accelerometry), sleep (questionnaire and accelerometry), and self-regulation (questionnaires and neuropsychological assessment). DISCUSSION Our follow-up study has been designed primarily to enable us to determine whether the intriguing benefit of the sleep intervention suggested at 2 years of age remains as children approach school age. However, cohort analyses will also investigate how BMI, self-regulation, and sleep consolidation develop during the early years. This information will be valuable to researchers and policy makers progressing the field of early childhood obesity prevention. TRIAL REGISTRATION ClinicalTrials.gov number NCT00892983 .
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Affiliation(s)
- Rachael W. Taylor
- Department of Medicine, University of Otago, PO Box 56, Dunedin, 9054 New Zealand
| | | | - Barbara C. Galland
- Department of Women’s and Children’s Health, University of Otago, Dunedin, New Zealand
| | - Sonya L. Cameron
- Department of Women’s and Children’s Health, University of Otago, Dunedin, New Zealand
| | - Julie A. Lawrence
- Department of Women’s and Children’s Health, University of Otago, Dunedin, New Zealand
| | - Andrew R. Gray
- Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand
| | - Gerald W. Tannock
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
| | - Blair Lawley
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
| | - Dione Healey
- Department of Psychology, University of Otago, Dunedin, New Zealand
| | - Rachel M. Sayers
- Department of Women’s and Children’s Health, University of Otago, Dunedin, New Zealand
| | - Maha Hanna
- Department of Women’s and Children’s Health, University of Otago, Dunedin, New Zealand
| | - Kim Meredith-Jones
- Department of Medicine, University of Otago, PO Box 56, Dunedin, 9054 New Zealand
| | - Burt Hatch
- Department of Women’s and Children’s Health, University of Otago, Dunedin, New Zealand
| | - Barry J. Taylor
- Department of Women’s and Children’s Health, University of Otago, Dunedin, New Zealand
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Abstract
The human body is host to a vast number of microbes, including bacterial, fungal and protozoal microoganisms, which together constitute our microbiota. Evidence is emerging that the intestinal microbiome is intrinsically linked with overall health, including obesity risk. Obesity and obesity-related metabolic disorders are characterized by specific alterations in the composition and function of the human gut microbiome. Mechanistic studies have indicated that the gastrointestinal microbiota can influence both sides of the energy balance equation; namely, as a factor influencing energy utilization from the diet and as a factor that influences host genes that regulate energy expenditure and storage. Moreover, its composition is not fixed and can be influenced by several dietary components. This fact raises the attractive possibility that manipulating the gut microbiota could facilitate weight loss or prevent obesity in humans. Emerging as possible strategies for obesity prevention and/or treatment are targeting the microbiota, in order to restore or modulate its composition through the consumption of live bacteria (probiotics), nondigestible or limited digestible food constituents such as oligosaccharides (prebiotics), or both (synbiotics), or even fecal transplants.
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Woo Baidal JA, Locks LM, Cheng ER, Blake-Lamb TL, Perkins ME, Taveras EM. Risk Factors for Childhood Obesity in the First 1,000 Days: A Systematic Review. Am J Prev Med 2016; 50:761-779. [PMID: 26916261 DOI: 10.1016/j.amepre.2015.11.012] [Citation(s) in RCA: 627] [Impact Index Per Article: 69.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Revised: 11/17/2015] [Accepted: 11/18/2015] [Indexed: 12/27/2022]
Abstract
CONTEXT Mounting evidence suggests that the origins of childhood obesity and related disparities can be found as early as the "first 1,000 days"-the period from conception to age 2 years. The main goal of this study is to systematically review existing evidence for modifiable childhood obesity risk factors present from conception to age 2 years. EVIDENCE ACQUISITION PubMed, Embase, and Web of Science were searched for studies published between January 1, 1980, and December 12, 2014, of childhood obesity risk factors present during the first 1,000 days. Prospective, original human subject, English-language research with exposure occurrence during the first 1,000 days and with the outcome of childhood overweight or obesity (BMI ≥85th percentile for age and sex) collected between age 6 months and 18 years were analyzed between December 13, 2014, and March 15, 2015. EVIDENCE SYNTHESIS Of 5,952 identified citations, 282 studies met inclusion criteria. Several risk factors during the first 1,000 days were consistently associated with later childhood obesity. These included higher maternal pre-pregnancy BMI, prenatal tobacco exposure, maternal excess gestational weight gain, high infant birth weight, and accelerated infant weight gain. Fewer studies also supported gestational diabetes, child care attendance, low strength of maternal-infant relationship, low SES, curtailed infant sleep, inappropriate bottle use, introduction of solid food intake before age 4 months, and infant antibiotic exposure as risk factors for childhood obesity. CONCLUSIONS Modifiable risk factors in the first 1,000 days can inform future research and policy priorities and intervention efforts to prevent childhood obesity.
