|
1
|
Li F, Hooi SL, Choo YM, Teh CSJ, Toh KY, Lim LWZ, Lee YQ, Chong CW, Ahmad Kamar A. Progression of gut microbiome in preterm infants during the first three months. Sci Rep 2025; 15:12104. [PMID: 40204761 PMCID: PMC11982265 DOI: 10.1038/s41598-025-95198-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 03/19/2025] [Indexed: 04/11/2025] Open
Abstract
The colonization and evolution of gut microbiota early in life play a vital role in shaping a healthy, robust immune system for infant health, whether in combating short-term illness or improving long-term health outcomes. Early-life clinical practices may interrupt or disrupt the normal colonization process of the infant gut microbiota, thereby increasing disease susceptibility. In this prospective cohort study, we analyzed the gut microbiota of 46 term and 23 preterm infants using 16S rRNA gene metagenomic sequencing. Fecal samples were collected at six timepoints during the first three months of life. Notably, gestational age was the main factor contributing to differences in the meconium microbial composition. Intriguingly, our study unveiled a more homogeneous microbial composition in preterm infants with more abundant Bifidobacterium from the postnatal age (PNA) of one month. Concurrently, the beneficial bacteria Bifidobacterium and Lactobacillus gradually increased, and the potentially pathogenic bacteria Clostridium, Enterobacter, Enterococcus, Klebsiella, and Pseudomonas gradually decreased. Furthermore, our study underscored a link between decreased microbial diversity of preterm infants and exclusive breastfeeding and antibiotic exposure. Moreover, preterm infants with patent ductus arteriosus (PDA) exhibited reduced microbial diversity but higher abundances of Streptococcus oralis and Streptococcus mitis.
Collapse
Affiliation(s)
- Fangfang Li
- Department of Pediatrics, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| | | | - Yao Mun Choo
- Department of Pediatrics, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
| | - Cindy Shuan Ju Teh
- Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
| | | | | | - Yee Qing Lee
- Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| | - Chun Wie Chong
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500, Selangor, Malaysia
- Monash Microbiome Research Centre, Monash University Malaysia, Bandar Sunway, 47500, Selangor, Malaysia
| | - Azanna Ahmad Kamar
- Department of Pediatrics, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia
| |
Collapse
|
|
2
|
Wurm J, Curtis N, Zimmermann P. The effect of antibiotics on the intestinal microbiota in children - a systematic review. FRONTIERS IN ALLERGY 2024; 5:1458688. [PMID: 39435363 PMCID: PMC11491438 DOI: 10.3389/falgy.2024.1458688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 09/06/2024] [Indexed: 10/23/2024] Open
Abstract
Background Children are the age group with the highest exposure to antibiotics (ABX). ABX treatment changes the composition of the intestinal microbiota. The first few years of life are crucial for the establishment of a healthy microbiota and consequently, disturbance of the microbiota during this critical period may have far-reaching consequences. In this review, we summarise studies that have investigated the effect of ABX on the composition of the intestinal microbiota in children. Methods According to the PRISMA guidelines, a systematic search was done using MEDLINE and Embase to identify original studies that have investigated the effect of systemic ABX on the composition of the intestinal microbiota in children. Results We identified 89 studies investigating a total of 9,712 children (including 4,574 controls) and 14,845 samples. All ABX investigated resulted in a reduction in alpha diversity, either when comparing samples before and after ABX or children with ABX and controls. Following treatment with penicillins, the decrease in alpha diversity persisted for up to 6-12 months and with macrolides, up to the latest follow-up at 12-24 months. After ABX in the neonatal period, a decrease in alpha diversity was still found at 36 months. Treatment with penicillins, penicillins plus gentamicin, cephalosporins, carbapenems, macrolides, and aminoglycosides, but not trimethoprim/sulfamethoxazole, was associated with decreased abundances of beneficial bacteria including Actinobacteria, Bifidobacteriales, Bifidobacteriaceae, and/or Bifidobacterium, and Lactobacillus. The direction of change in the abundance of Enterobacteriaceae varied with ABX classes, but an increase in Enterobacteriaceae other than Escherichia coli was frequently observed. Conclusion ABX have profound effects on the intestinal microbiota of children, with notable differences between ABX classes. Macrolides have the most substantial impact while trimethoprim/sulfamethoxazole has the least pronounced effect.
Collapse
Affiliation(s)
- Juliane Wurm
- Department of Paediatrics, Fribourg Hospital, Fribourg, Switzerland
- Department of Health Science and Medicine, University Lucerne, Lucerne, Switzerland
| | - Nigel Curtis
- Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia
- Infectious Diseases Research Group, Murdoch Children’s Research Institute, Parkville, VIC, Australia
- Infectious Diseases Unit, The Royal Children’s Hospital Melbourne, Parkville, VIC, Australia
| | - Petra Zimmermann
- Department of Paediatrics, Fribourg Hospital, Fribourg, Switzerland
- Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia
- Infectious Diseases Research Group, Murdoch Children’s Research Institute, Parkville, VIC, Australia
- Department for Community Health, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
| |
Collapse
|
|
3
|
Hutchinson R, Wade W, Millar M, Ansbro K, Stacey F, Costeloe K, Fleming P. Changes in the intestinal microbiome of the preterm baby associated with stopping non-invasive pressure support: a prospective cohort study. BMJ Paediatr Open 2024; 8:e002675. [PMID: 39362793 PMCID: PMC11459353 DOI: 10.1136/bmjpo-2024-002675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Accepted: 09/09/2024] [Indexed: 10/05/2024] Open
Abstract
BACKGROUND Intestinal dysbiosis is implicated in the pathogenesis of necrotising enterocolitis and late-onset sepsis in preterm babies. The provision of non-invasive positive pressure ventilation is a common clinical intervention in preterm babies, and may be hypothesised to adversely affect intestinal bacterial growth, through increased aerophagia and induction of a hyperoxic intestinal environment; however this relationship has not been previously well characterised. METHODOLOGY In this prospectively recruited cohort study, high-throughput 16S rRNA gene sequencing was combined with contemporaneous clinical data collection, to assess within-subject changes in microbiome development around the time of transitioning from non-invasive positive pressure respiratory support to unsupported spontaneous breathing. RESULTS In a group of 14 preterm infants, bacterial diversity was seen to increase by 0.34 units/week (inverse Simpson index) at the point of transitioning off non-invasive positive pressure respiratory support. Correspondingly, a significant increase in anaerobic genera (Bifidobacteria spp, Veillonella spp), and a non-significant fall in Enterobacteriaceae was also seen at this time. CONCLUSIONS Provision of non-invasive positive pressure ventilation is associated with suppression of both diversity accrual and obligate anaerobic growth in the preterm intestine. This has clinical implications in view of the widespread use of non-invasive positive pressure ventilation in preterm neonatal care (and wider adult use), and demonstrates the need for potential strategies (eg, probiotic support; reduced aerophagia) to support the development of a healthy gut microbiome during this time.
