|
1
|
Vievermanns K, Dierikx TH, Oldenburger NJ, Jamaludin FS, Niemarkt HJ, de Meij TGJ. Effect of probiotic supplementation on the gut microbiota in very preterm infants: a systematic review. Arch Dis Child Fetal Neonatal Ed 2024; 110:57-67. [PMID: 38925919 DOI: 10.1136/archdischild-2023-326691] [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: 11/27/2023] [Accepted: 05/13/2024] [Indexed: 06/28/2024]
Abstract
OBJECTIVE There is increasing evidence that probiotic supplementation in very preterm infants decreases the risk of necrotising enterocolitis (NEC), sepsis and mortality. The underlying mechanisms, including effects on the gut microbiota, are largely unknown. We aimed to systematically review the available literature on the effects of probiotic supplementation in very preterm infants on gut microbiota development. DESIGN A systematic review in Medline, Embase, Cochrane Library, CINAHL and Web of Science. SETTING Neonatal intensive care unit. PATIENTS Premature infants. INTERVENTION Probiotic supplementation. MAIN OUTCOME MEASURES Gut microbiota. RESULTS A total of 1046 articles were screened, of which 29 were included. There was a large heterogeneity in study design, dose and type of probiotic strains, timepoints of sample collection and analysing techniques. Bifidobacteria and lactobacilli were the most used probiotic strains. The effects of probiotics on alpha diversity were conflicting; however, beta diversity was significantly different between probiotic-supplemented infants and controls in the vast majority of studies. In most studies, probiotic supplementation led to increased relative abundance of the supplemented strains and decreased abundance of genera such as Clostridium, Streptococcus, Klebsiella and Escherichia. CONCLUSIONS Probiotic supplementation to preterm infants seems to increase the relative abundance of the supplemented strains with a concurrent decrease of potentially pathogenic species. These probiotic-induced microbial alterations may contribute to the decreased risk of health complications such as NEC. Future trials, including omics technologies to analyse both microbiota composition and function linked to health outcomes, are warranted to identify the optimal mixture and dosing of probiotic strains. PROSPERO REGISTRATION NUMBER CRD42023385204.
Collapse
Affiliation(s)
- Kayleigh Vievermanns
- Pediatric Gastroenterology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
| | - Thomas H Dierikx
- Pediatric Gastroenterology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
- Microbiology, Maastricht UMC+, Maastricht, The Netherlands
| | | | - Faridi S Jamaludin
- Medical Library AMC, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
| | - Hendrik J Niemarkt
- Neonatology, Maxima Medisch Centrum locatie Veldhoven, Veldhoven, The Netherlands
- Electrical Engineering, TU Eindhoven, Eindhoven, The Netherlands
| | - Tim G J de Meij
- Pediatric Gastroenterology, Amsterdam UMC Locatie AMC, Amsterdam, The Netherlands
- Pediatric Gastroenterology, Emma children's hospital amsterdam, Amsterdam, The Netherlands
| |
Collapse
|
|
2
|
Srinivasjois R, Gebremedhin A, Silva D, Rao SC, Tessema GA, Pereira G. Probiotic Supplementation in the Neonatal Age Group and the Risk of Hospitalisation in the First Two Years: A Data Linkage Study from Western Australia. Nutrients 2024; 16:2094. [PMID: 38999842 PMCID: PMC11243646 DOI: 10.3390/nu16132094] [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: 05/30/2024] [Revised: 06/17/2024] [Accepted: 06/24/2024] [Indexed: 07/14/2024] Open
Abstract
BACKGROUND Probiotic supplementation in preterm neonates is standard practice in many centres across the globe. The impact of probiotic supplementation in the neonatal age group on the risk of hospitalisation in infancy has not been reported previously. METHODS Infants born < 32 + 6 weeks of gestation in Western Australia were eligible for inclusion. We conducted a retrospective cohort study comparing data from before probiotic supplementation (Epoch 1: 1 December 2008-30 November 2010, n = 1238) versus after (Epoch 2: 1 June 2012-30 May 2014, n = 1422) on the risks of respiratory- and gastrointestinal infection-related hospitalisation. A subgroup analysis of infants born < 28 weeks of gestation was analysed separately for similar outcomes. RESULTS Compared to Epoch 1, an 8% reduction in incidence of hospitalisation up to 2 years after birth was observed in Epoch 2 (adjusted incidence rate ratio (IRR) of 0.92; 95% confidence interval (CI); 0.87-0.98), adjusted for gestational age, smoking, socioeconomic status, and maternal age. The rate of hospitalisation for infants born < 28 weeks of gestation was comparable in epochs 1 and 2. CONCLUSION Infants exposed to probiotic supplementation in the neonatal period experience a reduced risk of hospitalisation in the first two years after discharge from the neonatal unit.