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Affiliation(s)
- Jennifer A Woo Baidal
- Division of General Academic Pediatrics, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts; Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Columbia University Medical Center, New York City, New York
| | - Lindsey M Locks
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
| | - Erika R Cheng
- Division of General Academic Pediatrics, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts
| | - Tiffany L Blake-Lamb
- Department of Obstetrics and Gynecology, Massachusetts General Hospital, Boston, Massachusetts; Kraft Center for Community Health Leadership, Partners Healthcare, Boston, Massachusetts
| | - Meghan E Perkins
- Division of General Academic Pediatrics, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts
| | - Elsie M Taveras
- Division of General Academic Pediatrics, Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
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Kim KE, Cho YS, Baek KS, Li L, Baek KH, Kim JH, Kim HS, Sheen YH. Lipopolysaccharide-binding protein plasma levels as a biomarker of obesity-related insulin resistance in adolescents. KOREAN JOURNAL OF PEDIATRICS 2016; 59:231-8. [PMID: 27279888 PMCID: PMC4897159 DOI: 10.3345/kjp.2016.59.5.231] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 11/01/2015] [Accepted: 12/02/2015] [Indexed: 12/29/2022]
Abstract
Purpose Lipopolysaccharide-binding protein (LBP) is a 65-kDa acute phase protein, derived from the liver, which is present in high concentrations in plasma. Data regarding the association between circulating plasma LBP levels and obesity-related biomarkers in the pediatric population are scarce. We aimed to determine whether there was a difference in plasma LBP levels between overweight/obese and normal-weight adolescents and to assess the correlation of circulating LBP levels with anthropometric measures and obesity-related biomarkers, including insulin resistance, liver enzyme levels, and lipid profiles. Methods The study included 87 adolescents aged 12–13 years; 44 were overweight/obese and 43 were of normal-weight. We assessed anthropometric and laboratory measures, including body mass index (BMI), blood pressure, insulin resistance, liver enzyme levels, and lipid profiles. Plasma LBP levels were measured using an enzyme-linked immunosorbent assay. Results The mean age of the participants was 12.9±0.3 years. Circulating plasma LBP levels were significantly increased in overweight/obese participants compared with those in normal-weight participants (7.8±1.9 µg/mL vs. 6.0±1.6 µg/mL, P<0.001). LBP levels were significantly and positively associated with BMI, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, total cholesterol, low density lipoprotein-cholesterol, fasting glucose and insulin, and insulin resistance as indicated by the homeostatic model assessment of insulin resistance (HOMA-IR) (all P<0.05). In multivariate linear regression analysis, BMI and HOMA-IR were independently and positively associated with plasma LBP levels. Conclusion LBP is an inflammatory biomarker associated with BMI and obesity-related insulin resistance in adolescents. The positive correlation between these parameters suggests a potentially relevant pathophysiological mechanism linking LBP to obesity-related insulin resistance in adolescents.