Collapse
Affiliation(s)
- Richard Hutchinson
- Queen Mary University of London, London, UK
- Department of Neonatology, Homerton University Hospital NHS Foundation Trust, London, UK
| | - William Wade
- King's College London, London, UK
- The Forsyth Institute, Cambridge, Massachusetts, USA
| | | | | | - Fiona Stacey
- Department of Neonatology, Homerton University Hospital NHS Foundation Trust, London, UK
| | - Kate Costeloe
- Department of Neonatology, Homerton University Hospital NHS Foundation Trust, London, UK
- Genomics and Child Health, Queen Mary University of London Barts and The London School of Medicine and Dentistry, London, UK
| | - Paul Fleming
- Department of Neonatology, Homerton University Hospital NHS Foundation Trust, London, UK
- Genomics and Child Health, Queen Mary University of London Barts and The London School of Medicine and Dentistry, London, UK
| |
Collapse
|
|
4
|
Masi AC, Beck LC, Perry JD, Granger CL, Hiorns A, Young GR, Bode L, Embleton ND, Berrington JE, Stewart CJ. Human milk microbiota, oligosaccharide profiles, and infant gut microbiome in preterm infants diagnosed with necrotizing enterocolitis. Cell Rep Med 2024; 5:101708. [PMID: 39216480 PMCID: PMC11524953 DOI: 10.1016/j.xcrm.2024.101708] [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: 04/10/2024] [Revised: 06/25/2024] [Accepted: 08/08/2024] [Indexed: 09/04/2024]
Abstract
Necrotizing enterocolitis (NEC) is a severe intestinal disease of very preterm infants with mother's own milk (MOM) providing protection, but the contribution of the MOM microbiota to NEC risk has not been explored. Here, we analyze MOM of 110 preterm infants (48 NEC, 62 control) in a cross-sectional study. Breast milk contains viable bacteria, but there is no significant difference in MOM microbiota between NEC and controls. Integrative analysis between MOM microbiota, human milk oligosaccharides (HMOs), and the infant gut microbiota shows positive correlations only between Acinetobacter in the infant gut and Acinetobacter and Staphylococcus in MOM. This study suggests that NEC protection from MOM is not modulated through the MOM microbiota. Thus, "'restoring" the MOM microbiota in donor human milk is unlikely to reduce NEC, and emphasis should instead focus on increasing fresh maternal human milk intake and researching different therapies for NEC prevention.
Collapse
Affiliation(s)
- Andrea C Masi
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - Lauren C Beck
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - John D Perry
- Microbiology Department, Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK
| | - Claire L Granger
- Newcastle Neonatal Service, Newcastle Hospitals NHS Trust, Newcastle upon Tyne NE1 4LP, UK
| | - Alice Hiorns
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - Gregory R Young
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - Lars Bode
- Department of Pediatrics, Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (MOMI CORE), University of California San Diego, La Jolla, CA 92093, USA; The Human Milk Institute (HMI), University of California San Diego, La Jolla, CA 92093, USA
| | - Nicholas D Embleton
- Newcastle Neonatal Service, Newcastle Hospitals NHS Trust, Newcastle upon Tyne NE1 4LP, UK; Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - Janet E Berrington
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Newcastle Neonatal Service, Newcastle Hospitals NHS Trust, Newcastle upon Tyne NE1 4LP, UK.
| | - Christopher J Stewart
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
| |
Collapse
|
|
5
|
Turunen J, Tejesvi MV, Paalanne N, Pokka T, Amatya SB, Mishra S, Kaisanlahti A, Reunanen J, Tapiainen T. Investigating prenatal and perinatal factors on meconium microbiota: a systematic review and cohort study. Pediatr Res 2024; 95:135-145. [PMID: 37591927 PMCID: PMC10798900 DOI: 10.1038/s41390-023-02783-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 06/30/2023] [Accepted: 07/29/2023] [Indexed: 08/19/2023]
Abstract
BACKGROUND The first-pass meconium has been suggested as a proxy for the fetal gut microbiota because it is formed in utero. This systematic review and cohort study investigated how pre- and perinatal factors influence the composition of the meconium microbiota. METHODS We performed the systematic review using Covidence by searching PubMed, Scopus, and Web of Science databases with the search terms "meconium microbiome" and "meconium microbiota". In the cohort study, we performed 16 S rRNA gene sequencing on 393 meconium samples and analyzed the sequencing data using QIIME2. RESULTS Our systematic review identified 69 studies exploring prenatal factors, immediate perinatal factors, and microbial composition in relation to subsequent health of infants but gave only limited comparative evidence regarding factors related to the composition of the meconium microbiota. The cohort study pointed to a low-biomass microbiota consisting of the phyla Firmicutes, Proteobacteria and Actinobacteriota and the genera Staphylococcus, Escherichia-Shigella and Lactobacillus, and indicated that immediate perinatal factors affected the composition of the meconium microbiota more than did prenatal factors. CONCLUSIONS This finding supports the idea that the meconium microbiota mostly starts developing during delivery. IMPACT It is unclear when the first-pass meconium microbiota develops, and what are the sources of the colonization. In this systematic review, we found 69 studies exploring prenatal factors, immediate perinatal factors, and microbial composition relative to subsequent health of infants, but there was no consensus on the factors affecting the meconium microbiota development. In this cohort study, immediate perinatal factors markedly affected the meconium microbiota development while prenatal factors had little effect on it. As the meconium microbiota composition was influenced by immediate perinatal factors, the present study supports the idea that the initial gut microbiota develops mainly during delivery.
Collapse
Affiliation(s)
- Jenni Turunen
- Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland.
- Biocenter Oulu, University of Oulu, Oulu, Finland.