Collapse
Affiliation(s)
- Ravisha Srinivasjois
- Curtin School of Population Health, Curtin University, Perth, WA 6102, Australia; (A.G.); (G.A.T.); (G.P.)
- Department of Paediatrics and Neonatology, Joondalup Health Campus, Perth, WA 6027, Australia;
- School of Medicine, University of Western Australia, Perth, WA 6005, Australia;
| | - Amanuel Gebremedhin
- Curtin School of Population Health, Curtin University, Perth, WA 6102, Australia; (A.G.); (G.A.T.); (G.P.)
- EnAble Institute, Curtin University, Perth, WA 6102, Australia
| | - Desiree Silva
- Department of Paediatrics and Neonatology, Joondalup Health Campus, Perth, WA 6027, Australia;
- School of Medicine, University of Western Australia, Perth, WA 6005, Australia;
| | - Shripada C. Rao
- School of Medicine, University of Western Australia, Perth, WA 6005, Australia;
- Neonatal Directorate, Child and Adolescent Health Service, Perth Children’s Hospital, Perth, WA 6009, Australia
| | - Gizachew A. Tessema
- Curtin School of Population Health, Curtin University, Perth, WA 6102, Australia; (A.G.); (G.A.T.); (G.P.)
- EnAble Institute, Curtin University, Perth, WA 6102, Australia
| | - Gavin Pereira
- Curtin School of Population Health, Curtin University, Perth, WA 6102, Australia; (A.G.); (G.A.T.); (G.P.)
- EnAble Institute, Curtin University, Perth, WA 6102, Australia
| |
Collapse
|
|
3
|
TAKESHITA K, TAKEI H, TANAKA S, HISHIKI H, IIJIMA Y, OGATA H, FUJISHIRO K, TOMINAGA T, KONNO Y, IWASE Y, ENDO M, ISHIWADA N, OSONE Y, TAKEMURA R, HAMADA H, SHIMOJO N. Effect of multi-strain bifidobacteria supplementation on intestinal microbiota development in low birth weight neonates: a randomized controlled trial. BIOSCIENCE OF MICROBIOTA, FOOD AND HEALTH 2024; 43:352-358. [PMID: 39364130 PMCID: PMC11444860 DOI: 10.12938/bmfh.2023-093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Accepted: 05/21/2024] [Indexed: 10/05/2024]
Abstract
Single-strain Bifidobacterium species are commonly used as probiotics with low birth weight neonates. However, the effectiveness and safety of multi-strain Bifidobacterium supplementation are not well known. Thirty-six neonates weighing less than 2,000 g (558-1,943 g) at birth and admitted to a neonatal intensive care unit were randomly assigned to receive a single strain or triple strains of Bifidobacterium with lactulose enterally for 4 weeks from birth. The relative abundances of Staphylococcus and Bifidobacterium in the fecal microbiota at weeks 1, 2, and 4 were investigated. Based on the study results, no significant difference was detected between the two groups in the abundance of Staphylococcus; however, the triple-strain group had significantly high abundances of Bifidobacterium at weeks 2 and 4. The fecal microbiota in the triple-strain group had significantly lower alpha diversity (Bifidobacterium-enriching) after week 4 and was different from that in the single-strain group, which showed a higher abundance of Clostridium. No severe adverse events occurred in either group during the study period. Although no significant difference was detected between single- and multi-strain bifidobacteria supplementation in the colonization of Staphylococcus in the fecal microbiota of the neonates, multi-strain bifidobacteria supplementation contributed toward early enrichment of the microbiota with bifidobacteria and suppression of other pathogenic bacteria, such as Clostridium spp.