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Affiliation(s)
- Ki Eun Kim
- Department of Pediatrics, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea
| | - Young Sun Cho
- Department of Pediatrics, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Kyung Suk Baek
- Department of Pediatrics, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea
| | - Lan Li
- Department of Biomedical Science, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Kwang-Hyun Baek
- Department of Biomedical Science, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Jung Hyun Kim
- Atmin Radiology and Health Promotion Center, Seoul, Korea
| | - Ho-Seong Kim
- Department of Pediatrics, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Youn Ho Sheen
- Department of Pediatrics, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, Korea
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Cassidy-Bushrow AE, Havstad S, Basu N, Ownby DR, Park SK, Ownby DR, Johnson CC, Wegienka G. Detectable Blood Lead Level and Body Size in Early Childhood. Biol Trace Elem Res 2016; 171:41-7. [PMID: 26358768 PMCID: PMC4788572 DOI: 10.1007/s12011-015-0500-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Accepted: 08/28/2015] [Indexed: 12/18/2022]
Abstract
Rates of childhood obesity have risen at the same time rates of high blood lead levels (BLLs) have fallen. Recent studies suggest that higher BLL is inversely associated with body size in older children (ages 3-19 years). No contemporaneous studies have examined if having a detectable BLL is associated with body size in very early childhood. We examined if detectable BLL is associated with body size in early childhood. A total of 299 birth cohort participants completed a study visit at ages 2-3 years with weight and height measurements; prior to this clinic visit, a BLL was drawn as part of routine clinical care. Body mass index (BMI) percentile and Z-score were calculated; children with BMI ≥85th percentile were considered overweight/obese at age of 2 years. Detectable BLL was defined as BLL ≥1 μg/dL. A total of 131 (43.8 %) children had a detectable BLL measured at mean aged 15.4 ± 5.5 months. Mean age at body size assessment was 2.2 ± 0.3 years (53.2 % male, 68.6 % African-American). After adjusting for race, sex, and birth weight, children with a detectable BLL had a 43 % lower risk of BMI ≥85th percentile (P = 0.041) and a 0.35-unit lower BMI Z-score (P = 0.008) compared to children without a detectable BLL. Neither race nor sex modified this association (all interactions P > 0.21). Consistent with recent studies in older children, having a detectable BLL was associated with smaller body size at ages 2-3 years. Additional research on the mechanism of this association is needed but may include mechanisms of appetite suppression via lead.
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Affiliation(s)
- Andrea E Cassidy-Bushrow
- Department of Public Health Sciences, Henry Ford Hospital, One Ford Place, 5C, Detroit, MI, 48202, USA.
- Center for Allergy, Asthma and Immunology Research, Henry Ford Hospital, Detroit, MI, USA.
| | - Suzanne Havstad
- Department of Public Health Sciences, Henry Ford Hospital, One Ford Place, 5C, Detroit, MI, 48202, USA
- Center for Allergy, Asthma and Immunology Research, Henry Ford Hospital, Detroit, MI, USA
| | - Niladri Basu
- Agricultural and Environmental Sciences, McGill University, Montreal, Quebec, Canada
- Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA
| | - David R Ownby
- Department of Chemistry, Towson University, Towson, MD, USA
| | - Sung Kyun Park
- Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA
- Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA
| | - Dennis R Ownby
- Center for Allergy, Asthma and Immunology Research, Henry Ford Hospital, Detroit, MI, USA
- Division of Allergy and Clinical Immunology, Department of Pediatrics, Georgia Regents University, Augusta, GA, USA
| | - Christine Cole Johnson
- Department of Public Health Sciences, Henry Ford Hospital, One Ford Place, 5C, Detroit, MI, 48202, USA
- Center for Allergy, Asthma and Immunology Research, Henry Ford Hospital, Detroit, MI, USA
| | - Ganesa Wegienka
- Department of Public Health Sciences, Henry Ford Hospital, One Ford Place, 5C, Detroit, MI, 48202, USA
- Center for Allergy, Asthma and Immunology Research, Henry Ford Hospital, Detroit, MI, USA
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45
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Cassidy-Bushrow AE, Wegienka G, Havstad S, Levin AM, Lynch SV, Ownby DR, Rundle AG, Woodcroft KJ, Zoratti EM, Johnson CC. Does pet-keeping modify the association of delivery mode with offspring body size? Matern Child Health J 2016; 19:1426-33. [PMID: 25427878 DOI: 10.1007/s10995-014-1649-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Caesarean-section (CS) delivery increases risk of childhood obesity, and is associated with a distinct early-life gut microbiome, which may contribute to obesity. Household pets may alter human gut microbiome composition. We examined if pet-keeping modified the association of CS with obesity at age 2 years in 639 Wayne County Health, Environment, Allergy and Asthma Longitudinal Study birth cohort participants. Pet-keeping was defined as having a dog or cat (indoors ≥1 h/day) at child age 2 years. We used logistic regression to test for an interaction between CS and pet-keeping with obesity (BMI ≥ 95th percentile) at age 2 years, adjusted for maternal obesity. A total of 328 (51.3 %) children were male; 367 (57.4 %) were African American; 228 (35.7 %) were born by CS; and 55 (8.6 %) were obese. After adjusting for maternal obesity, CS-born children had a non-significant (P = 0.25) but elevated 1.4 (95 % CI 0.8, 2.5) higher odds of obesity compared to those born vaginally. There was evidence of effect modification between current pet-keeping and delivery mode with obesity at age 2 years (interaction P = 0.054). Compared to children born vaginally without a pet currently in the home, children born via CS without a pet currently in the home had a statistically significant (P = 0.043) higher odds (odds ratio 2.00; 95 % CI 1.02, 3.93) of being obese at age 2 years. Pets modified the CS-BMI relationship; whether the underlying mechanism is through effects on environmental or gut microbiome requires specific investigation.