| | - Mysore V Tejesvi
- Biocenter Oulu, University of Oulu, Oulu, Finland
- Ecology and Genetics, Faculty of Science, University of Oulu, Oulu, Finland
| | - Niko Paalanne
- Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland
- Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
| | - Tytti Pokka
- Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland
- Research Service Unit, Oulu University Hospital, Oulu, Finland
| | - Sajeen Bahadur Amatya
- Biocenter Oulu, University of Oulu, Oulu, Finland
- Research Unit of Translational Medicine, University of Oulu, Oulu, Finland
| | - Surbhi Mishra
- Biocenter Oulu, University of Oulu, Oulu, Finland
- Research Unit of Translational Medicine, University of Oulu, Oulu, Finland
| | - Anna Kaisanlahti
- Biocenter Oulu, University of Oulu, Oulu, Finland
- Research Unit of Translational Medicine, University of Oulu, Oulu, Finland
| | - Justus Reunanen
- Biocenter Oulu, University of Oulu, Oulu, Finland
- Research Unit of Translational Medicine, University of Oulu, Oulu, Finland
| | - Terhi Tapiainen
- Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland
- Biocenter Oulu, University of Oulu, Oulu, Finland
- Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
| |
Collapse
|
|
6
|
Luoto R, Pärtty A, Vogt JK, Rautava S, Isolauri E. Reversible aberrancies in gut microbiome of moderate and late preterm infants: results from a randomized, controlled trial. Gut Microbes 2023; 15:2283913. [PMID: 38010080 PMCID: PMC10730193 DOI: 10.1080/19490976.2023.2283913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 11/12/2023] [Indexed: 11/29/2023] Open
Abstract
The aim of this study was to obtain insight into the composition and function of the deviant gut microbiome throughout infancy in children born moderately and late preterm and their response to microbiome modulation. We characterized the longitudinal development of the gut microbiome from birth to the age of 12 months by metagenomic sequencing in 43 moderate and late preterm children participating in a randomized, controlled trial (ClinicalTrials.gov/no.NCT00167700) assessing the impact of a probiotic (Lactobacillus rhamnosus GG, ATCC 53,103, currently Lacticaseibacillus rhamnosus GG) and a prebiotic (galacto-oligosaccharide and polydextrose mixture, 1:1) intervention as compared to a placebo administered from 3 to 60 days of life. In addition, 9 full-term, vaginally delivered, breast-fed infants, who remained healthy long-term were included as references. Significant differences in taxonomy, but not in functional potential, were found when comparing the gut microbiome composition of preterm and full-term infants during the first month of life. However, the gut microbiome of preterm infants resembled that of full-term infants by 6 months age. Probiotic and prebiotic treatments were found to mitigate the shift in the microbiome of preterm infants by accelerating Bifidobacteria-dominated gut microbiome in beta diversity analysis. This study provides intriguing information regarding the establishment of the gut microbiome in children born moderately and late preterm, representing the majority of children born preterm. Specific pro- and prebiotics may reverse the proinflammatory gut microbiome composition during the vulnerable period, when the microbiome is low in resilience and susceptible to environmental exposure and simultaneously promotes immunological and metabolic maturation.
Collapse
Affiliation(s)
- Raakel Luoto
- Department of Pediatrics and Adolescent medicine, Turku University Hospital, Turku, Finland
- Institute of Clinical Medicine, University of Turku, Turku, Finland
| | - Anna Pärtty
- Department of Pediatrics and Adolescent medicine, Turku University Hospital, Turku, Finland
- Institute of Clinical Medicine, University of Turku, Turku, Finland
| | | | - Samuli Rautava
- Institute of Clinical Medicine, University of Turku, Turku, Finland
- New Children’s Hospital, Helsinki University Hospital, Helsinki, Finland
| | - Erika Isolauri
- Department of Pediatrics and Adolescent medicine, Turku University Hospital, Turku, Finland
- Institute of Clinical Medicine, University of Turku, Turku, Finland
| |
Collapse
|
|
7
|
Stanikova A, Jouza M, Bohosova J, Slaby O, Jabandziev P. Role of the microbiome in pathophysiology of necrotising enterocolitis in preterm neonates. BMJ Paediatr Open 2023; 7:e002172. [PMID: 37918941 PMCID: PMC10626796 DOI: 10.1136/bmjpo-2023-002172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Accepted: 09/26/2023] [Indexed: 11/04/2023] Open
Abstract
Although necrotising enterocolitis (NEC) is a serious, life-threatening disease, improved neonatal care is increasing the number of survivors with NEC among extremely preterm neonates. Therapy is nevertheless mostly symptomatic and the mortality rate remains high, especially among neonates requiring surgery. Therefore, it is important to focus on preventing the disease and modifiable risk factors. NEC's pathophysiology is multifaceted, with key factors being immaturity of the immune and barrier protective mechanisms of the premature gut and exaggerated proinflammatory reaction to insults like gut hypoxia, enteral nutrition or microbial dysbiosis. The role of the intestinal microbiome in the pathophysiology of NEC has been a subject of research for many years, but to date no specific pathogen or type of dysbiosis has been connected with NEC development. This review assesses current knowledge as to the role of the intestinal microbiota in the pathophysiology of NEC and the possibilities for positively influencing it.
Collapse
Affiliation(s)
- Andrea Stanikova
- Department of Neonatology, University Hospital Brno, Brno, Czech Republic
- Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Martin Jouza
- Faculty of Medicine, Masaryk University, Brno, Czech Republic
- Department of Pediatrics, University Hospital Brno, Brno, Czech Republic
| | - Julia Bohosova
- Central European Institute of Technology, Masaryk University, Brno, Czech Republic
| | - Ondrej Slaby
- Central European Institute of Technology, Masaryk University, Brno, Czech Republic
- Department of Biology, University Hospital Brno, Brno, Czech Republic
| | - Petr Jabandziev
- Faculty of Medicine, Masaryk University, Brno, Czech Republic
- Department of Pediatrics, University Hospital Brno, Brno, Czech Republic
| |
Collapse
|
|
8
|
Jiang L, Xu J, Cheng SY, Wang Y, Cai W. The gut microbiome and intestinal failure-associated liver disease. Hepatobiliary Pancreat Dis Int 2023; 22:452-457. [PMID: 37453856 DOI: 10.1016/j.hbpd.2023.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Accepted: 07/05/2023] [Indexed: 07/18/2023]
Abstract
Intestinal failure-associated liver disease (IFALD) is a common hepatobiliary complication resulting from long-term parenteral nutrition (PN) in patients with intestinal failure. The spectrum of IFALD ranges from cholestasis, steatosis, portal fibrosis, to cirrhosis. Development of IFALD is a multifactorial process, in which gut dysbiosis plays a critical role in its initiation and progression in conjunction with increased intestinal permeability, activation of hepatic immune responses, and administration of lipid emulsion. Gut microbiota manipulation including pre/probiotics, fecal microbiota transplantation, and antibiotics has been studied in IFALD with varying success. In this review, we summarize current knowledge on the taxonomic and functional changes of gut microbiota in preclinical and clinical studies of IFALD. We also review the function of microbial metabolites and associated signalings in the context of IFALD. By providing microbiota-targeted interventions aiming to optimize PN-induced liver injury, our review provides perspectives for future basic and translational investigations in the field.