Collapse
Affiliation(s)
- Kenichi TAKESHITA
- Department of Pediatrics, Graduate School of Medicine, Chiba
University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
- Department of Pediatrics, Chiba Rosai Hospital, 2-16
Tatsumidaihigashi, Ichihara-shi, Chiba 290-0003, Japan
| | - Haruka TAKEI
- Department of Pediatrics, Graduate School of Medicine, Chiba
University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
| | - Saori TANAKA
- Department of Pediatrics, Graduate School of Medicine, Chiba
University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
| | - Haruka HISHIKI
- Department of Pediatrics, Graduate School of Medicine, Chiba
University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
| | - Yuta IIJIMA
- Department of Pediatrics, Graduate School of Medicine, Chiba
University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
- Perinatal Medical Center, Chiba University Hospital, 1-8-1
Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan
| | - Hitoshi OGATA
- Department of Pediatrics, Graduate School of Medicine, Chiba
University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
- Perinatal Medical Center, Chiba University Hospital, 1-8-1
Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan
| | - Kensuke FUJISHIRO
- Department of Pediatrics, Graduate School of Medicine, Chiba
University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
- Perinatal Medical Center, Chiba University Hospital, 1-8-1
Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan
| | - Takahiro TOMINAGA
- Department of Pediatrics, Graduate School of Medicine, Chiba
University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
- Perinatal Medical Center, Chiba University Hospital, 1-8-1
Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan
| | - Yuki KONNO
- Department of Pediatrics, Graduate School of Medicine, Chiba
University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
- Perinatal Medical Center, Chiba University Hospital, 1-8-1
Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan
| | - Yukiko IWASE
- Department of Pediatrics, Graduate School of Medicine, Chiba
University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
- Perinatal Medical Center, Chiba University Hospital, 1-8-1
Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan
| | - Mamiko ENDO
- Department of Pediatrics, Graduate School of Medicine, Chiba
University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
- Perinatal Medical Center, Chiba University Hospital, 1-8-1
Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan
| | - Naruhiko ISHIWADA
- Department of Infectious Diseases, Medical Mycology Research
Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8673, Japan
| | - Yoshiteru OSONE
- Department of Pediatrics, Graduate School of Medicine, Chiba
University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
- Perinatal Medical Center, Chiba University Hospital, 1-8-1
Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan
| | - Ryo TAKEMURA
- Clinical and Translational Research Center, Keio University
Hospital, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
| | - Hiromichi HAMADA
- Department of Pediatrics, Graduate School of Medicine, Chiba
University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
| | - Naoki SHIMOJO
- Center for Preventive Medical Sciences, Chiba University,
1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8670, Japan
| |
Collapse
|
|
4
|
Alba C, Carrera M, Álvarez-Calatayud G, Arroyo R, Fernández L, Rodríguez JM. Evaluation of Safety and Beneficial Health Effects of the Human-Milk Strain Bifidobacterium breve DSM32583: An Infant Pilot Trial. Nutrients 2024; 16:1134. [PMID: 38674825 PMCID: PMC11053739 DOI: 10.3390/nu16081134] [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: 03/15/2024] [Revised: 04/05/2024] [Accepted: 04/10/2024] [Indexed: 04/28/2024] Open
Abstract
Human milk promotes the growth of bifidobacteria in the infant gut. Adding bifidobacterial species to infant formula may contribute to increasing their presence in the gut of formula-fed infants. Therefore, the safety and anti-infectious effects of Bifidobacterium breve DSM32583, a breast milk isolate, were assessed in a pilot trial involving 3-month-old infants. The infants were randomly assigned to either the probiotic (PG) or the control (CG) groups. All the infants consumed the same formula, although it was supplemented with the strain (1 × 107 cfu/g of formula) in the PG. Overall, 160 infants (80 per group) finished the intervention. Infants in CG gained more weight compared to PG (p < 0.05), but the weights for age Z-scores at 6 months were within the normal distribution for this age group. The rates of infections affecting the gastrointestinal and respiratory tracts and antibiotic therapy were significantly lower in the PG. The bifidobacterial population and the level of short-chain fatty acids were higher (p < 0.05) in the fecal samples of PG infants. No adverse events related to formula consumption were observed. In conclusion, the administration of an infant formula with B. breve DSM32583 was safe and exerted potential beneficial effects on gut health.