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Affiliation(s)
- Andrea E Cassidy-Bushrow
- Department of Public Health Sciences, Henry Ford Hospital, 1 Ford Place, 5C, Detroit, MI, 48202, USA,
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Grigorescu I, Dumitrascu D. IMPLICATION OF GUT MICROBIOTA IN DIABETES MELLITUS AND OBESITY. ACTA ENDOCRINOLOGICA (BUCHAREST, ROMANIA : 2005) 2016; 12:206-214. [PMID: 31149088 PMCID: PMC6535288 DOI: 10.4183/aeb.2016.206] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Differences in the composition of the species of microorganisms in the gut may predict the evolution toward obesity and diabetes mellitus. We carried out a systematic review of the studies dedicated to the role of gut microbiota in diabetes mellitus and obesity. METHODS A systematic literature search of electronic databases was performed, using the search syntax: "Gut microbiota and diabetes and obesity"; abstracts in English, with data about mechanisms of pathogenesis and treatment options by changing the gut composition were included (259 articles). Studies were excluded if they did not have an abstract, or they contained no data about the exact implication mechanism of microbiota. RESULTS There are differences regarding the composition of the gut microbiota in healthy people and type 2 diabetes mellitus patients; the later proved to have significantly decreased Clostridium components, and increased Lactobacillus and Bifidobacterium populations.The intestines of obese subjects are less rich in microbial genes, have a reduced amount of Bacteroidetes and an increased amount of Firmicutes. Fecal microbiota transplantation from obese subjects resulted in adoption of the donor somatotype. Early differences in gut microbiota composition (higher number of Bifidobacteria) function as diagnostic markers for the development of type 2 diabetes mellitus in high-risk patients.The gut endotoxins contribute to metabolic syndrome manifestation. Experimental studies with prebiotic showed lower levels of cytokines and antiobesity potential. CONCLUSION Microbiota composition and its changes since childhood have an important role in the metabolic syndrome. Any intervention in order to prevent or treat obesity and diabetes mellitus should have as target the gut immune system.