Collapse
Affiliation(s)
- Lu Jiang
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Shanghai Institute for Pediatric Research, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
| | - Juan Xu
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
| | - Si-Yang Cheng
- Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
| | - Ying Wang
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
| | - Wei Cai
- Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Shanghai Institute for Pediatric Research, Shanghai 200092, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China; Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
| |
Collapse
|
|
9
|
Jia J, Shuai M, Yan W, Tang Q, Wang B, Tang W, Wang P, Zhang T, Yang S, Zhang Y, Liu Q, Fu Y, Cai W, Zheng JS. Conserved Covarying Gut Microbial Network in Preterm Infants and Childhood Growth During the First 5 Years of Life: A Prospective Cohort Study. Am J Clin Nutr 2023; 118:561-571. [PMID: 37517614 DOI: 10.1016/j.ajcnut.2023.07.019] [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: 05/06/2023] [Revised: 07/19/2023] [Accepted: 07/24/2023] [Indexed: 08/01/2023] Open
Abstract
BACKGROUND Longitudinally conserved microbe-microbe interactions may provide insights to understand the complex dynamic system of early-life gut microbiota among preterm infants. OBJECTIVES We aimed to profile the covarying network of gut microbiota among preterm infants and investigate its potential influence on host growth (2-5 y). METHODS We collected time-series stool samples (n = 717 from children and n = 116 from mothers) among 51 preterm and 51 full-term infants from birth up to 5 y of age and among 53 mothers. The included infants underwent time-series measurements of early-life gut microbiota (0-5 y) and growth (2-5 y) from June 2014 to April 2017. The covarying taxa that exhibited consistent covariation from day 1 to year 5 were defined as conserved features in the development of gut microbiota. Childrens' height-for-age z score (HAZ) and weight-for-age z score were calculated according to World Health Organization Child Growth Standards. RESULTS We observed distinct dynamic patterns of both microbial alpha and beta diversity comparing preterm infants with full-term controls during the very early stage (<3 mo). Moreover, we identified a covarying network containing 10 taxa as a conserved gut microbial feature of these preterm infants from birth to 5 y old. This covarying network was distinctive between preterm and full-term infants before 3 mo of age (P < 0.001) and tended to be similar as the infants grew up. Several covarying taxa of the network during early life (<3 mo) were associated with childhood growth (2-5 y) (eg, Clostridium_sensu_stricto_1 with HAZ, β = -0.32, q < 0.01), and the human milk feeding duration was a main modulating factor. CONCLUSIONS Preterm born children possess conserved and distinct covarying microbiota during very early life, which may have a profound influence on their growth later in life. This trial was registered at clinicaltrials.gov as NCT03373721.
Collapse
Affiliation(s)
- Jie Jia
- Department of Clinical Nutrition, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China; Shanghai Institute of Pediatric Research, Shanghai, China
| | - Menglei Shuai
- School of Life Sciences, Westlake University, Hangzhou, China; Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China
| | - Weihui Yan
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China; Shanghai Institute of Pediatric Research, Shanghai, China; Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qingya Tang
- Department of Clinical Nutrition, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bei Wang
- Department of Obstetrics & Gynecology, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenjing Tang
- Department of Clinical Nutrition, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Panliang Wang
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China; Shanghai Institute of Pediatric Research, Shanghai, China
| | - Tian Zhang
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China; Shanghai Institute of Pediatric Research, Shanghai, China
| | - Shihan Yang
- College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yimeng Zhang
- College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qianruo Liu
- College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuanqing Fu
- School of Life Sciences, Westlake University, Hangzhou, China; Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China.
| | - Wei Cai
- Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China; Shanghai Institute of Pediatric Research, Shanghai, China; Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Ju-Sheng Zheng
- School of Life Sciences, Westlake University, Hangzhou, China; Westlake Intelligent Biomarker Discovery Lab, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, China
| |
Collapse
|
|
10
|
Hutchinson RA, Costeloe KL, Wade WG, Millar MR, Ansbro K, Stacey F, Fleming PF. Intravenous antibiotics in preterm infants have a negative effect upon microbiome development throughout preterm life. Gut Pathog 2023; 15:18. [PMID: 37085896 PMCID: PMC10120188 DOI: 10.1186/s13099-023-00544-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Accepted: 04/09/2023] [Indexed: 04/23/2023] Open
Abstract
BACKGROUND Intestinal dysbiosis is implicated in the origins of necrotising enterocolitis and late-onset sepsis in preterm babies. However, the effect of modulators of bacterial growth (e.g. antibiotics) upon the developing microbiome is not well-characterised. In this prospectively-recruited, retrospectively-classified, case-control study, high-throughput 16S rRNA gene sequencing was combined with contemporaneous clinical data collection, to assess the within-subject relationship between antibiotic administration and microbiome development, in comparison to preterm infants with minimal antibiotic exposure. RESULTS During courses of antibiotics, diversity progression fell in comparison to that seen outside periods of antibiotic use (-0.71units/week vs. + 0.63units/week, p < 0.01); Enterobacteriaceae relative abundance progression conversely rose (+ 10.6%/week vs. -8.9%/week, p < 0.01). After antibiotic cessation, diversity progression remained suppressed (+ 0.2units/week, p = 0.02). CONCLUSIONS Antibiotic use has an acute and longer-lasting impact on the developing preterm intestinal microbiome. This has clinical implications with regard to the contribution of antibiotic use to evolving dysbiosis, and affects the interpretation of existing microbiome studies where this effect modulator is rarely accounted for.
Collapse
Affiliation(s)
- R A Hutchinson
- Queen Mary University of London, London, UK.
- Homerton University Hospital NHS Foundation Trust, London, UK.
| | | | - W G Wade
- Queen Mary University of London, London, UK
- King's College London, London, UK
- The Forsyth Institute, Cambridge, MA, USA
| | - M R Millar
- Queen Mary University of London, London, UK
| | - K Ansbro
- Queen Mary University of London, London, UK
| | - F Stacey
- Homerton University Hospital NHS Foundation Trust, London, UK
| | - P F Fleming
- Queen Mary University of London, London, UK
- Homerton University Hospital NHS Foundation Trust, London, UK
| |
Collapse
|
|
11
|
Guo S, Huang K, Liu R, Sun J, Yin C. Regulation of Gut Microbiota through Breast Milk Feeding Benefits Language and Cognitive Development of Preterm Toddlers. Microorganisms 2023; 11:866. [PMID: 37110289 PMCID: PMC10146954 DOI: 10.3390/microorganisms11040866] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 03/19/2023] [Accepted: 03/22/2023] [Indexed: 03/30/2023] Open
Abstract
Feeding practice is essential to growth and development of preterm toddlers. However, the relationship of feeding mode with gut microbiota and neurodevelopment outcomes of preterm toddlers has not been characterized fully. We conducted this cohort study to assess neurodevelopment outcomes and gut microbiota community structures of preterm toddlers who received either breast milk, formula or mixed feeding. Fifty-five preterm toddlers born <37 weeks and 24 term toddlers were recruited in the study. Bayley III mental and physical index scores were measured among preterm toddlers at 12 ± 2 and 18 ± 2 months corrected age (CA). Gut microbiome composition was analyzed by 16S rRNA gene sequencing in fecal samples collected from all participants at 12 months, 16 months and 20 months after birth. We found exclusive breast milk feeding for over three months in the first six months after birth was associated with significant increase in language composite score at 12 months CA (86 (79,97) vs. 77 (71.75,79), p = 0.008) and both language (106.05 ± 14.68 vs. 90.58 ± 12.25, p = 0.000) and cognitive composite score at 18 months CA (107.17 ± 10.85 vs. 99.00 ± 9.24, p = 0.007). The alpha diversity, beta diversity and composition of gut microbiota from those breastfed preterm toddlers not only resembled healthy term toddlers but also followed similar structure of preterm toddlers with enhanced language and cognitive performance. Our results suggest exclusive breast milk feeding for over three months in preterm toddlers leads to optimal cognitive and language development and well-balanced microbiota.
