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Mirzohreh ST, Sohrabnavi A, Panahi P, Nikniaz Z, Farhangi MA, Daneghian S, Nikniaz L. Effect of prebiotics on growth metrics in infants: A GRADE approach systematic review and meta-analysis of randomized clinical trials. Nutr Res 2025; 137:22-46. [PMID: 40215676 DOI: 10.1016/j.nutres.2025.03.003] [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: 08/17/2024] [Revised: 03/06/2025] [Accepted: 03/06/2025] [Indexed: 05/02/2025]
Abstract
Breastfeeding is often not feasible for all mothers, making infant formula a critical alternative for ensuring infant safety and nutrition. We hypothesized that the inclusion of prebiotics in infant formula significantly affects growth metrics in infants compared to standard formula. This study aims to fill a knowledge gap regarding the effects of prebiotics in infant formula on infant growth and development, particularly given the varying compositions and durations of prebiotic supplementation. A systematic review was conducted following PRISMA guidelines, analyzing 24 studies sourced from databases such as PubMed and Cochrane, with risk of bias assessed using RoB-2 for randomized controlled trials (RCTs). The findings revealed no significant differences in weight gain (WG), height gain (HG), or head circumference gain (HCG) between prebiotic-fed infants and control groups overall. However, infants receiving prebiotics for 3 or more months exhibited a significant decrease in WG compared to controls (SMD -0.479, P < .05). Notably, those fed formulas containing fructo-oligosaccharides/galacto-oligosaccharides and a combination of polydextrose/galacto-oligosaccharides/lactulose demonstrated improved WG (SMDs of 0.214 and 0.184, P < .05 respectively). Conversely, infants on formulas with inulin-enriched oligo-fructose (IOF) experienced reduced WG and HG. In conclusion, while prebiotics did not consistently enhance growth metrics, specific combinations showed potential benefits, emphasizing the need for tailored approaches in infant formula design to optimize growth without compromising health.
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Affiliation(s)
| | - Asma Sohrabnavi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Padideh Panahi
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Zeinab Nikniaz
- Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahdieh Abbasalizad Farhangi
- Department of Community Medicine, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sevana Daneghian
- Food and Beverages Safety Research Center, Urmia University of medical sciences, Urmia, Iran; Department of nutrition, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Leila Nikniaz
- Tabriz Health Services Management Research Center, Health Management and Safety Promotion Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
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Kebbe M, Leung K, Perrett B, Reimer RA, Adamo K, Redman LM. Effects of Infant Formula Supplemented With Prebiotics on the Gut Microbiome, Gut Environment, Growth Parameters, and Safety and Tolerance: A Systematic Review and Meta-Analysis. Nutr Rev 2025; 83:422-447. [PMID: 39832301 PMCID: PMC11819492 DOI: 10.1093/nutrit/nuae184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2025] Open
Abstract
CONTEXT Prebiotics are often added to infant formulas to mimic the benefits of oligosaccharides found in human milk. OBJECTIVE This systematic review and meta-analysis evaluated the effects of prebiotic-supplemented cow's milk-based formula on the gut microbiota, gut environment, growth parameters, and safety and tolerance in infants ≤6 months old, compared with a standard formula or human milk comparator. DATA SOURCES Searches were performed in the PubMed, Embase, Cochrane Central Register of Controlled Trials, and ProQuest Dissertations & Theses databases. Articles were included that reported on randomized controlled trials, were published from inception until April 2024, and met prespecified inclusion and exclusion criteria. DATA EXTRACTION Outcomes included gut microbiota (eg, diversity; taxa at phylum, family, genus and species levels), gut environment (eg, pH, secretory immunoglobulin A, fecal calprotectin, fecal metabolites), growth parameters (eg, z scores), and safety and tolerance. Fixed or random effects models were used and mean differences (MDs) with 95% CIs were calculated to assess pooled effects. Risk of bias was assessed using the Cochrane Collaboration Tool (RoB 2). DATA ANALYSIS A total of 30 articles met inclusion criteria, with 5290 infants included. Whereas effects on Lactobacillus were inconsistent, prebiotic formula supplementation increased Bifidobacterium counts (k = 7 [MD: 0.49; 95% CI, 0.27-0.71]; I2 = 13%; P < .00001) and decreased fecal pH (k = 7 [MD: -0.39; 95% CI, -0.57 to -0.20]; I2 = 0%; P < .0001) compared with standard formula. Prebiotic formula supplementation increased total bacteria compared with human milk (MD: 0.41 [95% CI, 0.17-0.65]; I2 = 8%; P = .0006). In terms of growth parameters, weight-for-age z scores favored the prebiotic formula group compared with the human milk group (k = 2 [MD: 0.23; 95% CI, 0.04-0.42]; I2 = 7%; P = .02). CONCLUSIONS Prebiotic supplementation in infant formula can positively alter the gut microbiota, particularly Bifidobacterium, without negative impacts on growth. Standardized, high-quality research is needed to confirm the study findings and inform guidelines for prebiotic use in infant nutrition. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42021253589.
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Affiliation(s)
- Maryam Kebbe
- Faculty of Kinesiology, University of New Brunswick, Fredericton, NB E3B 5A3, Canada
| | - Kennedy Leung
- Department of Microbiology and Immunology, McGill University, Montréal, QC H3A 2B4, Canada
| | - Ben Perrett
- Faculty of Kinesiology, University of New Brunswick, Fredericton, NB E3B 5A3, Canada
| | - Raylene A Reimer
- Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 4V8, Canada
| | - Kristi Adamo
- School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, ON K1S 5S9, Canada
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Leanne M Redman
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, United States
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Kadim M, Darma A, Kartjito MS, Dilantika C, Basrowi RW, Sungono V, Jo J. Gastrointestinal Health and Immunity of Milk Formula Supplemented with a Prebiotic Mixture of Short-Chain Galacto-oligosaccharides and Long-Chain Fructo-Oligosaccharides (9:1) in Healthy Infants and Toddlers: A Systematic Review with Meta-Analysis. Pediatr Gastroenterol Hepatol Nutr 2025; 28:1-18. [PMID: 39839466 PMCID: PMC11745571 DOI: 10.5223/pghn.2025.28.1.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 10/03/2024] [Indexed: 01/23/2025] Open
Abstract
Prebiotics are substrates selectively utilized by microorganisms to confer health benefits to their hosts. Various prebiotics have been supplemented in standard milk formulas for infants who cannot be exclusively breastfed, aiming to provide benefits similar to those of breast milk. One of the most commonly used prebiotics is a mixture of 90% short-chain galacto-oligosaccharides and 10% long-chain fructo-oligosaccharides (scGOS/lcFOS [9:1]). Systematic review and meta-analysis were conducted to determine the effectiveness of scGOS:lcFOS (9:1) supplementation in standard milk formula for improving gastrointestinal health and immunity among healthy infants and toddlers, using parameters such as stool pH and intestinal colonization with beneficial bacteria. This systematic review was prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Randomized clinical trials comparing scGOS/lcFOS (9:1)-supplemented formula versus placebo- or non-supplemented formula milk were eligible for inclusion. Related studies on gastrointestinal health and immunity among healthy infants up to five years old were searched from the earliest available date until February 29, 2024. Eighteen publications (number of participants=1,675) were selected for the systematic review, of which 11 were subsequently subjected to a meta-analysis. Results showed that the standard formula supplemented with scGOS/lcFOS (9:1) was well tolerated and conferred various gastrointestinal health and immunity to healthy infants and toddlers. These findings support the supplementation of standard milk formula with scGOS/lcFOS (9:1) for healthy infants and toddlers.
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Affiliation(s)
- Muzal Kadim
- Cipto Mangunkusumo Hospital, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Andy Darma
- Department of Child Health, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
- Department of Child Health, Faculty of Medicine, University of Airlangga, Surabaya, Indonesia
| | | | | | | | - Veli Sungono
- Faculty of Medicine, University of Pelita Harapan, Tangerang, Indonesia
| | - Juandy Jo
- Department of Biology, Faculty of Health Sciences, University of Pelita Harapan, Tangerang, Indonesia
- Mochtar Riady Institute for Nanotechnology, Tangerang, Indonesia
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Qian J, Fang Z, Chang S, Zeng Z, Zhang J. Effectiveness and safety study of formula containing probiotics, prebiotics, synbiotics on fullterm infants' growth - a systematic review and meta-analysis of randomized controlled study. Eur J Clin Nutr 2024:10.1038/s41430-024-01506-9. [PMID: 39448812 DOI: 10.1038/s41430-024-01506-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 08/29/2024] [Accepted: 09/02/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND AND OBJECTIVE Probiotics, prebiotics, and synbiotics, are hot topics of research and have been shown to improve the body's disease state and promote health. Analysis of whether infant formula containing probiotcs, prebiotics, synbiotics is beneficial to infant and child growth. METHODS We systematically searched multiple electronic databases (PubMed, Web of Science, The Cochrane Library, Embase) to identify eligible studies published from 1966 to December 25, 2022. Included studies were randomized controlled trials (RCTs) studying the influence of milk powder containing probiotcs, prebiotics, synbiotics on infants and children's growth. RevMan 5.4 was used to analyze the data. RESULTS A total of 55 RCTs with a total sample size of 8868 participants met the inclusion criteria. Milk powder with probiotics, prebiotics, synbiotics does not significantly improve the growth of infants and children (Weight, height, BMI, and Head Circumference); The incidence of minor adverse events (OR 0.88, 95% CI 0.70-1.11 P = 0.28) and serious adverse events (OR 0.92, 95% CI 0.62-1.36 P = 0.67) was also comparable to the control group; The intestinal microbial diversity of infants consuming probiotcs, prebiotics, synbiotics supplemented formula was lower than that of infants consuming formula without probiotcs, prebiotics, synbiotics (SMD -0.88, 95% CI -1.66- -0.1 P = 0.03), but the abundance of individual beneficial flora was increased. (SMD 1.62, 95%CI 0.61-2.62 P = 0.002). In particular, the abundance of Lactobacillus (SMD 1.62, 95% CI 0.61-2.62 P = 0.002). For metabolites, synbiotics increased fecal antibody concentrations (SMD 0.47, 95% CI 0.08-0.86 P = 0.02), but fecal short-chain fatty acid concentrations remained balanced in both groups (SMD 0.05 95% CI -0.17-0.28 P = 0.64). Compared to the control group, infants who consumed formula with prebiotics had softer stools (SMD -1.47, 95% CI -2.23 to -0.7 P = 0.002) and lower stool pH (SMD -0.82, 95% CI -1.15- -0.5 P < 0.00001), there is also more frequency of bowel movements (SMD 0.27, 95% CI 0.09-0.44 P = 0.002). CONCLUSIONS Probiotcs, prebiotics, synbiotics supplemented formulas significantly increased abundance of individual probiotics, alter intestinal antibody secretion, and improve bowel movements. Incidence of adverse reactions did not differ between the two groups. So we can choose formula-supplemented probiotcs, prebiotics, synbiotics to maintain the intestinal health of infants.
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Affiliation(s)
- Jiafen Qian
- Department of Pharmacy, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Zongwei Fang
- Department of Pharmacy, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Sijie Chang
- Department of Pharmacy, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Zhiwei Zeng
- Department of Pharmacy, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China
| | - Jinhua Zhang
- Department of Pharmacy, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China.
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Heppner N, Reitmeier S, Heddes M, Merino MV, Schwartz L, Dietrich A, List M, Gigl M, Meng C, van der Veen DR, Schirmer M, Kleigrewe K, Omer H, Kiessling S, Haller D. Diurnal rhythmicity of infant fecal microbiota and metabolites: A randomized controlled interventional trial with infant formula. Cell Host Microbe 2024; 32:573-587.e5. [PMID: 38569545 DOI: 10.1016/j.chom.2024.02.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Revised: 01/13/2024] [Accepted: 02/26/2024] [Indexed: 04/05/2024]
Abstract
Microbiota assembly in the infant gut is influenced by diet. Breastfeeding and human breastmilk oligosaccharides promote the colonization of beneficial bifidobacteria. Infant formulas are supplemented with bifidobacteria or complex oligosaccharides, notably galacto-oligosaccharides (GOS), to mimic breast milk. To compare microbiota development across feeding modes, this randomized controlled intervention study (German Clinical Trial DRKS00012313) longitudinally sampled infant stool during the first year of life, revealing similar fecal bacterial communities between formula- and breast-fed infants (N = 210) but differences across age. Infant formula containing GOS sustained high levels of bifidobacteria compared with formula containing B. longum and B. breve or placebo. Metabolite and bacterial profiling revealed 24-h oscillations and circadian networks. Rhythmicity in bacterial diversity, specific taxa, and functional pathways increased with age and was strongest following breastfeeding and GOS supplementation. Circadian rhythms in dominant taxa were further maintained ex vivo in a chemostat model. Hence, microbiota rhythmicity develops early in life and is impacted by diet.
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Affiliation(s)
- Nina Heppner
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany; ZIEL - Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany
| | - Sandra Reitmeier
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany; ZIEL - Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany
| | - Marjolein Heddes
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany; ZIEL - Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany
| | - Michael Vig Merino
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany; ZIEL - Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany
| | - Leon Schwartz
- Data Science in Systems Biology, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany
| | - Alexander Dietrich
- Data Science in Systems Biology, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany
| | - Markus List
- Data Science in Systems Biology, School of Life Sciences, Technical University of Munich, 85354 Freising, Germany
| | - Michael Gigl
- Bavarian Center for Biomolecular Mass Spectrometry, Technical University of Munich, Gregor-Mendel-Strasse 4, 85354 Freising, Germany
| | - Chen Meng
- Bavarian Center for Biomolecular Mass Spectrometry, Technical University of Munich, Gregor-Mendel-Strasse 4, 85354 Freising, Germany
| | - Daan R van der Veen
- Faculty of Health and Biomedical Science, University of Surrey, 388 Stag Hill Campus, Guildford 17 GU27XH, UK
| | - Melanie Schirmer
- ZIEL - Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany
| | - Karin Kleigrewe
- Bavarian Center for Biomolecular Mass Spectrometry, Technical University of Munich, Gregor-Mendel-Strasse 4, 85354 Freising, Germany
| | - Hélène Omer
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany; ZIEL - Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany
| | - Silke Kiessling
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany; ZIEL - Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany; Faculty of Health and Biomedical Science, University of Surrey, 388 Stag Hill Campus, Guildford 17 GU27XH, UK
| | - Dirk Haller
- Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Strasse 2, 85354 Freising, Germany; ZIEL - Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany.