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Affiliation(s)
- I. Grigorescu
- “Iuliu Haţieganu” University of Medicine and Pharmacy, 2 Medical Department, Cluj-Napoca, Romania
| | - D.L. Dumitrascu
- “Iuliu Haţieganu” University of Medicine and Pharmacy, 2 Medical Department, Cluj-Napoca, Romania
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47
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Madan JC, Hoen AG, Lundgren SN, Farzan SF, Cottingham KL, Morrison HG, Sogin ML, Li H, Moore JH, Karagas MR. Association of Cesarean Delivery and Formula Supplementation With the Intestinal Microbiome of 6-Week-Old Infants. JAMA Pediatr 2016; 170:212-9. [PMID: 26752321 PMCID: PMC4783194 DOI: 10.1001/jamapediatrics.2015.3732] [Citation(s) in RCA: 191] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
IMPORTANCE The intestinal microbiome plays a critical role in infant development, and delivery mode and feeding method (breast milk vs formula) are determinants of its composition. However, the importance of delivery mode beyond the first days of life is unknown, and studies of associations between infant feeding and microbiome composition have been generally limited to comparisons between exclusively breastfed and formula-fed infants, with little consideration given to combination feeding of both breast milk and formula. OBJECTIVE To examine the associations of delivery mode and feeding method with infant intestinal microbiome composition at approximately 6 weeks of life. DESIGN, SETTING, AND PARTICIPANTS Prospective observational study of 102 infants followed up as part of a US pregnancy cohort study. EXPOSURES Delivery mode was abstracted from delivery medical records, and feeding method prior to the time of stool collection was ascertained through detailed questionnaires. MAIN OUTCOMES AND MEASURES Stool microbiome composition was characterized using next-generation sequencing of the 16S rRNA gene. RESULTS There were 102 infants (mean gestational age, 39.7 weeks; range, 37.1-41.9 weeks) included in this study, of whom 70 were delivered vaginally and 32 by cesarean delivery. In the first 6 weeks of life, 70 were exclusively breastfed, 26 received combination feeding, and 6 were exclusively formula fed. We identified independent associations between microbial community composition and both delivery mode (P< .001; Q < .001) and feeding method (P = .01; Q < .001). Differences in microbial community composition between vaginally delivered infants and infants delivered by cesarean birth were equivalent to or significantly larger than those between feeding groups (P = .003). Bacterial communities associated with combination feeding were more similar to those associated with exclusive formula feeding than exclusive breastfeeding (P = .002). We identified 6 individual bacterial genera that were differentially abundant between delivery mode and feeding groups. CONCLUSIONS AND RELEVANCE The infant intestinal microbiome at approximately 6 weeks of age is significantly associated with both delivery mode and feeding method, and the supplementation of breast milk feeding with formula is associated with a microbiome composition that resembles that of infants who are exclusively formula fed. These results may inform feeding choices and shed light on the mechanisms behind the lifelong health consequences of delivery and infant feeding modalities.
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Affiliation(s)
- Juliette C. Madan
- Division of Neonatology, Department of Pediatrics, Children’s Hospital at Dartmouth, Lebanon, NH, USA,Children’s Environmental Health & Disease Prevention Research Center at Dartmouth, Hanover, New Hampshire, USA
| | - Anne G. Hoen
- Children’s Environmental Health & Disease Prevention Research Center at Dartmouth, Hanover, New Hampshire, USA,Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, USA,Computational Genetics Laboratory, Geisel School of Medicine at Dartmouth, Hanover, NH, USA,Corresponding author: Anne G. Hoen, PhD, Department of Epidemiology, Geisel School of Medicine at Dartmouth. 1 Medical Center Drive, Lebanon, NH 03756. 603-653-6087.
| | - Sara N. Lundgren
- Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - Shohreh F. Farzan
- Children’s Environmental Health & Disease Prevention Research Center at Dartmouth, Hanover, New Hampshire, USA,Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, USA
| | - Kathryn L. Cottingham
- Children’s Environmental Health & Disease Prevention Research Center at Dartmouth, Hanover, New Hampshire, USA,Department of Biological Sciences, Dartmouth College, Hanover, NH, USA
| | - Hilary G. Morrison
- Josephine Bay Paul Center, Marine Biological Laboratory, Woods Hole, MA, USA
| | - Mitchell L. Sogin