Collapse
Affiliation(s)
- Shan Guo
- Department of Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
| | - Kaikun Huang
- Department of Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
| | - Ruixia Liu
- Department of Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
| | - Jing Sun
- Institute for Integrated and Intelligent Systems, School of Medicine and Dentistry, Griffith University, Gold Coast, QLD 4215, Australia
| | - Chenghong Yin
- Department of Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
| |
Collapse
|
|
12
|
Cerdó T, García-Santos JA, Rodríguez-Pöhnlein A, García-Ricobaraza M, Nieto-Ruíz A, G. Bermúdez M, Campoy C. Impact of Total Parenteral Nutrition on Gut Microbiota in Pediatric Population Suffering Intestinal Disorders. Nutrients 2022; 14:4691. [PMID: 36364953 PMCID: PMC9658482 DOI: 10.3390/nu14214691] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/01/2022] [Accepted: 11/04/2022] [Indexed: 08/10/2023] Open
Abstract
Parenteral nutrition (PN) is a life-saving therapy providing nutritional support in patients with digestive tract complications, particularly in preterm neonates due to their gut immaturity during the first postnatal weeks. Despite this, PN can also result in several gastrointestinal complications that are the cause or consequence of gut mucosal atrophy and gut microbiota dysbiosis, which may further aggravate gastrointestinal disorders. Consequently, the use of PN presents many unique challenges, notably in terms of the potential role of the gut microbiota on the functional and clinical outcomes associated with the long-term use of PN. In this review, we synthesize the current evidence on the effects of PN on gut microbiome in infants and children suffering from diverse gastrointestinal diseases, including necrotizing enterocolitis (NEC), short bowel syndrome (SBS) and subsequent intestinal failure, liver disease and inflammatory bowel disease (IBD). Moreover, we discuss the potential use of pre-, pro- and/or synbiotics as promising therapeutic strategies to reduce the risk of severe gastrointestinal disorders and mortality. The findings discussed here highlight the need for more well-designed studies, and harmonize the methods and its interpretation, which are critical to better understand the role of the gut microbiota in PN-related diseases and the development of efficient and personalized approaches based on pro- and/or prebiotics.
Collapse
Affiliation(s)
- Tomás Cerdó
- Maimonides Institute for Research in Biomedicine of Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain
| | - José Antonio García-Santos
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Anna Rodríguez-Pöhnlein
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - María García-Ricobaraza
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Ana Nieto-Ruíz
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Mercedes G. Bermúdez
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Cristina Campoy
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
- Spanish Network of Biomedical Research in Epidemiology and Public Health (CIBERESP), Granada’s Node, Carlos III Health Institute, Avda. Monforte de Lemos 5, 28028 Madrid, Spain
| |
Collapse
|
|
13
|
Nasogastric enteral feeding tubes modulate preterm colonization in early life. Pediatr Res 2022; 92:838-847. [PMID: 34845351 DOI: 10.1038/s41390-021-01852-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 10/04/2021] [Accepted: 10/28/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Preterm infants are generally fed through nasogastric enteral feeding tubes (NEFTs). The aim of this work was to evaluate the role of NEFTs in the initial colonization of the preterm gut and its evolution within the first 2 weeks after birth. METHODS For this purpose, fecal and NEFT-derived samples from 30 preterm infants hospitalized in a neonatal intensive care unit (NICU) were collected from birth to the second week of life. Samples were cultivated in ten culture media, including three for the isolation of antibiotic-resistant microorganisms. RESULTS Isolates (561) were identified by 16S ribosomal RNA gene sequencing. Although the first NEFTs inserted into the neonates after birth were rarely colonized, analysis of NEFTs and fecal samples over time revealed a significant increase in bacterial abundance, diversity, and detection frequency. Results showed a parallel colonization between time-matched NEFTs and fecal samples, suggesting an ongoing bidirectional transfer of bacteria from the neonatal gut to the NEFTs and vice versa. CONCLUSIONS In short-term hospitalization, length is by far the determinant factor for the early colonization of preterm infants. As NEFT populations reflect the bacterial populations that are colonizing the preterm in a precise moment, their knowledge could be useful to prevent the dissemination of antibiotic-resistant strains. IMPACT The hospital environment modulates preterm colonization immediately after birth. The colonization of preterm feces and NEFTs occurs in parallel. There is an ongoing bidirectional transfer of microorganisms from the neonatal gut to the NEFTs and vice versa. Bacterial communities inside NEFTs could act as reservoirs of antibiotic resistance genes. NEFT populations reflect the bacteria that are colonizing the preterm at a precise moment.
Collapse
|
|
14
|
Jia Q, Yu X, Chang Y, You Y, Chen Z, Wang Y, Liu B, Chen L, Ma D, Xing Y, Tong X. Dynamic Changes of the Gut Microbiota in Preterm Infants With Different Gestational Age. Front Microbiol 2022; 13:923273. [PMID: 35847070 PMCID: PMC9279133 DOI: 10.3389/fmicb.2022.923273] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 05/30/2022] [Indexed: 11/13/2022] Open
Abstract
The gut microbiota plays a key role in the pathogenesis of diseases affecting preterm infants and gestational age is one of the important factors which affect the gut microbiota of infants. To determine the characteristics of the gut microbiota in preterm infants of different gestational ages from birth to 1 year after birth, we collected 622 fecal samples from neonates of different gestational ages at different time points after birth. According to the gestational ages, the samples were divided into four groups, extremely preterm, very preterm, moderate to late preterm, and term group. Meconium and fecal samples at day 14, 28, 120, and 365 after birth were collected. 16S rRNA sequencing was performed and the composition and structure of the gut microbiota in preterm infants of different gestational age was compared with that of term infants. In our study, alpha diversity of meconium in extremely preterm group was higher than very preterm group, moderate to late preterm group and term group and alpha diversity of meconium in preterm group was decreased with increasing of gestational age. At day 14 to day 120 after birth, alpha diversity of term and moderate to late preterm group were significantly higher than other two preterm groups. However, moderate to late preterm group owned the highest alpha diversity which was higher than term group at day 365 after birth. Besides, the results shown the duration of opportunistic pathogen such as Klebsiella and Enterococcus which dominant colonization was different in different gestational age groups. As well as the probiotics, such as Bifidobacterium, which abundance enriched at different time point in different gestational age groups. We profiled the features of dynamic changes of gut microbiome from different gestational ages infants. The results of our research provide new insights for individualized interventions of specific microbes of preterm infants with different gestational ages at different time points after birth.