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Park J, Wickramasinghe S, Mills DA, Lönnerdal BL, Ji P. Iron Fortification and Inulin Supplementation in Early Infancy: Evaluating the Impact on Iron Metabolism and Trace Mineral Status in a Piglet Model. Curr Dev Nutr 2024; 8:102147. [PMID: 38645881 PMCID: PMC11026733 DOI: 10.1016/j.cdnut.2024.102147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 03/18/2024] [Accepted: 03/22/2024] [Indexed: 04/23/2024] Open
Abstract
Background Infant formula in the United States contains abundant iron, raising health concerns about excess iron intake in early infancy. Objectives Using a piglet model, we explored the impact of high iron fortification and prebiotic or synbiotic supplementation on iron homeostasis and trace mineral bioavailability. Methods Twenty-four piglets were stratified and randomly assigned to treatments on postnatal day 2. Piglets were individually housed and received an iron-adequate milk diet (AI), a high-iron milk diet (HI), HI supplemented with 5% inulin (HI with a prebiotic [HIP]), or HIP with an oral gavage of Ligilactobacillus agilis YZ050, an inulin-fermenting strain, every third day (HI with synbiotic [HIS]). Milk was provided in 14 meals daily, mimicking formula feeding in infants. Fecal consistency score and body weight were recorded daily or every other day. Blood and feces were sampled weekly, and tissues collected on postnatal day 29. Data were analyzed using mixed model analysis of variance with repeated measures whenever necessary. Results Diet did not affect growth. HI increased hemoglobin, hematocrit, and serum iron compared to AI. Despite marginal adequacy, AI upregulated iron transporter genes and maintained satisfactory iron status in most pigs. HI upregulated hepcidin gene expression in liver, caused pronounced tissue iron deposition, and markedly increased colonic and fecal iron. Inulin supplementation, regardless of L. agilis YZ050, not only attenuated hepatic iron overload but also decreased colonic and fecal iron without altering pH or the expression of iron regulatory genes. HI lowered zinc (Zn) and copper (Cu) in the duodenum and liver compared to AI, whereas HIP and HIS further decreased Zn and Cu in the liver and diminished colonic and fecal trace minerals. Conclusions Early-infancy excessive iron fortification causes iron overload and compromises Zn and Cu absorption. Inulin decreases trace mineral absorption likely by enhancing gut peristalsis and stool frequency.
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Affiliation(s)
- Jungjae Park
- Department of Nutrition, University of California Davis, CA, United States
| | - Saumya Wickramasinghe
- Department of Food Science and Technology, University of California Davis, CA, United States
| | - David A. Mills
- Department of Food Science and Technology, University of California Davis, CA, United States
| | - Bo L. Lönnerdal
- Department of Nutrition, University of California Davis, CA, United States
| | - Peng Ji
- Department of Nutrition, University of California Davis, CA, United States
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Nagy DU, Sándor-Bajusz KA, Bódy B, Decsi T, Van Harsselaar J, Theis S, Lohner S. Effect of chicory-derived inulin-type fructans on abundance of Bifidobacterium and on bowel function: a systematic review with meta-analyses. Crit Rev Food Sci Nutr 2023; 63:12018-12035. [PMID: 35833477 DOI: 10.1080/10408398.2022.2098246] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
Inulin-type fructans are considered to stimulate the growth of beneficial microorganisms, like Bifidobacterium in the gut and support health. However, both the fructan source and chemical structure may modify these effects. A systematic review was conducted to assess the effects of chicory-derived inulin-type fructans consumed either in specific foods or as dietary supplements on abundance of Bifidobacterium in the gut and on health-related outcomes. Three electronic databases and two clinical trial registries were systematically searched until January 2021. Two authors independently selected randomized controlled trials that investigated with a protocol of minimum seven days supplementation the effect of chicory-derived inulin-type fructans on Bifidobacterium abundance in any population. Meta-analyses with random-effects model were conducted on Bifidobacterium abundance and bowel function parameters. We evaluated risk of bias using Cochrane RoB tool. Chicory-derived inulin-type fructans at a dose of 3-20 g/day significantly increased Bifidobacterium abundance in participants with an age range from 0 to 83 years (standardized mean difference: 0.83, 95% CI: 0.58-1.08; p < 0.01; 50 studies; 2525 participants). Significant bifidogenic effects were observed in healthy individuals and in populations with health impairments, except gastrointestinal disorders. Significant beneficial effects on bowel function parameters were observed in healthy subjects. Chicory-derived inulin-type fructans may have significant bifidogenic effects and may beneficially influence bowel function in healthy individuals. PROSPERO registration number CRD42020162892.
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Affiliation(s)
- Dávid U Nagy
- Department of Paediatrics, Clinical Center of the University of Pécs, Medical School, University of Pécs, Pécs, Hungary
- Institute of Geobotany/Plant Ecology, Martin-Luther-University, Halle (Saale), Germany
| | - Kinga Amália Sándor-Bajusz
- Department of Paediatrics, Clinical Center of the University of Pécs, Medical School, University of Pécs, Pécs, Hungary
| | - Blanka Bódy
- Department of Paediatrics, Clinical Center of the University of Pécs, Medical School, University of Pécs, Pécs, Hungary
| | - Tamás Decsi
- Department of Paediatrics, Clinical Center of the University of Pécs, Medical School, University of Pécs, Pécs, Hungary
| | | | - Stephan Theis
- BENEO-Institute, c/o BENEO GmbH, Obrigheim, (Germany)
| | - Szimonetta Lohner
- Department of Public Health Medicine, Medical School, University of Pécs, Pécs, Hungary
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Baaleman DF, Wegh CAM, de Leeuw TJM, van Etten-Jamaludin FS, Vaughan EE, Schoterman MHC, Belzer C, Smidt H, Tabbers MM, Benninga MA, Koppen IJN. What are Normal Defecation Patterns in Healthy Children up to Four Years of Age? A Systematic Review and Meta-Analysis. J Pediatr 2023; 261:113559. [PMID: 37331467 DOI: 10.1016/j.jpeds.2023.113559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 06/08/2023] [Accepted: 06/12/2023] [Indexed: 06/20/2023]
Abstract
OBJECTIVE To summarize available data on defecation frequency and stool consistency of healthy children up to age 4 in order to estimate normal references values. STUDY DESIGN Systematic review including cross-sectional, observational, and interventional studies published in English, that reported on defecation frequency and/or stool consistency in healthy children 0-4 years old. RESULTS Seventy-five studies were included with 16 393 children and 40 033 measurements of defecation frequency and/or stool consistency. Based on visual inspection of defecation frequency data, a differentiation was made between two age categories: young infants (0-14 weeks old) and young children (15 weeks-4 years old). Young infants had a mean defecation frequency of 21.8 per week (95 % CI, 3.9-35.2) compared with 10.9 (CI, 5.7-16.7) in young children (P < .001). Among young infants, human milk-fed (HMF) infants had the highest mean defecation frequency per week (23.2 [CI, 8.8-38.1]), followed by formula-fed (FF) infants (13.7 [CI 5.4-23.9]), and mixed-fed (MF) infants (20.7 [CI, 7.0-30.2]). Hard stools were infrequently reported in young infants (1.5%) compared with young children (10.5%), and a reduction in the frequency of soft/watery stools was observed with higher age (27.0% in young infants compared with 6.2% in young children). HMF young infants had softer stools compared with FF young infants. CONCLUSIONS Young infants (0-14 weeks old) have softer and more frequent stools compared with young children (15 weeks-4 years old).
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Affiliation(s)
- Desiree F Baaleman
- Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
| | - Carrie A M Wegh
- Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands; Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
| | - Tessa J M de Leeuw
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
| | | | | | | | - Clara Belzer
- Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Hauke Smidt
- Laboratory of Microbiology, Wageningen University & Research, Wageningen, The Netherlands
| | - Merit M Tabbers
- Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Marc A Benninga
- Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Ilan J N Koppen
- Department of Pediatric Gastroenterology and Nutrition, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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Zhang S, Lv S, Li Y, Wei D, Zhou X, Niu X, Yang Z, Song W, Zhang Z, Peng D. Prebiotics modulate the microbiota-gut-brain axis and ameliorate cognitive impairment in APP/PS1 mice. Eur J Nutr 2023; 62:2991-3007. [PMID: 37460822 DOI: 10.1007/s00394-023-03208-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 07/10/2023] [Indexed: 08/31/2023]
Abstract
PURPOSE Prebiotics, including fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), stimulate beneficial gut bacteria and may be helpful for patients with Alzheimer's disease (AD). This study aimed to compare the effects of FOS and GOS, alone or in combination, on AD mice and to identify their underlying mechanisms. METHODS Six-month-old APP/PS1 mice and wild-type mice were orally administered FOS, GOS, FOS + GOS or water by gavage for 6 weeks and then subjected to relative assays, including behavioral tests, biochemical assays and 16S rRNA sequencing. RESULTS Through behavioral tests, we found that GOS had the best effect on reversing cognitive impairment in APP/PS1 mice, followed by FOS + GOS, while FOS had no effect. Through biochemical techniques, we found that GOS and FOS + GOS had effects on multiple targets, including diminishing Aβ burden and proinflammatory IL-1β and IL-6 levels, and changing the concentrations of neurotransmitters GABA and 5-HT in the brain. In contrast, FOS had only a slight anti-inflammatory effect. Moreover, through 16S rRNA sequencing, we found that prebiotics changed composition of gut microbiota. Notably, GOS increased relative abundance of Lactobacillus, FOS increased that of Bifidobacterium, and FOS + GOS increased that of both. Furthermore, prebiotics downregulated the expression levels of proteins of the TLR4-Myd88-NF-κB pathway in the colons and cortexes, suggesting the involvement of gut-brain mechanism in alleviating neuroinflammation. CONCLUSION Among the three prebiotics, GOS was the optimal one to alleviate cognitive impairment in APP/PS1 mice and the mechanism was attributed to its multi-target role in alleviating Aβ pathology and neuroinflammation, changing neurotransmitter concentrations, and modulating gut microbiota.
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Affiliation(s)
- Shujuan Zhang
- Department of Rehabilitation Medicine, Xuan Wu Hospital, Capital Medical University, 45 Chang Chun Street, Beijing, 100053, China
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China
- Department of Neurology, China-Japan Friendship Hospital, 2 Yinghuayuan East Street, Chaoyang District, Beijing, 100029, China
| | - Shuang Lv
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China
- Department of Neurology, China-Japan Friendship Hospital, 2 Yinghuayuan East Street, Chaoyang District, Beijing, 100029, China
- Department of Rheumatology, the First Hospital of Hebei Medical University, No. 89 Donggang Road, Yuhua District, Shijiazhuang, 050031, Hebei, China
| | - Yiming Li
- Department of Cardiovasology, the First Hospital of Hebei Medical University, No. 89 Donggang Road, Yuhua District, Shijiazhuang, 050031, Hebei, China
| | - Dongfeng Wei
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Xiao Zhou
- Department of Neurology, Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100005, China
| | - Xiaoqian Niu
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China
- Department of Neurology, China-Japan Friendship Hospital, 2 Yinghuayuan East Street, Chaoyang District, Beijing, 100029, China
| | - Ziyuan Yang
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China
- Department of Neurology, China-Japan Friendship Hospital, 2 Yinghuayuan East Street, Chaoyang District, Beijing, 100029, China
| | - Weiqun Song
- Department of Rehabilitation Medicine, Xuan Wu Hospital, Capital Medical University, 45 Chang Chun Street, Beijing, 100053, China.
| | - Zhanjun Zhang
- State Key Laboratory of Cognitive Neuroscience and Learning and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, 100875, China.
| | - Dantao Peng
- Peking University China-Japan Friendship School of Clinical Medicine, Beijing, 100029, China.
- Department of Neurology, China-Japan Friendship Hospital, 2 Yinghuayuan East Street, Chaoyang District, Beijing, 100029, China.
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10
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Pantazi AC, Balasa AL, Mihai CM, Chisnoiu T, Lupu VV, Kassim MAK, Mihai L, Frecus CE, Chirila SI, Lupu A, Andrusca A, Ionescu C, Cuzic V, Cambrea SC. Development of Gut Microbiota in the First 1000 Days after Birth and Potential Interventions. Nutrients 2023; 15:3647. [PMID: 37630837 PMCID: PMC10457741 DOI: 10.3390/nu15163647] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Revised: 08/13/2023] [Accepted: 08/17/2023] [Indexed: 08/27/2023] Open
Abstract
The first 1000 days after birth represent a critical window for gut microbiome development, which is essential for immune system maturation and overall health. The gut microbiome undergoes major changes during this period due to shifts in diet and environment. Disruptions to the microbiota early in life can have lasting health effects, including increased risks of inflammatory disorders, autoimmune diseases, neurological disorders, and obesity. Maternal and environmental factors during pregnancy and infancy shape the infant gut microbiota. In this article, we will review how maintaining a healthy gut microbiome in pregnancy and infancy is important for long-term infant health. Furthermore, we briefly include fungal colonization and its effects on the host immune function, which are discussed as part of gut microbiome ecosystem. Additionally, we will describe how potential approaches such as hydrogels enriched with prebiotics and probiotics, gut microbiota transplantation (GMT) during pregnancy, age-specific microbial ecosystem therapeutics, and CRISPR therapies targeting the gut microbiota hold potential for advancing research and development. Nevertheless, thorough evaluation of their safety, effectiveness, and lasting impacts is crucial prior to their application in clinical approach. The article emphasizes the need for continued research to optimize gut microbiota and immune system development through targeted early-life interventions.