- Josephine Bay Paul Center, Marine Biological Laboratory, Woods Hole, MA, USA
| | - Hongzhe Li
- Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Jason H. Moore
- Computational Genetics Laboratory, Geisel School of Medicine at Dartmouth, Hanover, NH, USA,Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Margaret R. Karagas
- Children’s Environmental Health & Disease Prevention Research Center at Dartmouth, Hanover, New Hampshire, USA,Department of Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, USA,Center for Molecular Epidemiology, The Geisel School of Medicine at Dartmouth, Hanover, NH, USA
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48
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Cassidy-Bushrow AE, Wegienka G, Havstad S, Levin AM, Lynch SV, Ownby DR, Rundle AG, Woodcroft KJ, Zoratti EM, Johnson CC. Race-specific Association of Caesarean-Section Delivery with Body Size at Age 2 Years. Ethn Dis 2016; 26:61-8. [PMID: 26843797 DOI: 10.18865/ed.26.1.61] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
OBJECTIVE African American children are at higher risk of obesity than White children and African American women are more likely to undergo caesarean-section (CS) delivery than White women. CS is associated with childhood obesity; however, little is known whether this relationship varies by race. We examined if the association of CS with obesity at age 2 years varied by race. DESIGN Longitudinal birth cohort. SETTING Birth cohort conducted in a health care system in metropolitan Detroit, Michigan with follow-up at age 2 years. PARTICIPANTS 639 birth cohort participants; 367 children (57.4%) were born to African American mothers and 230 (36.0%) children were born via CS. MAIN OUTCOME MEASURES Obesity defined as body mass index ≥95th percentile at age 2 years. RESULTS Slightly more children of African American (n=37; 10.1%) than non-African American mothers (n=18; 6.6%) were obese (P=.12). There was evidence of effect modification between race and delivery mode with obesity at age 2 years (interaction P=.020). In children of African American mothers, CS compared to vaginal birth was associated with a significantly higher odds of obesity (aOR=2.35 (95% CI: 1.16, 4.77), P=.017). In contrast, delivery mode was not associated with obesity at age 2 years in children of non-African American mothers (aOR=.47 (95% CI: .13, 1.71), P=.25). CONCLUSIONS There is evidence for a race-specific effect of CS on obesity at age 2 years; potential underlying mechanisms may be racial differences in the developing gut microbiome or in epigenetic programming. Future research is needed to determine if this racial difference persists into later childhood.
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Affiliation(s)
| | - Ganesa Wegienka
- Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan
| | - Suzanne Havstad
- Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan
| | - Albert M Levin
- Department of Public Health Sciences, Henry Ford Hospital, Detroit, Michigan
| | - Susan V Lynch
- Department of Medicine, University of California, San Francisco
| | - Dennis R Ownby
- Division of Allergy and Clinical Immunology, Department of Pediatrics, Georgia Regents University, Augusta, Georgia
| | - Andrew G Rundle
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York
| | | | - Edward M Zoratti
- Division of Allergy and Clinical Immunology, Henry Ford Hospital, Detroit, Michigan
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49
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Dogra S, Sakwinska O, Soh SE, Ngom-Bru C, Brück WM, Berger B, Brüssow H, Karnani N, Lee YS, Yap F, Chong YS, Godfrey KM, Holbrook JD. Rate of establishing the gut microbiota in infancy has consequences for future health. Gut Microbes 2015; 6:321-5. [PMID: 26516657 PMCID: PMC4826121 DOI: 10.1080/19490976.2015.1078051] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
The gut of the human neonate is colonized rapidly after birth from an early sparse and highly distinct microbiota to a more adult-like and convergent state, within 1 to 3 years. The progression of colonizing bacterial species is non-random. During the first months of life several shifts commonly occur in the species prevalent in our guts. Although the sequential progression of these species is remarkably consistent across individuals and geographies, there is inter-individual variation in the rate of progression. Our study and others suggest that the rate is influenced by environmental factors, and influences our future health. In this article, we review our recent contribution to cataloging the developing infant gut microbiota alongside other important recent studies. We suggest testable hypotheses that arise from this synthesis.