Collapse
Affiliation(s)
- Claudio Alba
- Department of Nutrition and Food Science, Complutense University of Madrid, 28040 Madrid, Spain; (C.A.); (R.A.)
| | - Marta Carrera
- Centro de Atención Primaria Silvano, Comunidad de Madrid, 28043 Madrid, Spain;
| | | | - Rebeca Arroyo
- Department of Nutrition and Food Science, Complutense University of Madrid, 28040 Madrid, Spain; (C.A.); (R.A.)
| | - Leónides Fernández
- Department of Galenic Pharmacy and Food Technology, Complutense University of Madrid, 28040 Madrid, Spain;
| | - Juan M. Rodríguez
- Department of Nutrition and Food Science, Complutense University of Madrid, 28040 Madrid, Spain; (C.A.); (R.A.)
| |
Collapse
|
|
5
|
Kopczyńska J, Kowalczyk M. The potential of short-chain fatty acid epigenetic regulation in chronic low-grade inflammation and obesity. Front Immunol 2024; 15:1380476. [PMID: 38605957 PMCID: PMC11008232 DOI: 10.3389/fimmu.2024.1380476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 03/18/2024] [Indexed: 04/13/2024] Open
Abstract
Obesity and chronic low-grade inflammation, often occurring together, significantly contribute to severe metabolic and inflammatory conditions like type 2 diabetes (T2D), cardiovascular disease (CVD), and cancer. A key player is elevated levels of gut dysbiosis-associated lipopolysaccharide (LPS), which disrupts metabolic and immune signaling leading to metabolic endotoxemia, while short-chain fatty acids (SCFAs) beneficially regulate these processes during homeostasis. SCFAs not only safeguard the gut barrier but also exert metabolic and immunomodulatory effects via G protein-coupled receptor binding and epigenetic regulation. SCFAs are emerging as potential agents to counteract dysbiosis-induced epigenetic changes, specifically targeting metabolic and inflammatory genes through DNA methylation, histone acetylation, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). To assess whether SCFAs can effectively interrupt the detrimental cascade of obesity and inflammation, this review aims to provide a comprehensive overview of the current evidence for their clinical application. The review emphasizes factors influencing SCFA production, the intricate connections between metabolism, the immune system, and the gut microbiome, and the epigenetic mechanisms regulated by SCFAs that impact metabolism and the immune system.
Collapse
Affiliation(s)
- Julia Kopczyńska
- Laboratory of Lactic Acid Bacteria Biotechnology, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland
| | | |
Collapse
|
|
6
|
Batta VK, Rao SC, Patole SK. Bifidobacterium infantis as a probiotic in preterm infants: a systematic review and meta-analysis. Pediatr Res 2023; 94:1887-1905. [PMID: 37460707 PMCID: PMC10665187 DOI: 10.1038/s41390-023-02716-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Accepted: 06/08/2023] [Indexed: 11/24/2023]
Abstract
BACKGROUND Bifidobacterium infantis has special abilities to utilise human milk oligosaccharides. Hence we hypothesised that probiotic supplements containing B. infantis may confer greater benefits to preterm infants than probiotic supplements without B. infantis. METHODS A systematic review with meta-analysis was conducted according to standard guidelines. We selected RCTs evaluating probiotics compared to placebo or no treatment in preterm and/or low birth weight infants. Probiotic effects on Necrotizing Enterocolitis (NEC), Late Onset Sepsis (LOS) and Mortality were analysed separately for RCTs in which the supplemented probiotic product contained B. infantis and those that did not contain B. infantis. RESULTS 67 RCTs were included (n = 14,606), of which 16 used probiotics containing B. infantis (Subgroup A) and 51 RCTs did not (Subgroup B) Meta-analysis of all RCTs indicated that probiotics reduced the risk of NEC, LOS, and mortality. The subgroup meta-analysis demonstrated greater reduction in the incidence of NEC in subgroup A than subgroup B [(relative risk in subgroup A: 0.38; 95% CI, 0.27-0.55) versus (0.67; 95% CI, 0.55-0.81) in subgroup B; p value for subgroup difference: 0.01]. CONCLUSIONS These results provide indirect evidence that probiotic supplements that include B. infantis may be more beneficial for preterm infants. Well-designed RCTs are necessary to confirm these findings. IMPACT Evidence is emerging that beneficial effects of probiotics are species and strain specific. This systematic review analyses if B. infantis supplementation provides an advantage to preterm infants. This is the first systematic review evaluating the effects of probiotics containing B. infantis in preterm infants. The results of this systematic review provides indirect evidence that probiotics that include B. infantis may be more beneficial for preterm infants. These results will help in guiding future research and clinical practice for using B. infantis as a probiotic in preterm infants.