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Affiliation(s)
- Alexandru Cosmin Pantazi
- Pediatrics Department, Faculty of Medicine, “Ovidius” University, 900470 Constanta, Romania (A.L.B.)
- Pediatrics Department, County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Adriana Luminita Balasa
- Pediatrics Department, Faculty of Medicine, “Ovidius” University, 900470 Constanta, Romania (A.L.B.)
- Pediatrics Department, County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Cristina Maria Mihai
- Pediatrics Department, Faculty of Medicine, “Ovidius” University, 900470 Constanta, Romania (A.L.B.)
- Pediatrics Department, County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Tatiana Chisnoiu
- Pediatrics Department, Faculty of Medicine, “Ovidius” University, 900470 Constanta, Romania (A.L.B.)
- Pediatrics Department, County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Vasile Valeriu Lupu
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | | | - Larisia Mihai
- Pediatrics Department, Faculty of Medicine, “Ovidius” University, 900470 Constanta, Romania (A.L.B.)
- Pediatrics Department, County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Corina Elena Frecus
- Pediatrics Department, Faculty of Medicine, “Ovidius” University, 900470 Constanta, Romania (A.L.B.)
- Pediatrics Department, County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | | | - Ancuta Lupu
- Pediatrics Department, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania
| | - Antonio Andrusca
- Pediatrics Department, Faculty of Medicine, “Ovidius” University, 900470 Constanta, Romania (A.L.B.)
- Pediatrics Department, County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Constantin Ionescu
- Faculty of Medicine, “Ovidius” University, 900470 Constanta, Romania (S.I.C.)
| | - Viviana Cuzic
- Pediatrics Department, Faculty of Medicine, “Ovidius” University, 900470 Constanta, Romania (A.L.B.)
- Pediatrics Department, County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Simona Claudia Cambrea
- Infectious Diseases Department, Faculty of Medicine, “Ovidius” University, 900470 Constanta, Romania
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Sharif S, Oddie SJ, Heath PT, McGuire W. Prebiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Cochrane Database Syst Rev 2023; 6:CD015133. [PMID: 37262358 PMCID: PMC10234253 DOI: 10.1002/14651858.cd015133.pub2] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
BACKGROUND Dietary supplementation with prebiotic oligosaccharides to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of necrotising enterocolitis (NEC) and associated mortality and morbidity in very preterm or very low birth weight (VLBW) infants. OBJECTIVES To assess the benefits and harms of enteral supplementation with prebiotics (versus placebo or no treatment) for preventing NEC and associated morbidity and mortality in very preterm or VLBW infants. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Maternity and Infant Care database and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), from the earliest records to July 2022. We searched clinical trials databases and conference proceedings, and examined the reference lists of retrieved articles. SELECTION CRITERIA We included randomised controlled trials (RCTs) and quasi-RCTs comparing prebiotics with placebo or no prebiotics in very preterm (< 32 weeks' gestation) or VLBW (< 1500 g) infants. The primary outcomes were NEC and all-cause mortality, and the secondary outcomes were late-onset invasive infection, duration of hospitalisation since birth, and neurodevelopmental impairment. DATA COLLECTION AND ANALYSIS Two review authors separately evaluated risk of bias of the trials, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference (MD), with associated 95% confidence intervals (CIs). The primary outcomes of interest were NEC and all-cause mortality; our secondary outcome measures were late-onset (> 48 hours after birth) invasive infection, duration of hospitalisation, and neurodevelopmental impairment. We used the GRADE approach to assess the level of certainty of the evidence. MAIN RESULTS We included seven trials in which a total of 705 infants participated. All the trials were small (mean sample size 100). Lack of clarity on methods to conceal allocation and mask caregivers or investigators were potential sources of bias in three of the trials. The studied prebiotics were fructo- and galacto-oligosaccharides, inulin, and lactulose, typically administered daily with enteral feeds during birth hospitalisation. Meta-analyses of data from seven trials (686 infants) suggest that prebiotics may result in little or no difference in NEC (RR 0.97, 95% CI 0.60 to 1.56; RD none fewer per 1000, 95% CI 50 fewer to 40 more; low-certainty evidence), all-cause mortality (RR 0.43, 95% CI 0.20 to 0.92; 40 per 1000 fewer, 95% CI 70 fewer to none fewer; low-certainty evidence), or late-onset invasive infection (RR 0.79, 95% CI 0.60 to 1.06; 50 per 1000 fewer, 95% CI 100 fewer to 10 more; low-certainty evidence) prior to hospital discharge. The certainty of this evidence is low because of concerns about the risk of bias in some trials and the imprecision of the effect size estimates. The data available from one trial provided only very low-certainty evidence about the effect of prebiotics on measures of neurodevelopmental impairment (Bayley Scales of Infant Development (BSID) Mental Development Index score < 85: RR 0.84, 95% CI 0.25 to 2.90; very low-certainty evidence; BSID Psychomotor Development Index score < 85: RR 0.24, 95% 0.03 to 2.00; very low-certainty evidence; cerebral palsy: RR 0.35, 95% CI 0.01 to 8.35; very low-certainty evidence). AUTHORS' CONCLUSIONS The available trial data provide low-certainty evidence about the effects of prebiotics on the risk of NEC, all-cause mortality before discharge, and invasive infection, and very low-certainty evidence about the effect on neurodevelopmental impairment for very preterm or VLBW infants. Our confidence in the effect estimates is limited; the true effects may be substantially different. Large, high-quality trials are needed to provide evidence of sufficient validity to inform policy and practice decisions.
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Key Words
- humans
- infant, newborn
- enterocolitis, necrotizing
- enterocolitis, necrotizing/etiology
- enterocolitis, necrotizing/prevention & control
- infant, extremely premature
- infant, premature, diseases
- infant, premature, diseases/etiology
- infant, premature, diseases/prevention & control
- infant, very low birth weight
- infections
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Affiliation(s)
- Sahar Sharif
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Sam J Oddie
- Bradford Neonatology, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
| | - Paul T Heath
- Division of Child Health and Vaccine Institute, St. George's, University of London, London, UK
| | - William McGuire
- Centre for Reviews and Dissemination, University of York, York, UK
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12
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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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13
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Study Protocol for a Randomised Controlled Trial Investigating the Effects of Maternal Prebiotic Fibre Dietary Supplementation from Mid-Pregnancy to Six Months’ Post-Partum on Child Allergic Disease Outcomes. Nutrients 2022; 14:nu14132753. [PMID: 35807933 PMCID: PMC9268759 DOI: 10.3390/nu14132753] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 06/28/2022] [Accepted: 06/30/2022] [Indexed: 02/01/2023] Open
Abstract
Infant allergy is the most common early manifestation of an increasing propensity for inflammation and immune dysregulation in modern environments. Refined low-fibre diets are a major risk for inflammatory diseases through adverse effects on the composition and function of gut microbiota. This has focused attention on the potential of prebiotic dietary fibres to favourably change gut microbiota, for local and systemic anti-inflammatory effects. In pregnancy, the immunomodulatory effects of prebiotics may also have benefits for the developing fetal immune system, and provide a potential dietary strategy to reduce the risk of allergic disease. Here, we present the study protocol for a double-blinded, randomised controlled trial investigating the effects of maternal prebiotics supplementation on child allergic disease outcomes. Eligible pregnant women have infants with a first-degree relative with a history of medically diagnosed allergic disease. Consented women are randomised to consume either prebiotics (galacto-oligosaccharides and fructo-oligosaccharides) or placebo (maltodextrin) powder daily from 18–20 weeks’ gestation to six months’ post-partum. The target sample size is 652 women. The primary outcome is infant medically diagnosed eczema; secondary outcomes include allergen sensitisation, food allergies and recurrent wheeze. Breast milk, stool and blood samples are collected at multiple timepoints for further analysis.
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14
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Otiti MI, Kariuki S, Wang D, Hall LJ, Ter Kuile FO, Allen S. PRObiotics and SYNbiotics to improve gut health and growth in infants in western Kenya (PROSYNK Trial): study protocol for a 4-arm, open-label, randomised, controlled trial. Trials 2022; 23:284. [PMID: 35410317 PMCID: PMC8996226 DOI: 10.1186/s13063-022-06211-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Accepted: 03/26/2022] [Indexed: 11/10/2022] Open
Abstract
Background Malnutrition amongst under-fives remains common in resource-poor countries and is resistant to current interventions. New opportunities have emerged to target “environmental enteric dysfunction” (EED) that refers to the abnormal gut structure and function that results from colonisation of the gut with pathogenic microbes and compromises nutrition and growth in early life. Although the gut microbiome may provide a defence against ingested gut pathogens through colonisation resistance, its development is adversely affected by multiple environmental factors. Dietary supplements of pro- or synbiotics may build the resilience of the gut microbiome against these environmental factors and boost colonisation resistance. We aim to assess whether dietary supplementation of newborns in rural Kenya with pro/synbiotics prevents or ameliorates EED and improves growth. Methods Six hundred newborns less than 4 days old will be recruited from Homa Bay County Teaching and Referral Hospital, western Kenya. Newborns will be randomly allocated, stratified by HIV exposure, in a 1:1:1:1 ratio to one of 4 study arms to receive either of two synbiotics, a probiotic or no supplement. Supplements will be given daily for 10 days and then weekly until 6 months of age. Participants will be followed until the age of 2 years. The primary outcome is systemic inflammation at 6 months assessed by plasma alpha-1-acid glycoprotein. Secondary outcomes include biomarkers of gut health and growth, anthropometric indices, morbidity and mortality. Discussion As dietary supplements with pro- or synbiotics may improve gut health and can be administered in early life, our findings may inform the package of interventions to prevent malnutrition and improve growth in Africa and similar low-resource settings. Trial registration Pan African Clinical Trials Registry, Trial number: PACTR202003893276712. Date: 02/03/2020 https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9798 Supplementary Information The online version contains supplementary material available at 10.1186/s13063-022-06211-1.
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15
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Sharif S, Heath PT, Oddie SJ, McGuire W. Synbiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Cochrane Database Syst Rev 2022; 3:CD014067. [PMID: 35230697 PMCID: PMC8887627 DOI: 10.1002/14651858.cd014067.pub2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
BACKGROUND Intestinal dysbiosis may contribute to the pathogenesis of necrotising enterocolitis (NEC) in very preterm or very low birth weight (VLBW) infants. Dietary supplementation with synbiotics (probiotic micro-organisms combined with prebiotic oligosaccharides) to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of NEC and associated mortality and morbidity. OBJECTIVES To assess the effect of enteral supplementation with synbiotics (versus placebo or no treatment, or versus probiotics or prebiotics alone) for preventing NEC and associated morbidity and mortality in very preterm or VLBW infants. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, the Maternity and Infant Care database and CINAHL, from earliest records to 17 June 2021. We searched clinical trials databases and conference proceedings, and examined the reference lists of retrieved articles. SELECTION CRITERIA We included randomised controlled trials (RCTs) and quasi-RCTs comparing prophylactic synbiotics supplementation with placebo or no synbiotics in very preterm (< 32 weeks' gestation) or very low birth weight (< 1500 g) infants. DATA COLLECTION AND ANALYSIS Two review authors separately performed the screening and selection process, evaluated risk of bias of the trials, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference, with associated 95% confidence intervals (CIs). We used the GRADE approach to assess the level of certainty for effects on NEC, all-cause mortality, late-onset invasive infection, and neurodevelopmental impairment. MAIN RESULTS We included six trials in which a total of 925 infants participated. Most trials were small (median sample size 200). Lack of clarity on methods used to conceal allocation and mask caregivers or investigators were potential sources of bias in four of the trials. The studied synbiotics preparations contained lactobacilli or bifidobacteria (or both) combined with fructo- or galacto-oligosaccharides (or both). Meta-analyses suggested that synbiotics may reduce the risk of NEC (RR 0.18, 95% CI 0.09 to 0.40; RD 70 fewer per 1000, 95% CI 100 fewer to 40 fewer; number needed to treat for an additional beneficial outcome (NNTB) 14, 95% CI 10 to 25; six trials (907 infants); low certainty evidence); and all-cause mortality prior to hospital discharge (RR 0.53, 95% CI 0.33 to 0.85; RD 50 fewer per 1000, 95% CI 120 fewer to 100 fewer; NNTB 20, 95% CI 8 to 100; six trials (925 infants); low-certainty evidence). Synbiotics may have little or no effect on late-onset invasive infection, but the evidence is very uncertain (RR 0.84, 95% CI 0.58 to 1.21; RD 20 fewer per 1000, 95% CI 70 fewer to 30 more; five trials (707 infants); very low-certainty evidence). None of the trials assessed neurodevelopmental outcomes. In the absence of high levels of heterogeneity, we did not undertake any subgroup analysis (including the type of feeding). AUTHORS' CONCLUSIONS The available trial data provide only low-certainty evidence about the effects of synbiotics on the risk of NEC and associated morbidity and mortality for very preterm or very low birth weight infants. Our confidence in the effect estimates is limited; the true effects may be substantially different from these estimates. Large, high-quality trials would be needed to provide evidence of sufficient validity and applicability to inform policy and practice.