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Affiliation(s)
- Shaillay Dogra
- Singapore Institute for Clinical Sciences (SICS); Agency for Science and Technology Research (A*STAR); Singapore
| | | | - Shu-E Soh
- Department of Pediatrics; Yong Loo Lin School of Medicine; National University of Singapore; Singapore
| | | | | | | | | | - Neerja Karnani
- Singapore Institute for Clinical Sciences (SICS); Agency for Science and Technology Research (A*STAR); Singapore
| | - Yung Seng Lee
- Singapore Institute for Clinical Sciences (SICS); Agency for Science and Technology Research (A*STAR); Singapore,Department of Pediatrics; Yong Loo Lin School of Medicine; National University of Singapore; Singapore
| | - Fabian Yap
- KK Women's and Children's Hospital; Singapore
| | - Yap-Seng Chong
- Singapore Institute for Clinical Sciences (SICS); Agency for Science and Technology Research (A*STAR); Singapore,Department of Obstetrics and Gynecology; Yong Loo Lin School of Medicine; National University of Singapore; Singapore
| | - Keith M Godfrey
- MRC Lifecourse Epidemiology Unit and NIHR Southampton Biomedical Research Centre; University of Southampton and University Hospital Southampton NHS Foundation Trust; Southampton, United Kingdom
| | - Joanna D Holbrook
- Singapore Institute for Clinical Sciences (SICS); Agency for Science and Technology Research (A*STAR); Singapore,Correspondence to: Joanna D Holbrook;
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50
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Hoen AG, Li J, Moulton LA, O’Toole GA, Housman ML, Koestler DC, Guill MF, Moore JH, Hibberd PL, Morrison HG, Sogin ML, Karagas MR, Madan JC. Associations between Gut Microbial Colonization in Early Life and Respiratory Outcomes in Cystic Fibrosis. J Pediatr 2015; 167:138-47.e1-3. [PMID: 25818499 PMCID: PMC4674690 DOI: 10.1016/j.jpeds.2015.02.049] [Citation(s) in RCA: 115] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2014] [Revised: 01/28/2015] [Accepted: 02/18/2015] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To examine patterns of microbial colonization of the respiratory and intestinal tracts in early life in infants with cystic fibrosis (CF) and their associations with breastfeeding and clinical outcomes. STUDY DESIGN A comprehensive, prospective longitudinal analysis of the upper respiratory and intestinal microbiota in a cohort of infants and young children with CF followed from birth was performed. Genus-level microbial community composition was characterized using 16S-targeted pyrosequencing, and relationships with exposures and outcomes were assessed using linear mixed-effects models, time-to-event analysis, and principal components analysis. RESULTS Sequencing of 120 samples from 13 subjects collected from birth to 34 months revealed relationships between breastfeeding, microbial diversity in the respiratory and intestinal tracts, and the timing of onset of respiratory complications, including exacerbations and colonization with Pseudomonas aeruginosa. Fluctuations in the abundance of specific bacterial taxa preceded clinical outcomes, including a significant decrease in bacteria of the genus Parabacteroides within the intestinal tract prior to the onset of chronic P aeruginosa colonization. Specific assemblages of bacteria in intestinal samples, but not respiratory samples, were associated with CF exacerbation in early life, indicating that the intestinal microbiome may play a role in lung health. CONCLUSIONS Our findings relating breastfeeding to respiratory outcomes, gut diversity to prolonged periods of health, and specific bacterial communities in the gut prior to respiratory complications in CF highlight a connection between the intestinal microbiome and health and point to potential opportunities for antibiotic or probiotic interventions. Further studies in larger cohorts validating these findings are needed.
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Affiliation(s)
- Anne G. Hoen
- Computational Genetics Laboratory, Institute for Quantitative Biomedical Sciences, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH 03755,Department of Epidemiology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH 03755
| | - Jing Li
- Computational Genetics Laboratory, Institute for Quantitative Biomedical Sciences, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH 03755
| | - Lisa A. Moulton
- Division of Allergy and Pediatric Pulmonology, Department of Pediatrics, Dartmouth Hitchcock Medical Center, Lebanon NH 03756
| | - George A. O’Toole
- Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755
| | - Molly L. Housman
- Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755
| | - Devin C. Koestler
- Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS 66160
| | - Margaret F. Guill
- Division of Allergy and Pediatric Pulmonology, Department of Pediatrics, Dartmouth Hitchcock Medical Center, Lebanon NH 03756
| | - Jason H. Moore
- Computational Genetics Laboratory, Institute for Quantitative Biomedical Sciences, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH 03755
| | - Patricia L. Hibberd
- Division of Global Health, Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114
| | - Hilary G. Morrison
- Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, MA 02543
| | - Mitchell L. Sogin
- Josephine Bay Paul Center for Comparative Molecular Biology and Evolution, Marine Biological Laboratory, Woods Hole, MA 02543
| | - Margaret R. Karagas
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, NH 03755
| | - Juliette C. Madan
- Division of Neonatology, Department of Pediatrics, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756
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