Collapse
Affiliation(s)
- Qiong Jia
- Department of Pediatrics, Peking University Third Hospital, Beijing, China
| | - Xue Yu
- School of Public Health, Peking University Health Science Center, Beijing, China
| | - Yanmei Chang
- Department of Pediatrics, Peking University Third Hospital, Beijing, China
| | - Yanxia You
- Department of Pediatrics, Peking University Third Hospital, Beijing, China
| | - Zekun Chen
- School of Public Health, Peking University Health Science Center, Beijing, China
| | - Ying Wang
- School of Public Health, Peking University Health Science Center, Beijing, China
| | - Bin Liu
- National Engineering Center of Dairy for Maternal and Child Health, Beijing Sanyuan Foods Co., Ltd., Beijing, China
| | - Lijun Chen
- National Engineering Center of Dairy for Maternal and Child Health, Beijing Sanyuan Foods Co., Ltd., Beijing, China
| | - Defu Ma
- School of Public Health, Peking University Health Science Center, Beijing, China
| | - Yan Xing
- Department of Pediatrics, Peking University Third Hospital, Beijing, China
| | - Xiaomei Tong
- Department of Pediatrics, Peking University Third Hospital, Beijing, China
| |
Collapse
|
|
15
|
Wang W, Wang Y, Liu Y, Tian X, Chen S, Lu Y, Wu B, Xiao Y, Cai W. Lactobacillus plantarum supplementation alleviates liver and intestinal injury in parenteral nutrition-fed piglets. JPEN J Parenter Enteral Nutr 2022; 46:1932-1943. [PMID: 35730411 DOI: 10.1002/jpen.2429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Revised: 05/28/2022] [Accepted: 06/17/2022] [Indexed: 11/08/2022]
Abstract
OBJECTIVE Long-term parenteral nutrition (PN) causes parenteral nutrition-associated liver disease (PNALD) for which therapeutic approaches are limited. This study aimed to investigate the effects of Lactobacillus plantarum CGMCC 1258 (LP) on liver and intestinal injury in the PN-fed neonatal piglets. METHODS The piglets received PN with or without oral LP for 14 days. The levels of liver enzymes and inflammatory markers were measured using biochemical kits and q-RT-PCR. Serum fibroblast growth factor 19 (FGF19) was detected using an enzyme-linked immunosorbent assay (ELISA). The bile acid profiles in the liver, serum, and intestinal contents were determined using ultraperformance liquid chromatography coupled with mass spectrometry (UPLC-MS). The composition of intestinal bacteria was analyzed with 16S rRNA gene amplicon sequencing. RESULTS LP supplementation was associated with improved markers of liver disease, inflammation, and oxidative stress in PN-fed piglets. Moreover, markers of intestinal injury and inflammation were alleviated by LP in PN-fed piglets. Mechanistically, LP increased the abundance of Lactobacillus in ileal contents and stimulated FGF19 expression in ileal mucosa. Subsequently, it increased the expression of small heterodimer partner (SHP) and inhibited cholesterol 7α-hydroxylase (CYP7A1) expression in the liver. Additionally, LP altered the systemic composition and metabolism of bile acids. CONCLUSIONS LP alleviated liver and intestinal injury in PN-fed neonatal piglets by altering the composition of intestinal bacteria and bile acids. This article is protected by copyright. All rights reserved.
Collapse
Affiliation(s)
- Weipeng Wang
- Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Wang
- Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Shanghai Institute of Pediatric Research, Shanghai, China.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Yang Liu
- Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Xinbei Tian
- Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Shanshan Chen
- Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Lu
- Shanghai Institute of Pediatric Research, Shanghai, China.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Bo Wu
- Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yongtao Xiao
- Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Shanghai Institute of Pediatric Research, Shanghai, China.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| | - Wei Cai
- Division of Pediatric Gastroenterology and Nutrition, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Shanghai Institute of Pediatric Research, Shanghai, China.,Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China
| |
Collapse
|
|
16
|
Development of the Gastrointestinal Tract in Newborns as a Challenge for an Appropriate Nutrition: A Narrative Review. Nutrients 2022; 14:nu14071405. [PMID: 35406018 PMCID: PMC9002905 DOI: 10.3390/nu14071405] [Citation(s) in RCA: 54] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/23/2022] [Accepted: 03/23/2022] [Indexed: 02/07/2023] Open
Abstract
The second and third trimesters of pregnancy are crucial for the anatomical and functional development of the gastrointestinal (GI) tract. If premature birth occurs, the immaturity of the digestive and absorptive processes and of GI motility represent a critical challenge to meet adequate nutritional needs, leading to poor extrauterine growth and to other critical complications. Knowledge of the main developmental stages of the processes involved in the digestion and absorption of proteins, carbohydrates, and lipids, as well as of the maturational phases underlying the development of GI motility, may aid clinicians to optimize the nutritional management of preterm infants. The immaturity of these GI systems and functions may negatively influence the patterns of gut colonization, predisposing to an abnormal microbiome. This, in turn, further contributes to alter the functional, immune, and neural development of the GI tract and, especially in preterm infants, has been associated with an increased risk of severe GI complications, such as necrotizing enterocolitis. Deeper understanding of the physiological colonization patterns in term and preterm infants may support the promotion of these patterns and the avoidance of microbial perturbations associated with the development of several diseases throughout life. This review aims to provide a global overview on the maturational features of the main GI functions and on their implications following preterm birth. We will particularly focus on the developmental differences in intestinal digestion and absorption functionality, motility, gut–brain axis interaction, and microbiomes.
Collapse
|
|
17
|
Bozzi Cionci N, Lucaccioni L, Pietrella E, Ficara M, Spada C, Torelli P, Bedetti L, Lugli L, Di Gioia D, Berardi A. Antibiotic Exposure, Common Morbidities and Main Intestinal Microbial Groups in Very Preterm Neonates: A Pilot Study. Antibiotics (Basel) 2022; 11:237. [PMID: 35203839 PMCID: PMC8868158 DOI: 10.3390/antibiotics11020237] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 02/07/2022] [Accepted: 02/08/2022] [Indexed: 01/27/2023] Open
Abstract
Prematurity exposes newborns to increased risks of infections and it is associated with critical morbidities. Preterm infants often require antibiotic therapies that can affect the correct establishment of gut microbiota. The aim of this study was to investigate targeted intestinal bacteria in preterm neonates with common morbidities and receiving antibiotic treatments of variable duration. Stool samples were collected after birth, at 15, 30 and 90 days of life. qPCR quantification of selected microbial groups (Bifidobacterium spp., Bacteroides fragilis group, Enterobacteriaceae, Clostridium cluster I and total bacteria) was performed and correlation between their levels, the duration of antibiotic treatment and different clinical conditions was studied. An increasing trend over time was observed for all microbial groups, especially for Bifdobacterium spp. Prolonged exposure to antibiotics in the first weeks of life affected Clostridium and B. fragilis levels, but these changes no longer persisted at 90 days of life. Variations of bacterial counts were associated with the length of hospital stay, feeding and mechanical ventilation. Late-onset sepsis and patent ductus arteriosus reduced the counts of Bifidobacterium, whereas B. fragilis was influenced by compromised respiratory conditions. This study can be a start point for the identification of microbial biomarkers associated with some common morbidities and tailored strategies for a healthy microbial development.