Collapse
Affiliation(s)
- Vamsi K Batta
- Neonatal Intensive Care Unit, Perth Children's Hospital, Perth, WA, Australia
- Neonatal Intensive Care Unit, King Edward Memorial Hospital, Perth, WA, Australia
| | - Shripada C Rao
- Neonatal Intensive Care Unit, Perth Children's Hospital, Perth, WA, Australia.
- School of Medicine, University of Western Australia, Perth, WA, Australia.
| | - Sanjay K Patole
- Neonatal Intensive Care Unit, King Edward Memorial Hospital, Perth, WA, Australia
- School of Medicine, University of Western Australia, Perth, WA, Australia
| |
Collapse
|
|
7
|
Zhou J, Yang M, Wang F, Liu S, Hei M, Jiang M. Assessment of food supplements for the prevention of necrotizing enterocolitis in preterm neonates: A systematic review and network meta-analysis. Comput Biol Med 2023; 167:107601. [PMID: 37924642 DOI: 10.1016/j.compbiomed.2023.107601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 09/14/2023] [Accepted: 10/17/2023] [Indexed: 11/06/2023]
Abstract
BACKGROUND The network meta-analysis (NMA) investigated the efficacy of six food supplements, namely glutamine, arginine, lactoferrin, prebiotics, synbiotics, and probiotics, in preventing necrotizing enterocolitis in premature infants. METHODS MEDLINE, Embase, and Cochrane Library were searched. Randomized controlled trials comparing different food supplements for premature infants were included. RESULTS Probiotics (OR, 0.47; 95% CrI, 0.33-0.63), arginine (OR, 0.38; 95% CrI, 0.14-0.98), glutamine (OR, 0.30; 95% CrI, 0.079-0.90), and synbiotics (OR, 0.13; 95% CrI, 0.037-0.37). were associated with a decreased incidence of NEC. Only probiotics (OR, 0.81; 95% CrI, 0.69-0.95) and lactoferrin (OR, 0.74; 95% CrI, 0.54-0.92) achieved lower risk of sepsis. Probiotics (OR, 0.58; 95% CrI, 0.40-0.79), prebiotics (OR, 0.23; 95% CrI, 0.043-0.86), and synbiotics (OR, 0.15; 95% CrI, 0.035-0.50) were associated with lower odds of mortality. Probiotics (MD, -2.3; 95% CrI: -3.7- -0.63) appeared to have earlier age of attainment of full feeding. CONCLUSIONS Based on this NMA, probiotics and synbiotics had the potential to be the top two preferable food supplements.
Collapse
Affiliation(s)
- Jingjing Zhou
- Department of Neonatology, Neonatal Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 Nanlishi Road, Xicheng District, Beijing, China
| | - Mengyang Yang
- Department of Neonatology, Neonatal Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 Nanlishi Road, Xicheng District, Beijing, China
| | - Fuming Wang
- Department of Neonatology, Kaifeng Children's Hospital, 87 Middle Section of Freedom Road, Kaifeng City, Henan Province, China
| | - Shiqi Liu
- Department of Neonatology, Neonatal Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 Nanlishi Road, Xicheng District, Beijing, China
| | - Mingyan Hei
- Department of Neonatology, Neonatal Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 Nanlishi Road, Xicheng District, Beijing, China
| | - Min Jiang
- Department of Neonatology, Neonatal Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, 56 Nanlishi Road, Xicheng District, Beijing, China.
| |
Collapse
|
|
8
|
Ma G, Shi Y, Meng L, Fan H, Tang X, Luo H, Wang D, Zhou J, Xiao X. Factors affecting the early establishment of neonatal intestinal flora and its intervention measures. Front Cell Infect Microbiol 2023; 13:1295111. [PMID: 38106467 PMCID: PMC10722192 DOI: 10.3389/fcimb.2023.1295111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Accepted: 11/17/2023] [Indexed: 12/19/2023] Open
Abstract
In recent years, it has become evident that early-life intestinal flora plays a pivotal role in determining human health. Consequently, it is imperative to explore the establishment of neonatal intestinal flora and its influencing factors. Early neonatal intestinal flora is influenced by a multitude of factors, including maternal and infant-related factors, as well as external environment. This review summarizes the colonization mechanism of intestinal flora in the early life of newborns and discussed their influence on the establishment of neonatal intestinal flora, taking into account factors such as delivery mode, gestational age and feeding mode. Additionally, this review delves into the natural or artificial reconstruction of intestinal flora colonization defects in infants born via cesarean section and premature infants, with the goal of establishing a theoretical foundation for preventing and treating issues related to neonatal intestinal flora colonization and associated diseases.