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Affiliation(s)
- Sahar Sharif
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Paul T Heath
- Division of Child Health and Vaccine Institute, St. George's, University of London, London, UK
| | - Sam J Oddie
- Bradford Neonatology, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
| | - William McGuire
- Centre for Reviews and Dissemination, University of York, York, UK
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Ferro LE, Crowley LN, Bittinger K, Friedman ES, Decker JE, Russel K, Katz S, Kim JK, Trabulsi J. Effects of prebiotics, probiotics, and synbiotics on the infant gut microbiota and other health outcomes: A systematic review. Crit Rev Food Sci Nutr 2022; 63:5620-5642. [PMID: 37667870 PMCID: PMC10480560 DOI: 10.1080/10408398.2021.2022595] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
The primary aim of this review was to systematically evaluate the literature regarding the effect of pre-, pro-, or synbiotic supplementation in infant formula on the gastrointestinal microbiota. The Cochrane methodology for systematic reviews of randomized controlled trials (RCTs) was employed. Five databases were searched and 32 RCTs (2010-2021) were identified for inclusion: 20 prebiotic, 6 probiotic, and 6 synbiotic. The methods utilized to evaluate gastrointestinal microbiota varied across studies and included colony plating, fluorescence in situ hybridization, quantitative real-time polymerase chain reaction, or tagged sequencing of the 16S rRNA gene. Fecal Bifidobacterium levels increased with supplementation of prebiotics and synbiotics but not with probiotics alone. Probiotic and synbiotic supplementation generally increased fecal levels of the bacterial strain supplemented in the formula. Across all pre-, pro-, and synbiotic-supplemented formulas, results were inconsistent regarding fecal Clostridium levels. Fecal pH was lower with some prebiotic and synbiotic supplementation; however, no difference was seen with probiotics. Softer stools were often reported in infants supplemented with pre- and synbiotics, yet results were inconsistent for probiotic-supplemented formula. Limited evidence demonstrates that pre- and synbiotic supplementation increases fecal Bifidobacterium levels. Future studies utilizing comprehensive methodologies and additional studies in probiotics and synbiotics are warranted.
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Affiliation(s)
- Lynn E. Ferro
- Department of Behavioral Health and Nutrition, University of Delaware, STAR Tower, 100 Discovery Blvd., Newark, DE 19713, USA
| | - Liana N. Crowley
- Department of Behavioral Health and Nutrition, University of Delaware, STAR Tower, 100 Discovery Blvd., Newark, DE 19713, USA
| | - Kyle Bittinger
- Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
| | - Elliot S. Friedman
- Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Jessica E. Decker
- Department of Behavioral Health and Nutrition, University of Delaware, STAR Tower, 100 Discovery Blvd., Newark, DE 19713, USA
| | - Kathryn Russel
- Metropolitan Area Neighborhood Nutrition Alliance, 420 N 20 Street, Philadelphia, PA 19130, USA
| | - Sarah Katz
- Reference and Instructional Services Department, University of Delaware, 181 S. College Avenue, Newark, DE 19717, USA
| | - Jae Kyeom Kim
- Department of Behavioral Health and Nutrition, University of Delaware, STAR Tower, 100 Discovery Blvd., Newark, DE 19713, USA
| | - Jillian Trabulsi
- Department of Behavioral Health and Nutrition, University of Delaware, STAR Tower, 100 Discovery Blvd., Newark, DE 19713, USA
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17
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Pyle S. Human Gut Microbiota and the Influence of Probiotics, Prebiotics, and Micronutrients. COMPREHENSIVE GUT MICROBIOTA 2022:271-288. [DOI: 10.1016/b978-0-12-819265-8.00076-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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18
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Shi S, Liu J, Dong J, Hu J, Liu Y, Feng J, Zhou D. Research progress on the regulation mechanism of probiotics on the microecological flora of infected intestines in livestock and poultry. Lett Appl Microbiol 2021; 74:647-655. [PMID: 34882816 DOI: 10.1111/lam.13629] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 12/05/2021] [Accepted: 12/06/2021] [Indexed: 12/12/2022]
Abstract
The animal intestine is a complex ecosystem composed of host cells, gut microbiota and available nutrients. Gut microbiota can prevent the occurrence of intestinal diseases in animals by regulating the homeostasis of the intestinal environment. The intestinal microbiota is a complex and stable microbial community, and the homeostasis of the intestinal environment is closely related to the invasion of intestinal pathogens, which plays an important role in protecting the host from pathogen infections. Probiotics are strains of microorganisms that are beneficial to health, and their potential has recently led to a significant increase in studies on the regulation of intestinal flora. Various potential mechanisms of action have been proposed on probiotics, especially mediating the regulation mechanism of the intestinal flora on the host, mainly including competitive inhibition of pathogens, stimulation of the host's adaptive immune system and regulation of the intestinal flora. The advent of high-throughput sequencing technology has given us a clearer understanding and has facilitated the development of research methods to investigate the intestinal microecological flora. This review will focus on the regulation of probiotics on the microbial flora of intestinal infections in livestock and poultry and will depict future research directions.
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Affiliation(s)
- S Shi
- College of Life Sciences, Anqing Normal University and Anhui Key Laboratory of Biodiversity Research and Ecological Protection in Southwest Anhui Province, Anqing, P. R. China
| | | | - J Dong
- College of Life Sciences, Anqing Normal University and Anhui Key Laboratory of Biodiversity Research and Ecological Protection in Southwest Anhui Province, Anqing, P. R. China
| | - J Hu
- College of Life Sciences, Anqing Normal University and Anhui Key Laboratory of Biodiversity Research and Ecological Protection in Southwest Anhui Province, Anqing, P. R. China
| | - Y Liu
- College of Life Sciences, Anqing Normal University and Anhui Key Laboratory of Biodiversity Research and Ecological Protection in Southwest Anhui Province, Anqing, P. R. China
| | - J Feng
- Susong Chunrun Food Co., Ltd, Anqing, P. R. China
| | - D Zhou
- College of Life Sciences, Anqing Normal University and Anhui Key Laboratory of Biodiversity Research and Ecological Protection in Southwest Anhui Province, Anqing, P. R. China
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Fabiano V, Indrio F, Verduci E, Calcaterra V, Pop TL, Mari A, Zuccotti GV, Cullu Cokugras F, Pettoello-Mantovani M, Goulet O. Term Infant Formulas Influencing Gut Microbiota: An Overview. Nutrients 2021; 13:4200. [PMID: 34959752 PMCID: PMC8708119 DOI: 10.3390/nu13124200] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 11/19/2021] [Accepted: 11/20/2021] [Indexed: 02/05/2023] Open
Abstract
Intestinal colonization of the neonate is highly dependent on the term of pregnancy, the mode of delivery, the type of feeding [breast feeding or formula feeding]. Postnatal immune maturation is dependent on the intestinal microbiome implementation and composition and type of feeding is a key issue in the human gut development, the diversity of microbiome, and the intestinal function. It is well established that exclusive breastfeeding for 6 months or more has several benefits with respect to formula feeding. The composition of the new generation of infant formulas aims in mimicking HM by reproducing its beneficial effects on intestinal microbiome and on the gut associated immune system (GAIS). Several approaches have been developed currently for designing new infant formulas by the addition of bioactive ingredients such as human milk oligosaccharides (HMOs), probiotics, prebiotics [fructo-oligosaccharides (FOSs) and galacto-oligosaccharides (GOSs)], or by obtaining the so-called post-biotics also known as milk fermentation products. The aim of this article is to guide the practitioner in the understanding of these different types of Microbiota Influencing Formulas by listing and summarizing the main concepts and characteristics of these different models of enriched IFs with bioactive ingredients.
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Affiliation(s)
- Valentina Fabiano
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, Università degli Studi di Milano, 20154 Milan, Italy; (V.F.); (E.V.); (V.C.); (A.M.); (G.V.Z.)
| | - Flavia Indrio
- Department of Medical and Surgical Sciences, University of Foggia, 71100 Foggia, Italy
- European Paediatric Association/Union of National European Paediatric Societies and Associations, 10115 Berlin, Germany; (T.L.P.); (F.C.C.); (M.P.-M.)
| | - Elvira Verduci
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, Università degli Studi di Milano, 20154 Milan, Italy; (V.F.); (E.V.); (V.C.); (A.M.); (G.V.Z.)
| | - Valeria Calcaterra
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, Università degli Studi di Milano, 20154 Milan, Italy; (V.F.); (E.V.); (V.C.); (A.M.); (G.V.Z.)
- Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy
| | - Tudor Lucian Pop
- European Paediatric Association/Union of National European Paediatric Societies and Associations, 10115 Berlin, Germany; (T.L.P.); (F.C.C.); (M.P.-M.)
- Second Paediatric Clinic, Department of Mother and Child, University of Medicine and Pharmacy Iuliu Hatieganu, 400177 Cluj-Napoca, Romania
| | - Alessandra Mari
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, Università degli Studi di Milano, 20154 Milan, Italy; (V.F.); (E.V.); (V.C.); (A.M.); (G.V.Z.)
| | - Gian Vincenzo Zuccotti
- Department of Pediatrics, Vittore Buzzi Children’s Hospital, Università degli Studi di Milano, 20154 Milan, Italy; (V.F.); (E.V.); (V.C.); (A.M.); (G.V.Z.)
| | - Fugen Cullu Cokugras
- European Paediatric Association/Union of National European Paediatric Societies and Associations, 10115 Berlin, Germany; (T.L.P.); (F.C.C.); (M.P.-M.)
- Paediatric Gastroenterology, Hepatology and Nutrition, Cerrahpasa Medical Faculty, Istanbul University, Istanbul 34000, Turkey
| | - Massimo Pettoello-Mantovani
- European Paediatric Association/Union of National European Paediatric Societies and Associations, 10115 Berlin, Germany; (T.L.P.); (F.C.C.); (M.P.-M.)
- Department of Pediatrics, Scientific Institute ‘Casa Sollievo della Sofferenza’, University of Foggia, 71122 Foggia, Italy
- Association pour l’Activité et la Recherche Scìentifiques, EPA-UNEPSA/ARS, 2000 Neuchâtel, Switzerland
| | - Olivier Goulet
- Department of Paediatric Gastroenterology, and Nutrition, Intestinal Failure Rehabilitation Centre, National Reference Centre for Rare Digestive Diseases, Necker-Enfants Malades Hospital, Paris Centre University and Paris-Descartes School of Medicine, 75000 Paris, France;
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20
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Vandenplas Y, De Mulder N, De Greef E, Huysentruyt K. Plant-Based Formulas and Liquid Feedings for Infants and Toddlers. Nutrients 2021; 13:4026. [PMID: 34836284 PMCID: PMC8618919 DOI: 10.3390/nu13114026] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 11/01/2021] [Accepted: 11/09/2021] [Indexed: 12/26/2022] Open
Abstract
Exclusive breastfeeding is the recommended feeding for all infants. Recent research has focused on the importance of balanced feeding during the first 1000 days, starting at conception with a balanced diet of the pregnant woman, up to the age of two years. The following step, a balanced diet after the age of two years is a challenge, as the dietary intake becomes more diversified. The role of young-child formula in this process is debated. This paper discusses the use of planted-based drinks, since they are a valuable and progressively more popular alternative for cow's milk, if nutritionally adapted to the requirements of toddlers. Plant-based drinks are per definition lactose free.
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Affiliation(s)
- Yvan Vandenplas
- Pediatric Gastroenterology, KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, 1090 Brussels, Belgium; (N.D.M.); (E.D.G.); (K.H.)
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21
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Josyabhatla R, Imseis EM. Pediatric intestinal failure and the microbiome. Semin Perinatol 2021; 45:151453. [PMID: 34332780 DOI: 10.1016/j.semperi.2021.151453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Neonatal intestinal failure is a complex medical condition that is associated with the need for long term parenteral nutrition and its associated complications. The microbiome in this diseased state is different from what is now understood to be a healthy microbiome. The effect of this dysbiotic microbiome on the complications of intestinal failure are only starting to be understood. The ability to modulate the microbiome with enteral/parenteral nutrients, as well probiotics to a healthier state, is an exciting opportunity that holds promise.
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Affiliation(s)
- Rohit Josyabhatla
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, University of Texas Health Science Center at Houston, TX, USA
| | - Essam M Imseis
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, University of Texas Health Science Center at Houston, TX, USA.
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22
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Tonon KM, Tomé TM, Mosquera EMB, Perina NP, Lazarini T. The Effect of Infant Formulas With 4 or 8 g/L GOS/FOS on Growth, Gastrointestinal Symptoms, and Behavioral Patterns: A Prospective Cohort Study. Glob Pediatr Health 2021; 8:2333794X211044115. [PMID: 34527766 PMCID: PMC8436285 DOI: 10.1177/2333794x211044115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 08/16/2021] [Indexed: 11/15/2022] Open
Abstract
There is a lack of studies investigating the clinical benefits of prebiotic-supplemented infant formula. In this study, healthy infants that started, on medical recommendation, artificial feeding with one of 2 infant formulas containing 4 g/L of GOS/FOS (9:1) (IF4 group; n = 60) or 8 g/L of GOS/FOS (9:1) (IF8 group; n = 60) were followed for 30 days to the evaluation of growth and gastrointestinal symptoms. Exclusively breastfed infants (EBF; n = 60) were followed up as a reference. Both infant formulas supported adequate weight gain, however, IF4 formula promotes growth more similar to breastfed infants. There was no additional benefit of a dose higher than 4 g/L of GOS/FOS on gastrointestinal symptoms.
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23
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Morales-Ferré C, Azagra-Boronat I, Massot-Cladera M, Tims S, Knipping K, Garssen J, Knol J, Franch À, Castell M, Rodríguez-Lagunas MJ, Pérez-Cano FJ. Effects of a Postbiotic and Prebiotic Mixture on Suckling Rats' Microbiota and Immunity. Nutrients 2021; 13:2975. [PMID: 34578853 PMCID: PMC8469903 DOI: 10.3390/nu13092975] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/23/2021] [Accepted: 08/25/2021] [Indexed: 01/04/2023] Open
Abstract
Human milk serves as a model for infant formula providing nutritional solutions for infants not able to receive enough mother's milk. Infant formulas aim to mimic the composition and functionality of human milk by providing ingredients reflecting those of the latest human milk insights, such as prebiotics, probiotics and postbiotics. The aim of this study was to examine the effects of the supplementation with a postbiotic (LactofidusTM) and its combination with the prebiotics short-chain galactooligosaccharides (scGOS) and long-chain fructooligosaccharides (lcFOS) in a preclinical model of healthy suckling rats. Pups were supplemented daily with LactofidusTM (POST group) and/or scGOS/lcFOS (P+P and PRE groups, respectively). Body weight and fecal consistency were analyzed. At the end of the study, immunoglobulin (Ig) profile, intestinal gene expression, microbiota composition and short chain fatty acid (SCFA) proportion were quantified. The supplementation with all nutritional interventions modulated the Ig profile, but the prebiotic mixture and the postbiotic induced differential effects: whereas scGOS/lcFOS induced softer feces and modulated microbiota composition and SCFA profile, Lactofidus™ upregulated Toll-like receptors gene expression. The use of the combination of scGOS/lcFOS and Lactofidus™ showed the effects observed for the oligosaccharides separately, as well as showing a synergistic impact on animal growth. Thus, the combined use of both products seems to be a good strategy to modulate immune and microbial features in early life.