Collapse
Affiliation(s)
- Nicole Bozzi Cionci
- Department of Agricultural and Food Sciences, University of Bologna, 40127 Bologna, Italy; (N.B.C.); (D.D.G.)
| | - Laura Lucaccioni
- Pediatric Unit, Department of Medical and Surgical Sciences for Mothers, Children and Adults, University of Modena and Reggio Emilia, 41124 Modena, Italy
| | - Elisa Pietrella
- Pediatric Unit, Department of Medical for Mothers and Children, Ramazzini Hospital, 41012 Carpi, Italy;
| | - Monica Ficara
- Pediatric Unit, Department of Medical for Mothers and Children, Bufalini Hospital, 47521 Cesena, Italy;
| | - Caterina Spada
- Neonatal Intensive Care Unit, Department of Medical for Mothers and Children, Bufalini Hospital, 47521 Cesena, Italy;
| | - Paola Torelli
- Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences for Mothers, Children and Adults, University of Modena and Reggio Emilia, 41124 Modena, Italy; (P.T.); (L.B.); (L.L.); (A.B.)
| | - Luca Bedetti
- Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences for Mothers, Children and Adults, University of Modena and Reggio Emilia, 41124 Modena, Italy; (P.T.); (L.B.); (L.L.); (A.B.)
- PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia, 41124 Modena, Italy
| | - Licia Lugli
- Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences for Mothers, Children and Adults, University of Modena and Reggio Emilia, 41124 Modena, Italy; (P.T.); (L.B.); (L.L.); (A.B.)
| | - Diana Di Gioia
- Department of Agricultural and Food Sciences, University of Bologna, 40127 Bologna, Italy; (N.B.C.); (D.D.G.)
| | - Alberto Berardi
- Neonatal Intensive Care Unit, Department of Medical and Surgical Sciences for Mothers, Children and Adults, University of Modena and Reggio Emilia, 41124 Modena, Italy; (P.T.); (L.B.); (L.L.); (A.B.)
| |
Collapse
|
|
18
|
Ahearn-Ford S, Berrington JE, Stewart CJ. Development of the gut microbiome in early life. Exp Physiol 2022; 107:415-421. [PMID: 35041771 PMCID: PMC9305283 DOI: 10.1113/ep089919] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 01/07/2022] [Indexed: 11/28/2022]
Abstract
New Findings
What is the topic of this review? The importance of the early life gut microbiome, with a focus on preterm infants and microbially related diseases. Current techniques to study the preterm gut microbiome are appraised, and the potential of recent methodological advancements is discussed. What advances does it highlight? Recent findings in the field achieved by the application of advanced technologies, the applicability of intestinally derived organoid models to study host–microbiome interactions in the preterm gut, and recent developments in enhancing the physiological relevance of such models. Preterm intestinally derived organoids may provide novel insights into the mechanisms underlying preterm disease, as well as diagnosis and treatment opportunities. These models have huge translational potential, offering a step towards precision medicine. Abstract Accumulating evidence affirms the importance of the gut microbiome in both health and disease. In early life, there exists a critical period in which the composition of gut microbes is particularly malleable and subject to a wide range of influencing factors. Disturbances to microbial communities during this time may be beneficial or detrimental to short and long‐term health outcomes. For infants born prematurely, naïve immune systems, immature gastrointestinal tracts and additional clinical needs put this population at high risk of abnormal microbial colonisation, resulting in increased susceptibility to diseases including necrotising enterocolitis (NEC) and late‐onset sepsis (LOS). Traditional cell culture methods, gnotobiotic animals, molecular sequencing techniques (16S rRNA gene sequencing and metagenomics) and advanced ‘omics’ technologies (transcriptomics, proteomics and metabolomics) have been fundamental in exploring the associations between diet, gut microbes, microbial functions and disease. Despite significant investment and ongoing research efforts, prevention and treatment strategies in NEC and LOS remain limited. Recent endeavours have focused on searching for new, more physiologically relevant models to simulate the preterm intestine. Preterm intestinally derived organoids represent a promising in vitro approach in the study of host–microbiome interactions in the preterm infant gut, offering new and exciting possibilities in this field.
Collapse
Affiliation(s)
- Sinead Ahearn-Ford
- Clinical and Translational Research Institute, Newcastle University, Newcastle, NE2 4HH, UK
| | - Janet E Berrington
- Clinical and Translational Research Institute, Newcastle University, Newcastle, NE2 4HH, UK.,Newcastle Neonatal Service, Newcastle Hospitals NHS Trust, Newcastle, NE1 4LP, UK
| | - Christopher J Stewart
- Clinical and Translational Research Institute, Newcastle University, Newcastle, NE2 4HH, UK
| |
Collapse
|
|
19
|
Healy DB, Ryan CA, Ross RP, Stanton C, Dempsey EM. Clinical implications of preterm infant gut microbiome development. Nat Microbiol 2022; 7:22-33. [PMID: 34949830 DOI: 10.1038/s41564-021-01025-4] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 11/12/2021] [Indexed: 12/12/2022]
Abstract
Perturbations to the infant gut microbiome during the first weeks to months of life affect growth, development and health. In particular, assembly of an altered intestinal microbiota during infant development results in an increased risk of immune and metabolic diseases that can persist into childhood and potentially into adulthood. Most research into gut microbiome development has focused on full-term babies, but health-related outcomes are also important for preterm babies. The systemic physiological immaturity of very preterm gestation babies (born earlier than 32 weeks gestation) results in numerous other microbiome-organ interactions, the mechanisms of which have yet to be fully elucidated or in some cases even considered. In this Perspective, we compare assembly of the intestinal microbiome in preterm and term infants. We focus in particular on the clinical implications of preterm infant gut microbiome composition and discuss the prospects for microbiome diagnostics and interventions to improve the health of preterm babies.
Collapse
Affiliation(s)
- David B Healy
- APC Microbiome Ireland, University College Cork, Cork, Ireland. .,Department of Paediatrics and Child Health, University College Cork, Cork, Ireland.
| | - C Anthony Ryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
| | - R Paul Ross
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Catherine Stanton
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Teagasc Food Research Centre, Moorepark, Fermoy, Ireland
| | - Eugene M Dempsey
- APC Microbiome Ireland, University College Cork, Cork, Ireland.,Department of Paediatrics and Child Health, University College Cork, Cork, Ireland.,INFANT Research Centre, Cork University Hospital, Cork, Ireland
| |
Collapse
|
|
20
|
Skinner AM, Narchi H. Preterm nutrition and neurodevelopmental outcomes. World J Methodol 2021; 11:278-293. [PMID: 34888181 PMCID: PMC8613713 DOI: 10.5662/wjm.v11.i6.278] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 07/13/2021] [Accepted: 09/27/2021] [Indexed: 02/06/2023] Open
Abstract
Survival of preterm infants has been steadily improving in recent years because of many recent advances in perinatal and neonatal medicine. Despite these advances, the growth of survivors does not reach the ideal target level of the normal fetus of the same gestational age. Postnatal weight gain is often not achieved because extrauterine growth has higher energy requirements than intrauterine growth, due to the intensive care environment, illness and inadequate nutrition. Although many other factors influence infant brain development, including family socioeconomic and educational background, the role of nutrition is considerable and fortunately, amenable to intervention. In the preterm neonate, the brain is the most metabolically demanding organ, consuming the largest proportions of energy and nutrient intake for its function and programmed growth and maturation. Weight gain, linear and head circumference growth are all markers of nutritional status and are independently associated with long-term neurodevelopment. Brain development is not only the result of nutrients intake, but in addition, of the interaction with growth factors which depend on adequate nutrient supply and overall health status. This explains why conditions such as sepsis, necrotizing enterocolitis and chronic lung disease alter the distribution and accretion of nutrients thereby suppressing growth factor synthesis. In this review, we will focus on the direct role of nutrition on neurodevelopment, emphasizing why it should be started without delay. The nutritional requirements of the preterm infant will be discussed, followed by the effects of general nutritional interventions and specific nutrients, as well as the role of nutritional supplements on neurodevelopment. The primordial role of human breast milk, breast milk fortifiers and human milk oligosaccharides will be discussed in detail. We will also examine the role of nutrition in preventing neonatal complications which can affect neurodevelopment in their own right.