Collapse
Affiliation(s)
- Guangyu Ma
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Yuguo Shi
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Lulu Meng
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Haolong Fan
- National Key Laboratory of Science and Technology on Advanced Composites in Special Environments and Center for Composite Materials and Structures, Harbin Institute of Technology, Harbin, China
| | - Xiaomei Tang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Huijuan Luo
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Dongju Wang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Juan Zhou
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Xiaomin Xiao
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou, China
| |
Collapse
|
|
9
|
Heston SM, Lim CSE, Ong C, Chua MC, Kelly MS, Yeo KT. Strain-resolved metagenomic analysis of the gut as a reservoir for bloodstream infection pathogens among premature infants in Singapore. Gut Pathog 2023; 15:55. [PMID: 37974294 PMCID: PMC10652614 DOI: 10.1186/s13099-023-00583-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Accepted: 11/08/2023] [Indexed: 11/19/2023] Open
Abstract
BACKGROUND Gut dysbiosis contributes to the high risk of bloodstream infection (BSI) among premature infants. Most prior studies of the premature infant gut microbiota were conducted in Western countries and prior to development of current tools for strain-resolved analysis. METHODS We performed metagenomic sequencing of weekly fecal samples from 75 premature infants at a single hospital in Singapore. We evaluated associations between clinical factors and gut microbiota composition using PERMANOVA and mixed effects linear regression. We used inStrain to perform strain-level analyses evaluating for gut colonization by BSI-causing strains. RESULTS Median (interquartile range) gestation was 27 (25, 29) weeks, and 63% of infants were born via Cesarean section. Antibiotic exposures (PERMANOVA; R2 = 0.017, p = 0.001) and postnatal age (R2 = 0.015, p = 0.001) accounted for the largest amount of variability in gut microbiota composition. Increasing postnatal age was associated with higher relative abundances of several common pathogens (Enterococcus faecalis: p < 0.0001; Escherichia coli: p < 0.0001; Klebsiella aerogenes: p < 0.0001; Klebsiella pneumoniae: p < 0.0001). Antibiotic exposures were generally associated with lower relative abundances of both frequently beneficial bacteria (e.g., Bifidobacterium species) and common enteric pathogens (e.g., Enterobacter, Klebsiella species). We identified strains identical to the blood culture isolate in fecal samples from 12 of 16 (75%) infants who developed BSI, including all infections caused by typical enteric bacteria. CONCLUSIONS Antibiotic exposures were the dominant modifiable factor affecting gut microbiota composition in a large cohort of premature infants from South-East Asia. Strain-resolved analyses indicate that the gut is an important reservoir for organisms causing BSI among premature infants.
Collapse
Affiliation(s)
- Sarah M Heston
- Division of Pediatric Infectious Diseases, Duke University School of Medicine, Durham, NC, USA
| | - Charis Shu En Lim
- Department of Neonatology, KK Women's and Children's Hospital, Singapore, Singapore
| | - Chengsi Ong
- Department of Neonatology, KK Women's and Children's Hospital, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
- Department of Nutrition and Dietetics, KK Women's and Children's Hospital, Singapore, Singapore
| | - Mei Chien Chua
- Department of Neonatology, KK Women's and Children's Hospital, Singapore, Singapore
- Duke-NUS Medical School, Singapore, Singapore
| | - Matthew S Kelly
- Division of Pediatric Infectious Diseases, Duke University School of Medicine, Durham, NC, USA
| | - Kee Thai Yeo
- Department of Neonatology, KK Women's and Children's Hospital, Singapore, Singapore.