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Affiliation(s)
- Carla Morales-Ferré
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (C.M.-F.); (I.A.-B.); (M.M.-C.); (À.F.); (M.C.); (F.J.P.-C.)
- Nutrition and Food Safety Research Institute (INSA-UB), 08921 Santa Coloma de Gramenet, Spain
| | - Ignasi Azagra-Boronat
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (C.M.-F.); (I.A.-B.); (M.M.-C.); (À.F.); (M.C.); (F.J.P.-C.)
- Nutrition and Food Safety Research Institute (INSA-UB), 08921 Santa Coloma de Gramenet, Spain
| | - Malén Massot-Cladera
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (C.M.-F.); (I.A.-B.); (M.M.-C.); (À.F.); (M.C.); (F.J.P.-C.)
- Nutrition and Food Safety Research Institute (INSA-UB), 08921 Santa Coloma de Gramenet, Spain
| | - Sebastian Tims
- Danone Nutricia Research, 3584 CT Utrecht, The Netherlands; (S.T.); (K.K.); (J.G.); (J.K.)
| | - Karen Knipping
- Danone Nutricia Research, 3584 CT Utrecht, The Netherlands; (S.T.); (K.K.); (J.G.); (J.K.)
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CA Utrecht, The Netherlands
| | - Johan Garssen
- Danone Nutricia Research, 3584 CT Utrecht, The Netherlands; (S.T.); (K.K.); (J.G.); (J.K.)
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CA Utrecht, The Netherlands
| | - Jan Knol
- Danone Nutricia Research, 3584 CT Utrecht, The Netherlands; (S.T.); (K.K.); (J.G.); (J.K.)
- Laboratory of Microbiology, Wageningen University, 6708 PB Wageningen, The Netherlands
| | - Àngels Franch
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (C.M.-F.); (I.A.-B.); (M.M.-C.); (À.F.); (M.C.); (F.J.P.-C.)
- Nutrition and Food Safety Research Institute (INSA-UB), 08921 Santa Coloma de Gramenet, Spain
| | - Margarida Castell
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (C.M.-F.); (I.A.-B.); (M.M.-C.); (À.F.); (M.C.); (F.J.P.-C.)
- Nutrition and Food Safety Research Institute (INSA-UB), 08921 Santa Coloma de Gramenet, Spain
| | - María J. Rodríguez-Lagunas
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (C.M.-F.); (I.A.-B.); (M.M.-C.); (À.F.); (M.C.); (F.J.P.-C.)
- Nutrition and Food Safety Research Institute (INSA-UB), 08921 Santa Coloma de Gramenet, Spain
| | - Francisco J. Pérez-Cano
- Physiology Section, Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Science, University of Barcelona (UB), 08028 Barcelona, Spain; (C.M.-F.); (I.A.-B.); (M.M.-C.); (À.F.); (M.C.); (F.J.P.-C.)
- Nutrition and Food Safety Research Institute (INSA-UB), 08921 Santa Coloma de Gramenet, Spain
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24
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Sharif S, Oddie SJ, Heath PT, McGuire W. Prebiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Hippokratia 2021. [DOI: 10.1002/14651858.cd015133] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Sahar Sharif
- Centre for Reviews and Dissemination; University of York; York UK
| | - Sam J Oddie
- Bradford Neonatology; Bradford Teaching Hospitals NHS Foundation Trust; Bradford UK
| | - Paul T Heath
- Division of Child Health and Vaccine Institute; St. George's, University of London; London UK
| | - William McGuire
- Centre for Reviews and Dissemination; University of York; York UK
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25
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Pabari K, Pithva S, Kothari C, Purama RK, Kondepudi KK, Vyas BRM, Kothari R, Ambalam P. Evaluation of Probiotic Properties and Prebiotic Utilization Potential of Weissella paramesenteroides Isolated From Fruits. Probiotics Antimicrob Proteins 2021; 12:1126-1138. [PMID: 31942681 DOI: 10.1007/s12602-019-09630-w] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Weissella paramesenteroides has gained a considerable attention as bacteriocin and exopolysaccharide producers. However, potential of W. paramesenteroides to utilize different prebiotics is unexplored area of research. Fruits being vectors of various probiotics, five W. paramesenteroides strains, namely, FX1, FX2, FX5, FX9, and FX12, were isolated from different fruits. They were screened and selected based on their ability to survive at pH 2.5 and in 1.0% sodium taurocholate, high cell surface hydrophobicity, mucin adhesion, bile-induced biofilm formation, antimicrobial activity (AMA) against selected enteropathogens, and prebiotic utilization ability, implicating the functional properties of these strains. In vitro safety evaluation showed that strains were susceptible to antibiotics except vancomycin and did not harbor any virulent traits such as biogenic amine production, hemolysis, and DNase production. Based on their functionality, two strains FX5 and FX9 were selected for prebiotic utilization studies by thin layer chromatography (TLC) and short-chain fatty acids (SCFAs) production by high performance liquid chromatography. TLC profile evinced the ability of these two strains to utilize low molecular weight galactooligosaccharides (GOS) and fructooligosaccharides (FOS), as only the upper low molecular weight fractions were disappeared from cell-free-supernatants (CFS). Enhanced β-galactosidase activity correlated with galactose accumulation in residual CFS of GOS displayed GOS utilization ability. Both the strains exhibited AMA against E. coli and Staph. aureus and high SCFAs production in the presence of prebiotic, suggesting their synbiotic potential. Thus, W. paramesenteroides strains FX5 and FX9 exhibit potential probiotic properties with prebiotic utilization and can be taken forward to evaluate synergistic synbiotic potential in detail.
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Affiliation(s)
- Kinjal Pabari
- Department of Biotechnology, Christ College, Vidya Niketan, Saurashtra University, PO, Rajkot, Gujarat, 360005, India.,UGC-CAS Department of Biosciences, Saurashtra University, Rajkot, Gujarat, 360005, India
| | - Sheetal Pithva
- Government Science College, Sector 15, Gandhinagar, India
| | - Charmy Kothari
- Department of Biotechnology, Christ College, Vidya Niketan, Saurashtra University, PO, Rajkot, Gujarat, 360005, India
| | - Ravi Kiran Purama
- National Institute of Plant Genome Research, Aruna Asaf Marg, Po Box No. 10531, New Delhi, India
| | | | | | - Ramesh Kothari
- UGC-CAS Department of Biosciences, Saurashtra University, Rajkot, Gujarat, 360005, India.
| | - Padma Ambalam
- Department of Biotechnology, Christ College, Vidya Niketan, Saurashtra University, PO, Rajkot, Gujarat, 360005, India.
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26
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The Use of an Amino Acid Formula Containing Synbiotics in Infants with Cow's Milk Protein Allergy-Effect on Clinical Outcomes. Nutrients 2021; 13:nu13072205. [PMID: 34199007 PMCID: PMC8308253 DOI: 10.3390/nu13072205] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 06/11/2021] [Accepted: 06/25/2021] [Indexed: 11/25/2022] Open
Abstract
Cow’s milk protein allergy (CMPA) is common and costly. Clinical trials of infants with CMPA have shown that the use of an amino acid formula containing pre- and probiotics (synbiotics) (AAF-Syn) may lead to significant reductions in infections, medication prescriptions and hospital admissions, compared to AAF without synbiotics. These effects have not yet been confirmed in real-world practice. This retrospective matched cohort study examined clinical and healthcare data from The Health Improvement Network database, from 148 infants with CMPA (54% male, mean age at diagnosis 4.69 months), prescribed either AAF-Syn (probiotic Bifidobacterium breve M16-V and prebiotics, including chicory-derived oligo-fructose and long-chain inulin) or AAF. AAF-Syn was associated with fewer symptoms (−37%, p < 0.001), infections (−35%, p < 0.001), medication prescriptions (−19%, p < 0.001) and healthcare contacts (−18%, p = 0.15) vs. AAF. Infants prescribed AAF-Syn had a significantly higher probability of achieving asymptomatic management without hypoallergenic formula (HAF) (adjusted HR 3.70, 95% CI 1.97–6.95, p < 0.001), with a shorter clinical course of symptoms (median time to asymptomatic management without HAF 1.35 years vs. 1.95 years). AAF-Syn was associated with potential cost-savings of £452.18 per infant over the clinical course of symptoms. These findings may be attributable to the effect of the specific synbiotic on the gut microbiome. Further research is warranted to explore this. This real-world study provides evidence consistent with clinical trials that AAF-Syn may produce clinical and healthcare benefits with potential economic impact.
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27
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Engevik MA, Danhof HA, Hall A, Engevik KA, Horvath TD, Haidacher SJ, Hoch KM, Endres BT, Bajaj M, Garey KW, Britton RA, Spinler JK, Haag AM, Versalovic J. The metabolic profile of Bifidobacterium dentium reflects its status as a human gut commensal. BMC Microbiol 2021; 21:154. [PMID: 34030655 PMCID: PMC8145834 DOI: 10.1186/s12866-021-02166-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 03/30/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Bifidobacteria are commensal microbes of the mammalian gastrointestinal tract. In this study, we aimed to identify the intestinal colonization mechanisms and key metabolic pathways implemented by Bifidobacterium dentium. RESULTS B. dentium displayed acid resistance, with high viability over a pH range from 4 to 7; findings that correlated to the expression of Na+/H+ antiporters within the B. dentium genome. B. dentium was found to adhere to human MUC2+ mucus and harbor mucin-binding proteins. Using microbial phenotyping microarrays and fully-defined media, we demonstrated that in the absence of glucose, B. dentium could metabolize a variety of nutrient sources. Many of these nutrient sources were plant-based, suggesting that B. dentium can consume dietary substances. In contrast to other bifidobacteria, B. dentium was largely unable to grow on compounds found in human mucus; a finding that was supported by its glycosyl hydrolase (GH) profile. Of the proteins identified in B. dentium by proteomic analysis, a large cohort of proteins were associated with diverse metabolic pathways, indicating metabolic plasticity which supports colonization of the dynamic gastrointestinal environment. CONCLUSIONS Taken together, we conclude that B. dentium is well adapted for commensalism in the gastrointestinal tract.
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Affiliation(s)
- Melinda A Engevik
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA.
- Department of Regernative Medicine & Cell Biology, Medical University of South Carolina, SC, Charleston, USA.
| | - Heather A Danhof
- Department of Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
| | - Anne Hall
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - Kristen A Engevik
- Department of Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
| | - Thomas D Horvath
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - Sigmund J Haidacher
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - Kathleen M Hoch
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - Bradley T Endres
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TX, USA
| | - Meghna Bajaj
- Department of Chemistry and Physics, and Department of Biotechnology, Alcorn State University, Lorman, MS, 39096, USA
| | - Kevin W Garey
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TX, USA
| | - Robert A Britton
- Department of Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
| | - Jennifer K Spinler
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - Anthony M Haag
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - James Versalovic
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
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28
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Abstract
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the effect of enteral supplementation with synbiotics (versus placebo or no treatment, or versus probiotics or prebiotics alone) on the risk of necrotising enterocolitis and associated morbidity and mortality in very preterm or very low birth weight infants.
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29
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Ninchan B, Noidee C. Production and prebiotic properties of oligofructans from sugarcane juice fermentation by Bacillus subtilis TISTR 001. 3 Biotech 2021; 11:213. [PMID: 33928001 PMCID: PMC8039079 DOI: 10.1007/s13205-021-02757-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2021] [Accepted: 03/27/2021] [Indexed: 11/26/2022] Open
Abstract
Oligofructans are potential biological substances that due to their distinctive properties have a positive health-promoting effect. This research aimed to produce oligofructans using sugarcane juice fermentation with Bacillus subtilis TISTR 001 and to study the prebiotic properties in vitro. The results showed that the maximum total oligofructans in the form of free fructose was 2.57% (w/v) at the 84th hour of fermentation with 0.17 g/g reducing sugar and a production yield of 0.031 g/L/h and maximum levansucrase activity of 1.57 × 106 U/mL at that time. The oligofructans contained in the fermented juice had potential functional ingredients that exhibited prebiotic properties that could resist the digestion of enzymes in the gastrointestinal tract under in vitro conditions with digestion of only 6.92%. In addition, the fermented juice promoted the growth of prebiotics, especially Bifidobacterium bifidum TISTR 2129 and inhibited the growth of pathogens using both single culturing and co-culturing with probiotics.
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Affiliation(s)
- Boontiwa Ninchan
- Department of Biotechnology, Faculty of Agro-Industry, Kasetsart University, Bangkok, 10900 Thailand
| | - Chanyanuch Noidee
- Department of Biotechnology, Faculty of Agro-Industry, Kasetsart University, Bangkok, 10900 Thailand
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30
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Schultz G, Alexander R, Lima FV, Giordano RC, Ribeiro MP. Kinetic modeling of the enzymatic synthesis of galacto-oligosaccharides: Describing galactobiose formation. FOOD AND BIOPRODUCTS PROCESSING 2021. [DOI: 10.1016/j.fbp.2021.02.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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31
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Vandenplas Y, Hegar B, Munasir Z, Astawan M, Juffrie M, Bardosono S, Sekartini R, Basrowi RW, Wasito E. The role of soy plant-based formula supplemented with dietary fiber to support children's growth and development: An expert opinion. Nutrition 2021; 90:111278. [PMID: 34004412 DOI: 10.1016/j.nut.2021.111278] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 03/05/2021] [Accepted: 04/01/2021] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Soy-based formula has evolved in usage and processing technology since its introduction in 1909, and has been used as substitute formula for infants or children with cow milk allergy since 1929. At present, personal opinions, religious background, availability, palatability, and cost are part of the reasons soy-based formula is chosen. Technology in processing soy-based formula has evolved from using soy flour to soy protein isolate, which provides advantages. However, concerns remain regarding the impact of its use on the growth and development of children. METHODS An expert meeting, attended by 12 experts, was initiated in Jakarta, Indonesia, to obtain an evidence-based consensus on the role of soy protein isolate formula, as well as its nutritional value to support growth and development. RESULTS Ensuring that plant-based formula (i.e., soy protein isolate formula) is fortified with key nutrients, such as calcium, iron, and dietary fiber is important. CONCLUSIONS Consensus was achieved, concluding that soy protein isolate formula is safe, affordable, and an alternative option for cow's milk-based formula for term infants.