Collapse
Affiliation(s)
- Alyson Margaret Skinner
- Department of Paediatrics, Manor Hospital, Walsall Healthcare NHS Trust, Walsall WS2 9PS, West Midlands, United Kingdom
- Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain PO Box 17666, United Arab Emirates
| | - Hassib Narchi
- Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain PO Box 17666, United Arab Emirates
| |
Collapse
|
|
21
|
Yang K, He S, Dong W. Gut microbiota and bronchopulmonary dysplasia. Pediatr Pulmonol 2021; 56:2460-2470. [PMID: 34077996 DOI: 10.1002/ppul.25508] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 05/02/2021] [Accepted: 05/16/2021] [Indexed: 12/20/2022]
Abstract
Bronchopulmonary dysplasia is a relatively common and severe complication of prematurity, and its pathogenesis remains ambiguous. Revolutionary advances in microbiological analysis techniques, together with the growing sophistication of the gut-lung axis hypothesis, have resulted in more studies linking gut microbiota dysbiosis to the occurrence and development of bronchopulmonary dysplasia. The present article builds on current findings to examine the intrinsic associations between gut microbiota and bronchopulmonary dysplasia. Gut microbiota dysbiosis may insult the intestinal barrier, triggering inflammation, metabolic disturbances, and malnutrition, consequences of which might impact bronchopulmonary dysplasia by altering the gut-lung axis. By evaluating the potential mechanisms, new therapeutic targets and potential therapeutic modalities for bronchopulmonary dysplasia can be identified from a microecological perspective.
Collapse
Affiliation(s)
- Kun Yang
- Department of Pediatrics, Division of Neonatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.,Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.,Sichuan Clinical Research Center for Birth Defects, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Shasha He
- Department of Pediatrics, Division of Neonatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.,Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.,Sichuan Clinical Research Center for Birth Defects, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Wenbin Dong
- Department of Pediatrics, Division of Neonatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.,Department of Perinatology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.,Sichuan Clinical Research Center for Birth Defects, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| |
Collapse
|
|
22
|
Abstract
Scientists have invested considerable resources in the study of the microbiota of the human body. These microorganisms play pivotal roles in immunity and disease. Of which, probiotics are live beneficial microorganisms that keep your intestinal or lung microbiota healthy, and occupy a special role in combating the infections. Thus, it is critical to understand their contributions to these processes. Technology can facilitate advanced studies of the microbiota, including how it develops and its positive and negatives effects on the immune system. This paper investigates how several factors (e.g. birth delivery mode, metabolic activities, types of microorganisms, and immune system interactions) affect the microbiota, particularly in early life. The paper also discusses how gastrointestinal microbes in particular may be associated with certain disease processes, such as those related to schizophrenia, autism, and diabetes. Clinical studies show that certain probiotic strains, like Lactobacillus rhamnosus GG and Bifidobacterium animalis ssp. lactis help to prevent infection of pathogenic organisms (both bacterial and viral). This research may yield crucial contributions to disease prevention and public health. The dysbiosis may result in changes in the acquired immunity later on. The probiotic strains can prevent viral replication during SARS-CoV-2 or COVID-19 infection by reducing proinflammatory cytokines. There has been much interest into the intestinal flora as proposed by the diversity, volume, and proposed role in disease. Future research in the field of microbiome should be done in order to uncover their association to gut virome by noting both their influence on each other and relevant health and disease.
Collapse
|
|
23
|
Herd-Level and Individual Differences in Fecal Lactobacilli Dynamics of Growing Pigs. Animals (Basel) 2021; 11:ani11010113. [PMID: 33430499 PMCID: PMC7827896 DOI: 10.3390/ani11010113] [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: 12/11/2020] [Revised: 12/28/2020] [Accepted: 12/29/2020] [Indexed: 01/01/2023] Open
Abstract
Simple Summary Selection for hyper-prolific sows has led to increased litter size, decreased birth weight, and increased within-litter variation. This is accompanied by impaired colostrum intake of piglets and poor performance. We aimed to investigate the total count of fecal lactobacilli and species diversity in growing pigs on two herds. Study pigs were categorized either small or large according to their birth weight. Sow colostrum quality and colostrum supply of piglets were determined. We hypothesized that the birth weight and growth performance of pigs are associated with fecal lactobacilli composition, which is influenced by colostrum. Small pigs had higher lactobacilli counts in both herds, but the difference was significant only for one herd (p = 0.01). Colostrum quality was numerically better in the herd that appeared also better managed in comparison to the other study herd. Colostrum intake tended to be significantly associated with the total lactobacilli count in the better-managed herd. In conclusion, herd-level factors clearly contribute to the microbiota of pigs, but birth weight also plays a potential role in the gastrointestinal tract lactobacilli dynamics. Our results revealed a potential long-term effect of colostrum, and therefore give a reason to investigate more thoroughly the associations between maternal immunity, pig microbiota, and performance. Abstract We studied the fecal lactobacilli count and species diversity of growing pigs along with immune parameters associated with intestinal lactobacilli. Thirty pigs categorized as small (S, n = 12) or large (L, n = 18) at birth were followed from birth to slaughter in two commercial herds, H1 and H2. Herds differed in terms of their general management. We determined sow colostrum quality, colostrum intake, piglet serum immunoglobulins, and pig growth. We took individual fecal samples from pigs in the weaning and finishing units. We studied lactobacilli count and identified their diversity with 16S PCR. Total lactobacilli count increased in H1 and decreased in H2 between samplings. Lactobacilli species diversity was higher in H1 in both fecal sampling points, whereas diversity decreased over time in both herds. We identified altogether seven lactobacilli species with a maximum of five (one to five) species in one herd. However, a relatively large proportion of lactobacilli remained unidentified with the used sequencing technique. Small pigs had higher lactobacilli counts in both herds but the difference was significant only in H2 (p = 0.01). Colostrum quality was numerically better in H1 than in H2, where colostrum intake tended to be associated with total lactobacilli count (p = 0.05).
Collapse
|