- Duke-NUS Medical School, Singapore, Singapore.
| |
Collapse
|
|
10
|
Rath CP, Athalye-Jape G, Nathan E, Doherty D, Rao S, Patole S. Benefits of routine probiotic supplementation in preterm infants. Acta Paediatr 2023; 112:2352-2358. [PMID: 37505925 DOI: 10.1111/apa.16924] [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: 04/01/2023] [Revised: 07/24/2023] [Accepted: 07/26/2023] [Indexed: 07/30/2023]
Abstract
AIM We introduced routine probiotic supplementation (RPS) of preterm infants in June 2012. We previously reported that RPS reduced the incidence of necrotising enterocolitis (NEC) and mortality in such infants. In this study, we assessed if the benefits of RPS were sustained for infants in the current era. METHOD We compared the outcomes of preterm infants in recent epoch 3 (RPS, 1st June 2014 to 31st December 2019) versus epoch 2 (RPS, 1st June 2012 to 31st May 2014) and epoch 1 (no RPS, 1st December 2008 to 30th November 2010). Multiple logistic and Cox regression models were used to compare the outcomes. RESULTS There were 645 infants in epoch 1, 712 in epoch 2 and 1715 in epoch 3. Age at full feeds was significantly lower in epoch 3 vs. 2 and epoch 3 vs. 1 in infants <28 weeks of gestation. NEC and late-onset sepsis (LOS) were significantly lower in epoch 3 vs. 1 in infants <28 weeks. LOS and age at full feeds were significantly lower in epoch 3 vs. 2 and epoch 3 vs. 1 in infants with gestation 28 to 32 weeks. CONCLUSION The benefits associated with RPS were sustained during epoch 3.
Collapse
Affiliation(s)
- C P Rath
- Neonatology Directorate, King Edward Memorial Hospital for Women, Subiaco, Western Australia, Australia
- School of Medicine, University of Western Australia, Crawley, Western Australia, Australia
| | - G Athalye-Jape
- Neonatology Directorate, King Edward Memorial Hospital for Women, Subiaco, Western Australia, Australia
- School of Medicine, University of Western Australia, Crawley, Western Australia, Australia
| | - E Nathan
- Biostatistics, Women and Infants Research Foundation, Subiaco, Western Australia, Australia
- Division of Obstetrics and Gynaecology, University of Western Australia, Crawley, Western Australia, Australia
| | - D Doherty
- Biostatistics, Women and Infants Research Foundation, Subiaco, Western Australia, Australia
- Division of Obstetrics and Gynaecology, University of Western Australia, Crawley, Western Australia, Australia
| | - S Rao
- School of Medicine, University of Western Australia, Crawley, Western Australia, Australia
- Neonatal Directorate, Perth Children's Hospital, Nedlands, Western Australia, Australia
| | - S Patole
- Neonatology Directorate, King Edward Memorial Hospital for Women, Subiaco, Western Australia, Australia
- School of Medicine, University of Western Australia, Crawley, Western Australia, Australia
| |
Collapse
|
|
11
|
Tsuji M, Tanaka N, Koike H, Sato Y, Shimoyama Y, Itoh A. Various Organ Damages in Rats with Fetal Growth Restriction and Their Slight Attenuation by Bifidobacterium breve Supplementation. Life (Basel) 2023; 13:2005. [PMID: 37895387 PMCID: PMC10607936 DOI: 10.3390/life13102005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Revised: 09/14/2023] [Accepted: 09/27/2023] [Indexed: 10/29/2023] Open
Abstract
Children with fetal growth restriction (FGR) and its resultant low birthweight (LBW) are at a higher risk of developing various health problems later in life, including renal diseases, metabolic syndrome, and sarcopenia. The mechanism through which LBW caused by intrauterine hypoperfusion leads to these health problems has not been properly investigated. Oral supplementation with probiotics is expected to reduce these risks in children. In the present study, rat pups born with FGR-LBW after mild intrauterine hypoperfusion were supplemented with either Bifidobacterium breve (B. breve) or a vehicle from postnatal day 1 (P1) to P21. Splanchnic organs and skeletal muscles were evaluated at six weeks of age. Compared with the sham group, the LBW-vehicle group presented significant changes as follows: overgrowth from infancy to childhood; lighter weight of the liver, kidneys, and gastrocnemius and plantaris muscles; reduced height of villi in the ileum; and increased depth of crypts in the jejunum. Some of these changes were milder in the LBW-B.breve group. In conclusion, this rat model could be useful for investigating the mechanisms of how FGR-LBW leads to future health problems and for developing interventions for these problems. Supplementation with B. breve in early life may modestly attenuate these problems.