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Affiliation(s)
- Yvan Vandenplas
- KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Belgium.
| | - Badriul Hegar
- Department of Pediatric, Faculty of Medicine, Universitas Indonesia; Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Zakiudin Munasir
- Department of Pediatric, Faculty of Medicine, Universitas Indonesia; Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | - Made Astawan
- Department of Food Science and Technology, IPB University, Bogor, Indonesia
| | - Mohammad Juffrie
- Department of Child Health, Faculty of Medicine, Universitas Gajah Mada, Yogyakarta, Indonesia
| | - Saptawati Bardosono
- Department of Nutrition, Faculty of Medicine, Universitas Indonesia; Cipto Mangunkusumo General Hospital; Jakarta, Indonesia
| | - Rini Sekartini
- Department of Pediatric, Faculty of Medicine, Universitas Indonesia; Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
| | | | - Erika Wasito
- Danone Specialized Nutrition Indonesia, Jakarta, Indonesia
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Long-Term Safety and Efficacy of Prebiotic Enriched Infant Formula-A Randomized Controlled Trial. Nutrients 2021; 13:nu13041276. [PMID: 33924514 PMCID: PMC8070502 DOI: 10.3390/nu13041276] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 04/07/2021] [Accepted: 04/09/2021] [Indexed: 01/15/2023] Open
Abstract
The present study aims to evaluate the effects of an infant formula supplemented with a mixture of prebiotic short and long chain inulin-type oligosaccharides on health outcomes, safety and tolerance, as well as on fecal microbiota composition during the first year of life. In a prospective, multicenter, randomized, double-blind study, n = 160 healthy term infants under 4 months of age were randomized to receive either an infant formula enriched with 0.8 g/dL of Orafti®Synergy1 or an unsupplemented control formula until the age of 12 months. Growth, fever (>38 °C) and infections were regularly followed up by a pediatrician. Digestive symptoms, stool consistency as well as crying and sleeping patterns were recorded during one week each study month. Fecal microbiota and immunological biomarkers were determined from a subgroup of infants after 2, 6 and 12 months of life. The intention to treat (ITT) population consisted of n = 149 infants. Both formulae were well tolerated. Mean duration of infections was significantly lower in the prebiotic fed infants (p < 0.05). The prebiotic group showed higher Bifidobacterium counts at month 6 (p = 0.006), and higher proportions of Bifidobacterium in relation to total bacteria at month 2 and 6 (p = 0.042 and p = 0.013, respectively). Stools of infants receiving the prebiotic formula were softer (p < 0.05). Orafti®Synergy1 tended to beneficially impact total daily amount of crying (p = 0.0594). Supplementation with inulin-type prebiotic oligosaccharides during the first year of life beneficially modulates the infant gut microbiota towards higher Bifidobacterium levels at the first 6 months of life, and is associated with reduced duration of infections.
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Sorensen K, Cawood AL, Gibson GR, Cooke LH, Stratton RJ. Amino Acid Formula Containing Synbiotics in Infants with Cow's Milk Protein Allergy: A Systematic Review and Meta-Analysis. Nutrients 2021; 13:935. [PMID: 33799379 PMCID: PMC7998621 DOI: 10.3390/nu13030935] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/08/2021] [Accepted: 03/10/2021] [Indexed: 12/15/2022] Open
Abstract
Cow's milk protein allergy (CMPA) is associated with dysbiosis of the infant gut microbiome, with allergic and immune development implications. Studies show benefits of combining synbiotics with hypoallergenic formulae, although evidence has never been systematically examined. This review identified seven publications of four randomised controlled trials comparing an amino acid formula (AAF) with an AAF containing synbiotics (AAF-Syn) in infants with CMPA (mean age 8.6 months; 68% male, mean intervention 27.3 weeks, n = 410). AAF and AAF-Syn were equally effective in managing allergic symptoms and promoting normal growth. Compared to AAF, significantly fewer infants fed AAF-Syn had infections (OR 0.35 (95% CI 0.19-0.67), p = 0.001). Overall medication use, including antibacterials and antifectives, was lower among infants fed AAF-Syn. Significantly fewer infants had hospital admissions with AAF-Syn compared to AAF (8.8% vs. 20.2%, p = 0.036; 56% reduction), leading to potential cost savings per infant of £164.05-£338.77. AAF-Syn was associated with increased bifidobacteria (difference in means 31.75, 95% CI 26.04-37.45, p < 0.0001); reduced Eubacterium rectale and Clostridium coccoides (difference in means -19.06, 95% CI -23.15 to -14.97, p < 0.0001); and reduced microbial diversity (p < 0.05), similar to that described in healthy breastfed infants, and may be associated with the improved clinical outcomes described. This review provides evidence that suggests combining synbiotics with AAF produces clinical benefits with potential economic implications.
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Affiliation(s)
- Katy Sorensen
- Medical Affairs, Nutricia Ltd., White Horse Business Park, Trowbridge BA14 0XQ, UK
| | - Abbie L. Cawood
- Medical Affairs, Nutricia Ltd., White Horse Business Park, Trowbridge BA14 0XQ, UK
- Institute of Human Nutrition, Faculty of Medicine, Mailpoint 113, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK; (A.L.C.); (R.J.S.)
| | - Glenn R. Gibson
- Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading RG6 6AP, UK;
| | - Lisa H. Cooke
- Department of Nutrition and Dietetics, Bristol Royal Hospital for Children, Upper Maudlin Street, Bristol BS2 8BJ, UK;
| | - Rebecca J. Stratton
- Medical Affairs, Nutricia Ltd., White Horse Business Park, Trowbridge BA14 0XQ, UK
- Institute of Human Nutrition, Faculty of Medicine, Mailpoint 113, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK; (A.L.C.); (R.J.S.)
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Gallier S, Van den Abbeele P, Prosser C. Comparison of the Bifidogenic Effects of Goat and Cow Milk-Based Infant Formulas to Human Breast Milk in an in vitro Gut Model for 3-Month-Old Infants. Front Nutr 2020; 7:608495. [PMID: 33363198 PMCID: PMC7759547 DOI: 10.3389/fnut.2020.608495] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Accepted: 11/20/2020] [Indexed: 12/12/2022] Open
Abstract
Human milk contains prebiotic components, such as human milk oligosaccharides (HMOs), which stimulate the growth of specific members of the infant gut microbiota (e.g., Bifidobacteria). Plant-based or synthetic oligosaccharides are often added to infant formulas to simulate the bifidogenic effect of HMOs. Cow milk, the most common source of protein in infant formula, and goat milk, used increasingly in the manufacture of infant formula, contain naturally-occurring prebiotics. This study compared the upper gastrointestinal digestion and subsequent colonic fermentation of human milk vs. goat and cow milk-based infant formulas (goat IF and cow IF, respectively), without additional oligosaccharides using an in vitro model for 3-month-old infants based on the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®). First, a dialysis approach using 3.5 kDa membranes was demonstrated to simulate small intestinal absorption of carbohydrates in conditions similar to those in vivo. During the in vitro digestion experiment, oligosaccharides were detected in human milk and goat IF but barely detected in the cow IF. Further, all three milk matrices decreased colonic pH by boosting acetate, lactate, and propionate production, which related to increased abundances of acetate/lactate-producing Bifidobacteriaceae for human milk (+25.7%) and especially goat IF (33.8%) and cow IF (37.7%). Only cow IF stimulated butyrate production which correlated with an increase in Lachnospiraceae and Clostridiaceae. Finally, Enterobacteriaceae and Acidaminococcaceae also increased with all three milk matrices, while production of proteolytic metabolites (branched-chain fatty acids) was only detected for the cow IF. Overall, goat and cow milk-based formulas without added oligosaccharides impacted gut microbial activity and composition similarly to human milk. This suggests that even without supplementation of formula with oligosaccharides, whole goat milk, whole cow milk and cow milk ingredients already supply compounds in formulas that exert beneficial bifidogenic effects. Further clinical research is warranted to elucidate the effect of whole goat milk-based formulas on the infant gut microbiome.
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Affiliation(s)
| | | | - Colin Prosser
- Dairy Goat Co-operative (NZ) Ltd, Hamilton, New Zealand
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Like mother, like microbe: human milk oligosaccharide mediated microbiome symbiosis. Biochem Soc Trans 2020; 48:1139-1151. [PMID: 32597470 DOI: 10.1042/bst20191144] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 06/07/2020] [Accepted: 06/08/2020] [Indexed: 02/07/2023]
Abstract
Starting shortly after parturition, and continuing throughout our lifetime, the gut microbiota coevolves with our metabolic and neurological programming. This symbiosis is regulated by a complex interplay between the host and environmental factors, including diet and lifestyle. Not surprisingly, the development of this microbial community is of critical importance to health and wellness. In this targeted review, we examine the gut microbiome from birth to 2 years of age to characterize the role human milk oligosaccharides play in early formation of microbial flora.
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Sanchez-Siles LM, Bernal MJ, Gil D, Bodenstab S, Haro-Vicente JF, Klerks M, Plaza-Diaz J, Gil Á. Are Sugar-Reduced and Whole Grain Infant Cereals Sensorially Accepted at Weaning? A Randomized Controlled Cross-Over Trial. Nutrients 2020; 12:1883. [PMID: 32599738 PMCID: PMC7353261 DOI: 10.3390/nu12061883] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/19/2020] [Accepted: 06/22/2020] [Indexed: 01/10/2023] Open
Abstract
The way infants are fed during the complementary period can have a significant impact on infants' health and development. Infant cereals play an important role in complementary feeding in many countries. In spite of well documented benefits of a low sugar and high whole grain diet, commercial infant cereals are often refined and contain a high amount of sugars. The aim of the present study was to compare the sensory acceptability, gastrointestinal tolerance and bowel habits of two commercially available infant cereals in Spain with varying sugar and whole grain contents in infants at weaning. Forty-six healthy infants (mean age = 5.2 ± 0.4 months) received one of the two infant cereals containing either 0% whole grain flour and a high sugar content produced by starch hydrolysis (24 g/100 g) (Cereal A) or 50% whole grain flour and a medium-sugar content produced by hydrolysis (12 g/100 g) (Cereal B) in a randomized, triple blind, cross-over controlled trial. Both types of infant cereals were consumed for seven weeks. The cross-over was carried out after seven weeks. Sensory acceptability, anthropometry, gastrointestinal tolerance and adverse events were measured, and results evaluated using a linear regression model. No significant differences were observed between groups in any of the main variables analyzed. Importantly, the long-term health implications of our findings represent a wake-up call for the food industry to reduce or even eliminate simple sugars in infant cereals and for regulatory bodies and professional organizations to recommend whole grain infant cereals.
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Affiliation(s)
- Luis Manuel Sanchez-Siles
- Research and Nutrition Lab, Hero Group, 30820 Murcia, Spain; (M.J.B.); (J.F.H.-V.); (M.K.)
- Institute for Research and Nutrition, Hero Group, 5600 Lenzburg, Switzerland;
| | - Maria Jose Bernal
- Research and Nutrition Lab, Hero Group, 30820 Murcia, Spain; (M.J.B.); (J.F.H.-V.); (M.K.)
| | - David Gil
- Pediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital Clínico Universitario Virgen de la Arrixaca, 30120 Murcia, Spain;
| | - Stefan Bodenstab
- Institute for Research and Nutrition, Hero Group, 5600 Lenzburg, Switzerland;
| | | | - Michelle Klerks
- Research and Nutrition Lab, Hero Group, 30820 Murcia, Spain; (M.J.B.); (J.F.H.-V.); (M.K.)
| | - Julio Plaza-Diaz
- Institute of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n., 18016 Armilla, Granada, Spain; (J.P.-D.); (Á.G.)
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain
- ibs.GRANADA, Instituto de Investigación Biosanitaria, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
| | - Ángel Gil
- Institute of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, Avda. del Conocimiento s/n., 18016 Armilla, Granada, Spain; (J.P.-D.); (Á.G.)
- Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, Spain
- ibs.GRANADA, Instituto de Investigación Biosanitaria, Complejo Hospitalario Universitario de Granada, 18014 Granada, Spain
- CIBEROBN (CIBER Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, 28029 Madrid, Spain
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Engevik MA, Luk B, Chang-Graham AL, Hall A, Herrmann B, Ruan W, Endres BT, Shi Z, Garey KW, Hyser JM, Versalovic J. Bifidobacterium dentium Fortifies the Intestinal Mucus Layer via Autophagy and Calcium Signaling Pathways. mBio 2019; 10:e01087-19. [PMID: 31213556 PMCID: PMC6581858 DOI: 10.1128/mbio.01087-19] [Citation(s) in RCA: 171] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 05/11/2019] [Indexed: 02/07/2023] Open
Abstract
Much remains unknown about how the intestinal microbiome interfaces with the protective intestinal mucus layer. Bifidobacterium species colonize the intestinal mucus layer and can modulate mucus production by goblet cells. However, select Bifidobacterium strains can also degrade protective glycans on mucin proteins. We hypothesized that the human-derived species Bifidobacterium dentium would increase intestinal mucus synthesis and expulsion, without extensive degradation of mucin glycans. In silico data revealed that B. dentium lacked the enzymes necessary to extensively degrade mucin glycans. This finding was confirmed by demonstrating that B. dentium could not use naive mucin glycans as primary carbon sources in vitro To examine B. dentium mucus modulation in vivo, Swiss Webster germfree mice were monoassociated with live or heat-killed B. dentium Live B. dentium-monoassociated mice exhibited increased colonic expression of goblet cell markers Krüppel-like factor 4 (Klf4), Trefoil factor 3 (Tff3), Relm-β, Muc2, and several glycosyltransferases compared to both heat-killed B. dentium and germfree counterparts. Likewise, live B. dentium-monoassociated colon had increased acidic mucin-filled goblet cells, as denoted by Periodic Acid-Schiff-Alcian Blue (PAS-AB) staining and MUC2 immunostaining. In vitro, B. dentium-secreted products, including acetate, were able to increase MUC2 levels in T84 cells. We also identified that B. dentium-secreted products, such as γ-aminobutyric acid (GABA), stimulated autophagy-mediated calcium signaling and MUC2 release. This work illustrates that B. dentium is capable of enhancing the intestinal mucus layer and goblet cell function via upregulation of gene expression and autophagy signaling pathways, with a net increase in mucin production.IMPORTANCE Microbe-host interactions in the intestine occur along the mucus-covered epithelium. In the gastrointestinal tract, mucus is composed of glycan-covered proteins, or mucins, which are secreted by goblet cells to form a protective gel-like structure above the epithelium. Low levels of mucin or alterations in mucin glycans are associated with inflammation and colitis in mice and humans. Although current literature links microbes to the modulation of goblet cells and mucins, the molecular pathways involved are not yet fully understood. Using a combination of gnotobiotic mice and mucus-secreting cell lines, we have identified a human-derived microbe, Bifidobacterium dentium, which adheres to intestinal mucus and secretes metabolites that upregulate the major mucin MUC2 and modulate goblet cell function. Unlike other Bifidobacterium species, B. dentium does not extensively degrade mucin glycans and cannot grow on mucin alone. This work points to the potential of using B. dentium and similar mucin-friendly microbes as therapeutic agents for intestinal disorders with disruptions in the mucus barrier.
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Affiliation(s)
- Melinda A Engevik
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
| | - Berkley Luk
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
| | - Alexandra L Chang-Graham
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Anne Hall
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
| | - Beatrice Herrmann
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
| | - Wenly Ruan
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
| | - Bradley T Endres
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA
| | - Zhongcheng Shi
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
| | - Kevin W Garey
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA
| | - Joseph M Hyser
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - James Versalovic
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
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Rigo-Adrover MDM, Knipping K, Garssen J, van Limpt K, Knol J, Franch À, Castell M, Rodríguez-Lagunas MJ, Pérez-Cano FJ. Prevention of Rotavirus Diarrhea in Suckling Rats by a Specific Fermented Milk Concentrate with Prebiotic Mixture. Nutrients 2019; 11:nu11010189. [PMID: 30669251 PMCID: PMC6356616 DOI: 10.3390/nu11010189] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 01/14/2019] [Accepted: 01/14/2019] [Indexed: 01/18/2023] Open
Abstract
Several microbial modulatory concepts, such as certain probiotics and prebiotics, confer protection against gastrointestinal infections, among which is acute diarrhea caused by the rotavirus (RV). Other microbiota modulators, such as postbiotics, produced during fermentation, might also have the potential to counteract RV infection. In light of this, a fermented milk, made by using Bifidobacterium breve C50 (BbC50) and Streptococcus thermophilus 065 (St065) with a prebiotic mixture-short chain galactooligosaccharides/long chain fructooligosaccharides (scGOS/lcFOS 9:1)-with potential to impact the intestinal microbiota composition was tested. An RV infected rat model was used to evaluate the amelioration of the infectious process and the improvement of the immune response induced by the fermented milk with prebiotic mixture. The dietary intervention caused a reduction in the clinical symptoms of diarrhea, such as severity and incidence. Furthermore, a modulation of the immune response was observed, which might enhance the reduction of the associated diarrhea. In addition, the fermented milk with prebiotic mixture was able to bind the virus and reduce its clearance. In conclusion, the postbiotic components in the fermented milk in combination with the prebiotics used here showed protective properties against RV infection.
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Affiliation(s)
- Maria Del Mar Rigo-Adrover
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, University of Barcelona (UB), Av. Joan XXIII 27-31, 08028 Barcelona, Spain.
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), C/ Prat de la Riba 171, Santa Coloma de Gramanet, 08921 Barcelona, Spain.
| | - Karen Knipping
- Danone Nutricia Research, 3584 Utrecht, The Netherlands.
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3512 Utrecht, The Netherlands.
| | - Johan Garssen
- Danone Nutricia Research, 3584 Utrecht, The Netherlands.
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3512 Utrecht, The Netherlands.
| | - Kees van Limpt
- Danone Nutricia Research, 3584 Utrecht, The Netherlands.
| | - Jan Knol
- Danone Nutricia Research, 3584 Utrecht, The Netherlands.
| | - Àngels Franch
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, University of Barcelona (UB), Av. Joan XXIII 27-31, 08028 Barcelona, Spain.
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), C/ Prat de la Riba 171, Santa Coloma de Gramanet, 08921 Barcelona, Spain.
| | - Margarida Castell
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, University of Barcelona (UB), Av. Joan XXIII 27-31, 08028 Barcelona, Spain.
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), C/ Prat de la Riba 171, Santa Coloma de Gramanet, 08921 Barcelona, Spain.
| | - Maria J Rodríguez-Lagunas
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, University of Barcelona (UB), Av. Joan XXIII 27-31, 08028 Barcelona, Spain.
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), C/ Prat de la Riba 171, Santa Coloma de Gramanet, 08921 Barcelona, Spain.
| | - Francisco J Pérez-Cano
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, University of Barcelona (UB), Av. Joan XXIII 27-31, 08028 Barcelona, Spain.
- Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), C/ Prat de la Riba 171, Santa Coloma de Gramanet, 08921 Barcelona, Spain.
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Oswari H, Widodo AD, Handayani F, Juffrie M, Sundjaya T, Bindels J, Hegar B. Dosage-Related Prebiotic Effects of Inulin in Formula-Fed Infants. Pediatr Gastroenterol Hepatol Nutr 2019; 22:63-71. [PMID: 30671375 PMCID: PMC6333587 DOI: 10.5223/pghn.2019.22.1.63] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 08/30/2018] [Accepted: 09/12/2018] [Indexed: 12/02/2022] Open
Abstract
PURPOSE The aim of this study was to identify the minimally meaningful dosage of inulin leading to a prebiotic effect in Indonesian infants. METHODS In a randomized controlled double-blinded, parallel, 3-arm intervention study, 164 healthy formula-fed infants aged 3 to 5 months first obtained formula-A (without inulin) during a 4-week adaptation period. Subsequently, 142 subjects were subjected to a 4-week feeding period by administering either formula-A (no inulin), formula-B (0.2 g/100 mL inulin) or formula-C (0.4 g/100 mL inulin). The primary outcome parameter was %-bifidobacteria in faecal samples determined using quantitative polymerase chain reaction analyses. Secondary outcome parameters were faecal %-lactobacilli, pH and stool frequency, and consistency. Growth and tolerance/adverse effects were recorded as safety parameters. RESULTS Typical %-bifidobacteria and %-lactobacilli at the end of the adaptation period in the study population were 14% and 2%, respectively. For faecal pH, significant differences between formula groups A vs. C and A vs. B were found at the end of the intervention period. Testing for differences in faecal %-bifidobacteria and %-lactobacilli between groups was hampered by non-normal data set distributions; no statistically significant differences were obtained. Comparisons within groups revealed that only in formula group C, all the three relevant parameters exhibited a significant effect with an increase in faecal %-bifidobacteria and %-lactobacilli and a decrease in pH. CONCLUSION A consistent prebiotic effect along with a decrease in pH and increase in %-bifidobacteria and %-lactobacilli was found only in the group administered 0.4 g inulin/100 mL.
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Affiliation(s)
- Hanifah Oswari
- Department of Child Health, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.,Research Task Force, Indonesian Pediatric Society (IDAI), Jakarta, Indonesia
| | - Ariani Dewi Widodo
- Research Task Force, Indonesian Pediatric Society (IDAI), Jakarta, Indonesia
| | - Frieda Handayani
- Research Task Force, Indonesian Pediatric Society (IDAI), Jakarta, Indonesia
| | - Mohammad Juffrie
- Research Task Force, Indonesian Pediatric Society (IDAI), Jakarta, Indonesia.,Department of Pediatrics, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Tonny Sundjaya
- Danone Nutricia Early Life Nutrition R&D, Jakarta, Indonesia
| | - Jacques Bindels
- Nutricia Research, Danone Nutricia Early Life Nutrition, Singapore, Singapore
| | - Badriul Hegar
- Department of Child Health, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.,Research Task Force, Indonesian Pediatric Society (IDAI), Jakarta, Indonesia
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Abstract
The intestinal microbiome plays a crucial role in the development of the immune system and regulation of immune responses. Many factors influence the composition of the infant intestinal microbiome and therefore the development and function of the immune system. This, in turn, may alter the risk of subsequent allergies, autoimmune diseases and other adverse health outcomes. Here, we review factors that influence the composition of the intestinal microbiome during the first year of life, including birth location, gestational age, delivery mode, feeding method, hospitalization, antibiotic or probiotic intake and living conditions. Understanding how the early intestinal microbiome is established and how this is perturbed provides many opportunities for interventions to improve health.
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Randomized, Double-Blind, Placebo-Controlled Parallel Clinical Trial Assessing the Effect of Fructooligosaccharides in Infants with Constipation. Nutrients 2018; 10:nu10111602. [PMID: 30388751 PMCID: PMC6266108 DOI: 10.3390/nu10111602] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2018] [Revised: 10/25/2018] [Accepted: 10/26/2018] [Indexed: 01/29/2023] Open
Abstract
Constipation often begins in the first year of life. The aim of this study was to assess the effect of fructooligosaccharides (FOS) in the treatment of infants with constipation. This randomized, double-blind, placebo-controlled clinical trial included infants with constipation who were randomly assigned to one of two parallel groups: FOS or placebo. Either the FOS supplement or the placebo was added to the infant formula. Thirty-six infants completed the 4-week intervention. Therapeutic success occurred in 83.3% of the FOS group infants and in 55.6% of the control group infants (p = 0.073; one-tailed test). Compared with the control group, the FOS group exhibited a higher frequency of softer stools (p = 0.035) and fewer episodes of straining and/or difficulty passing stools (p = 0.041). At the end of the intervention, the mouth-to-anus transit time was shorter (22.4 and 24.5 h, p = 0.035), and the Bifidobacterium sp. count was higher (p = 0.006) in the FOS group. In conclusion, the use of FOS in infants with constipation was associated with significant improvement in symptoms, but the results showed no statistical significance regarding the success of the therapy compared with the control group. FOS was associated with reduced bowel transit time and higher counts of the genus Bifidobacterium in the stool.
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42
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Targeting the gut microbiota to influence brain development and function in early life. Neurosci Biobehav Rev 2018; 95:191-201. [PMID: 30195933 DOI: 10.1016/j.neubiorev.2018.09.002] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 09/03/2018] [Accepted: 09/04/2018] [Indexed: 12/16/2022]
Abstract
In the first 2-3 years of life, the gut microbiota of infants quickly becomes diverse and rich. Disruptions in the evolving gut microbiota during this critical developmental period can impact brain development. Communication between the microbiota, gut and brain is driven by hormonal and neural regulation, as well as immune and metabolic pathways, however, our understanding of how the parallel developments that may underlie this communication are limited. In this paper, we review the known associations between the gut microbiota and brain development and brain function in early life, speculate on the potential mechanisms involved in this complex relationship and describe how nutritional intervention can further modulate the microbiota and, ultimately, brain development and function.
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Shahramian I, Kalvandi G, Javaherizadeh H, Khalili M, Noori NM, Delaramnasab M, Bazi A. The effects of prebiotic supplementation on weight gain, diarrhoea, constipation, fever and respiratory tract infections in the first year of life. J Paediatr Child Health 2018; 54:875-880. [PMID: 29579345 DOI: 10.1111/jpc.13906] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2017] [Revised: 01/28/2018] [Accepted: 02/22/2018] [Indexed: 11/28/2022]
Abstract
AIM This study was conducted to evaluate the effect of prebiotics on some common clinical ailments in healthy term infants. METHODS Sixty healthy-term, breastfed (BF) infants were included. Along with these infants, 120 healthy-term formula-fed infants were randomly assigned to either the prebiotic formula (PF, n = 60) or regular formula (RF, n = 60) groups. Ready-to-use prebiotic-supplemented formula containing galacto-oligosaccharides and polydextrose (ratio 1:1) was used. RESULTS At 2 months of age, PF infants demonstrated significantly higher weight gain than BF and RF. At 6 months of age, bodyweight was significantly higher in the RF group compared to BF and PF groups (P < 0.05). Similar results were seen at 8, 10 and 12 months of age. At 10 months of age, the duration of diarrhoea was significantly shorter in PF-fed compared to the RF (P = 0.03) group. A significant difference was found between PF and RF (P < 0.0001) and BF and RF groups (P = 0.002) for diarrhoea duration. Means of constipation episodes per year were 0.03 ± 0.18, 0.433 ± 0.77 and 0.1 ± 0.30 for the BF, RF and PF groups, respectively, with significant difference found between BF and RF (P = 0.006) and PF and RF (P = 0.02). The means of episodes of respiratory tract infections per year for BF, RF and PF groups were 1 ± 0.69, 1.6 ± 0.88 and 1 ± 0.58, respectively (P = 0.01). CONCLUSION Prebiotic-supplemented and regular formula were similar to breast milk regarding prophylactic effects for diarrhoea, constipation and respiratory tract infections in the first year of life. Prebiotic-supplemented formula may be an appropriate substitution for breast milk when breast milk in unavailable.
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Affiliation(s)
- Iraj Shahramian
- Pediatric Digestive and Hepatic Research Center, Zabol University of Medical Sciences, Zabol, Iran
| | | | - Hazhir Javaherizadeh
- Department of Pediatric Gastroenterology, Abuzar Children's Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Manijeh Khalili
- Children and Adolescent Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Noor Mohammad Noori
- Children and Adolescent Health Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Mojtaba Delaramnasab
- Clinical Research Development Unit, Amir-Al-Momenin Hospital, Zabol University of Medical Sciences, Zabol, Iran
| | - Ali Bazi
- Pediatric Digestive and Hepatic Research Center, Zabol University of Medical Sciences, Zabol, Iran.,Clinical Research Development Unit, Amir-Al-Momenin Hospital, Zabol University of Medical Sciences, Zabol, Iran
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Lohner S, Jakobik V, Mihályi K, Soldi S, Vasileiadis S, Theis S, Sailer M, Sieland C, Berényi K, Boehm G, Decsi T. Inulin-Type Fructan Supplementation of 3- to 6-Year-Old Children Is Associated with Higher Fecal Bifidobacterium Concentrations and Fewer Febrile Episodes Requiring Medical Attention. J Nutr 2018; 148:1300-1308. [PMID: 29982534 PMCID: PMC6074834 DOI: 10.1093/jn/nxy120] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 05/16/2018] [Indexed: 11/14/2022] Open
Abstract
Background Inulin-type fructans used in formula have been shown to promote microbiota composition and stool consistency closer to those of breastfed infants and to have beneficial effects on fever occurrence, diarrhea, and incidence of infections requiring antibiotic treatment in infants. Objectives The primary study aim was to explore whether prophylactic supplementation with prebiotic fructans is able to influence the frequency of infectious diseases in kindergarten children during a winter period. A secondary objective was to ascertain the effect on the intestinal microbiota. Methods 142 boys and 128 girls aged 3-6 y were randomly allocated to consume 6 g/d fructans or maltodextrin for 24 wk. At baseline, stool samples were collected for microbiota analysis and anthropometric measurements were made. During the intervention period diagnoses were recorded by physicians, whereas disease symptoms, kindergarten absenteeism, dietary habits, and stool consistency were recorded by parents. Baseline measurements were repeated at wk 24. Results In total 219 children finished the study. Both the relative abundance of Bifidobacterium (P < 0.001) and that of Lactobacillus (P = 0.014) were 19.9% and 7.8% higher, respectively, post data normalization, in stool samples of children receiving fructans as compared with those of controls at wk 24. This was accompanied by significantly softer stools within the normal range in the prebiotic group from wk 12 onwards. The incidence of febrile episodes requiring medical attention [0.65 ± 1.09 compared with 0.9 ± 1.11 infections/(24 wk × child), P = 0.04] and that of sinusitis (0.01 ± 0.1 compared with 0.06 ± 0.25, P = 0.03) were significantly lower in the prebiotic group. The number of infectious episodes and their duration reported by parents did not differ significantly between the 2 intervention groups. Conclusions Prebiotic supplementation modified the composition of the intestinal microbiota and resulted in softer stools in kindergarten-aged children. The reduction in febrile episodes requiring medical attention supports the concept of further studies on prebiotics in young children. This trial was registered at clinicaltrials.gov as NCT03241355.
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Affiliation(s)
- Szimonetta Lohner
- Department of Paediatrics, Clinical Center of the University of Pécs,Address correspondence to SL (e-mail: )
| | - Viktória Jakobik
- Department of Paediatrics, Clinical Center of the University of Pécs
| | - Krisztina Mihályi
- Department of Paediatrics, Clinical Center of the University of Pécs
| | - Sara Soldi
- Advanced Analytical Technologies Srl, Fiorenzualo d'Arda (Pc), Italy
| | - Sotirios Vasileiadis
- Department of Biochemistry & Biotechnology, University of Thessaly, Larissa, Greece
| | | | | | | | - Károly Berényi
- Department of Public Health Medicine, Medical School, University of Pécs, Pécs, Hungary
| | | | - Tamás Decsi
- Department of Paediatrics, Clinical Center of the University of Pécs
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45
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Cuello-Garcia C, Fiocchi A, Pawankar R, Yepes-Nuñez JJ, Morgano GP, Zhang Y, Agarwal A, Gandhi S, Terracciano L, Schünemann HJ, Brozek JL. Prebiotics for the prevention of allergies: A systematic review and meta-analysis of randomized controlled trials. Clin Exp Allergy 2018; 47:1468-1477. [PMID: 29035013 DOI: 10.1111/cea.13042] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2017] [Revised: 09/07/2017] [Accepted: 09/12/2017] [Indexed: 12/22/2022]
Abstract
BACKGROUND Prevalence of allergic diseases in infants is approximately 10% reaching 20 to 30% in those with an allergic first-degree relative. Prebiotics are selectively fermented food ingredients that allow specific changes in composition/activity of the gastrointestinal microflora. They modulate immune responses, and their supplementation has been proposed as an intervention to prevent allergies. OBJECTIVE To assess in pregnant women, breastfeeding mothers, and infants (populations) the effect of supplementing prebiotics (intervention) versus no prebiotics (comparison) on the development of allergic diseases and to inform the World Allergy Organization guidelines. METHODS We performed a systematic review of studies assessing the effects of prebiotic supplementation with an intention to prevent the development of allergies. RESULTS Of 446 unique records published until November 2016 in Cochrane, MEDLINE, and EMBASE, 22 studies fulfilled a priori specified criteria. We did not find any studies of prebiotics given to pregnant women or breastfeeding mothers. Prebiotic supplementation in infants, compared to placebo, had the following effects: risk of developing eczema (RR: 0.68, 95% CI: 0.40 to 1.15), wheezing/asthma (RR, 0.37; 95% CI: 0.17 to 0.80), and food allergy (RR: 0.28, 95% CI: 0.08 to 1.00). There was no evidence of an increased risk of any adverse effects (RR: 1.01, 95% CI: 0.92 to 1.10). Prebiotic supplementation had little influence growth rate (MD: 0.92 g per day faster with prebiotics, 95% CI: 0 to 1.84) and the final infant weight (MD: 0.10 kg higher with prebiotics, 95% CI: -0.09 to 0.29). The certainty of these estimates is very low due to risk of bias and imprecision of the results. CONCLUSIONS Currently available evidence on prebiotic supplementation to reduce the risk of developing allergies is very uncertain.
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Affiliation(s)
- C Cuello-Garcia
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
| | - A Fiocchi
- Pediatric Hospital Bambino Gesù, Rome, Italy
| | - R Pawankar
- Department of Pediatrics, Nippon Medical School, Tokyo, Japan
| | - J J Yepes-Nuñez
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.,University of Antioquia School of Medicine, Medellín, Colombia
| | - G P Morgano
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
| | - Y Zhang
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
| | - A Agarwal
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - S Gandhi
- Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - L Terracciano
- Department of Child and Maternal Medicine, University of Milan Medical School at the Melloni Hospital, Milan, Italy
| | - H J Schünemann
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
| | - J L Brozek
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada
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Rigo-Adrover MDM, van Limpt K, Knipping K, Garssen J, Knol J, Costabile A, Franch À, Castell M, Pérez-Cano FJ. Preventive Effect of a Synbiotic Combination of Galacto- and Fructooligosaccharides Mixture With Bifidobacterium breve M-16V in a Model of Multiple Rotavirus Infections. Front Immunol 2018; 9:1318. [PMID: 29942312 PMCID: PMC6004411 DOI: 10.3389/fimmu.2018.01318] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 05/28/2018] [Indexed: 12/24/2022] Open
Abstract
Rotavirus (RV) causes morbidity and mortality among infants worldwide, and there is evidence that probiotics and prebiotics can have a positive influence against infective processes such as that due to RV. The aim of this study was to evidence a preventive role of one prebiotic mixture (of short-chain galactooligosaccharide/long-chain fructooligosaccharide), the probiotic Bifidobacterium breve M-16V and the combination of the prebiotic and the probiotic, as a synbiotic, in a suckling rat double-RV infection model. Hyperimmune bovine colostrum was used as protection control. The first infection was induced with RV SA11 and the second one with EDIM. Clinical variables and immune response were evaluated after both infections. Dietary interventions ameliorated clinical symptoms after the first infection. The prebiotic and the synbiotic significantly reduced viral shedding after the first infection, but all the interventions showed higher viral load than in the RV group after the second infection. All interventions modulated ex vivo antibody and cytokine production, gut wash cytokine levels and small intestine gene expression after both infections. In conclusion, a daily supplement of the products tested in this preclinical model is highly effective in preventing RV-induced diarrhea but allowing the boost of the early immune response for a future immune response against reinfection, suggesting that these components may be potential agents for modulating RV infection in infants.
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Affiliation(s)
- Maria Del Mar Rigo-Adrover
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, University of Barcelona (UB), Barcelona, Spain.,Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), University of Barcelona (UB), Santa Coloma de Gramanet, Spain
| | | | - Karen Knipping
- Nutricia Research, Utrecht, Netherlands.,Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - Johan Garssen
- Nutricia Research, Utrecht, Netherlands.,Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - Jan Knol
- Nutricia Research, Utrecht, Netherlands
| | - Adele Costabile
- Health Sciences Research Centre, Life Science Department, Whitelands College, University of Roehampton, London, United Kingdom
| | - Àngels Franch
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, University of Barcelona (UB), Barcelona, Spain.,Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), University of Barcelona (UB), Santa Coloma de Gramanet, Spain
| | - Margarida Castell
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, University of Barcelona (UB), Barcelona, Spain.,Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), University of Barcelona (UB), Santa Coloma de Gramanet, Spain
| | - Francisco José Pérez-Cano
- Departament de Bioquímica i Fisiologia, Facultat de Farmàcia i Ciències de l'Alimentació, University of Barcelona (UB), Barcelona, Spain.,Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), University of Barcelona (UB), Santa Coloma de Gramanet, Spain
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47
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Yu L, O'Sullivan D. Immobilization of whole cells of Lactococcus lactis containing high levels of a hyperthermostable β-galactosidase enzyme in chitosan beads for efficient galacto-oligosaccharide production. J Dairy Sci 2018; 101:2974-2983. [DOI: 10.3168/jds.2017-13770] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 12/06/2017] [Indexed: 12/22/2022]
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Candy DCA, Van Ampting MTJ, Oude Nijhuis MM, Wopereis H, Butt AM, Peroni DG, Vandenplas Y, Fox AT, Shah N, West CE, Garssen J, Harthoorn LF, Knol J, Michaelis LJ. A synbiotic-containing amino-acid-based formula improves gut microbiota in non-IgE-mediated allergic infants. Pediatr Res 2018; 83:677-686. [PMID: 29155807 PMCID: PMC6023699 DOI: 10.1038/pr.2017.270] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 10/07/2017] [Indexed: 12/18/2022]
Abstract
BackgroundPrebiotics and probiotics (synbiotics) can modify gut microbiota and have potential in allergy management when combined with amino-acid-based formula (AAF) for infants with cow's milk allergy (CMA).MethodsThis multicenter, double-blind, randomized controlled trial investigated the effects of an AAF-including synbiotic blend on percentages of bifidobacteria and Eubacterium rectale/Clostridium coccoides group (ER/CC) in feces from infants with suspected non-IgE-mediated CMA. Feces from age-matched healthy breastfed infants were used as reference (healthy breastfed reference (HBR)) for primary outcomes. The CMA subjects were randomized and received test or control formula for 8 weeks. Test formula was a hypoallergenic, nutritionally complete AAF including a prebiotic blend of fructo-oligosaccharides and the probiotic strain Bifidobacterium breve M-16V. Control formula was AAF without synbiotics.ResultsA total of 35 (test) and 36 (control) subjects were randomized; HBR included 51 infants. At week 8, the median percentage of bifidobacteria was higher in the test group than in the control group (35.4% vs. 9.7%, respectively; P<0.001), whereas ER/CC was lower (9.5% vs. 24.2%, respectively; P<0.001). HBR levels of bifidobacteria and ER/CC were 55% and 6.5%, respectively.ConclusionAAF including specific synbiotics, which results in levels of bifidobacteria and ER/CC approximating levels in the HBR group, improves the fecal microbiota of infants with suspected non-IgE-mediated CMA.
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Affiliation(s)
| | | | - Manon M Oude Nijhuis
- Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, The Netherlands
| | - Harm Wopereis
- Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
| | - Assad M Butt
- Royal Alexandra Children’s Hospital, Brighton, UK
| | | | | | - Adam T Fox
- Guy’s and St Thomas’ Hospitals NHS Foundation Trust, London, UK
| | - Neil Shah
- Great Ormond Street Hospital, London, UK
| | | | - Johan Garssen
- Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands
| | - Lucien F Harthoorn
- Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, The Netherlands
| | - Jan Knol
- Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, The Netherlands
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Infant formulae supplemented with prebiotics: Are they better than unsupplemented formulae? An updated systematic review. Br J Nutr 2018; 119:810-825. [DOI: 10.1017/s0007114518000120] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
AbstractIn 2011, the Committee on Nutrition of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition systematically reviewed published evidence related to the safety and health effects of the administration of formulae supplemented with pro- and/or prebiotics compared with unsupplemented formulae. We updated evidence on the effects of the administration of prebiotic-supplemented infant formulae (IF) compared with unsupplemented IF. Five databases were searched up to March 2017 for randomised controlled trials. In all, forty-one publications were identified, including twenty-five new publications. The administration of currently evaluated prebiotic-supplemented formulae to healthy infants does not raise safety concerns with regard to growth and adverse effects. Some favourable clinical effects are possible, primarily stool softening, which may be beneficial in some infants. Currently, there is no existing robust evidence to recommend the routine use of prebiotic-supplemented formulae. The latter conclusion may reflect the small amount of data on specific prebiotics and outcomes, rather than a genuine lack of an effect. The efficacy and safety should be considered for each prebiotic(s)-supplemented formula.
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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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