Collapse
Affiliation(s)
- Masahiro Tsuji
- Department of Food and Nutrition, Kyoto Women’s University, Kyoto 605-8501, Japan
| | - Nao Tanaka
- Department of Food and Nutrition, Kyoto Women’s University, Kyoto 605-8501, Japan
| | - Hitomi Koike
- Department of Food and Nutrition, Kyoto Women’s University, Kyoto 605-8501, Japan
| | - Yoshiaki Sato
- Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya 466-8560, Japan;
| | - Yoshie Shimoyama
- Department of Pathology, Nagoya University Hospital, Nagoya 466-8560, Japan
| | - Ayaka Itoh
- Department of Food and Nutrition, Kyoto Women’s University, Kyoto 605-8501, Japan
| |
Collapse
|
|
12
|
Panchal H, Athalye-Jape G, Rao S, Patole S. Growth and neuro-developmental outcomes of probiotic supplemented preterm infants-a systematic review and meta-analysis. Eur J Clin Nutr 2023; 77:855-871. [PMID: 36788356 PMCID: PMC10473962 DOI: 10.1038/s41430-023-01270-2] [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: 04/13/2022] [Revised: 01/21/2023] [Accepted: 01/24/2023] [Indexed: 02/16/2023]
Abstract
Gut dysbiosis is associated with sepsis and necrotizing enterocolitis in preterm infants, which can adversely affect long-term growth and neurodevelopment. We aimed to synthesise evidence for the effect of probiotic supplementation on growth and neurodevelopmental outcomes in preterm infants. MEDLINE, EMBASE, EMCARE, Cochrane CENTRAL, and grey literature were searched in February 2022. Only randomized controlled trials (RCTs) were included. Meta-analysis was performed using random effects model. Effect sizes were expressed as standardized mean difference (SMD), mean difference (MD) or risk ratio (RR) and their corresponding 95% confidence intervals (CI). Risk of Bias (ROB) was assessed using the ROB-2 tool. Certainty of Evidence (CoE) was summarized using GRADE guidelines. Thirty RCTs (n = 4817) were included. Meta-analysis showed that probiotic supplementation was associated with better short-term weight gain [SMD 0.24 (95%CI 0.04, 0.44); 22 RCTs (n = 3721); p = 0.02; I2 = 88%; CoE: low]. However, length [SMD 0.12 (95%CI -0.13, 0.36); 7 RCTs, (n = 899); p = 0.35; I2 = 69%; CoE: low] and head circumference [SMD 0.09 (95%CI -0.15, 0.34); 8 RCTs (n = 1132); p = 0.46; I2 = 76%; CoE: low] were similar between the probiotic and placebo groups. Probiotic supplementation had no effect on neurodevelopmental impairment [RR 0.91 (95%CI 0.76, 1.08); 5 RCTs (n = 1556); p = 0.27; I2 = 0%; CoE: low]. Probiotic supplementation was associated with better short-term weight gain, but did not affect length, head circumference, long-term growth, and neurodevelopmental outcomes of preterm infants. Adequately powered RCTs are needed in this area. Prospero Registration: CRD42020064992.
Collapse
Affiliation(s)
- Harshad Panchal
- Neonatal Directorate, King Edward Memorial Hospital for Women, Perth, WA, Australia
| | - Gayatri Athalye-Jape
- Neonatal Directorate, King Edward Memorial Hospital for Women, Perth, WA, Australia.
- School of Medicine, University of Western Australia, Perth, WA, Australia.
| | - Shripada Rao
- School of Medicine, University of Western Australia, Perth, WA, Australia
- Neonatal Directorate, Perth Children's Hospital, Perth, WA, Australia
| | - Sanjay Patole
- Neonatal Directorate, King Edward Memorial Hospital for Women, Perth, WA, Australia
- School of Medicine, University of Western Australia, Perth, WA, Australia
| |
Collapse
|
|
13
|
Sharif S, Meader N, Oddie SJ, Rojas-Reyes MX, McGuire W. Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Cochrane Database Syst Rev 2023; 7:CD005496. [PMID: 37493095 PMCID: PMC10370900 DOI: 10.1002/14651858.cd005496.pub6] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/27/2023]
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 probiotics to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of NEC and associated mortality and morbidity in very preterm or VLBW infants. OBJECTIVES To determine the effect of supplemental probiotics on the risk of NEC and associated mortality and morbidity in very preterm or very low birth weight infants. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, the Maternity and Infant Care database, and CINAHL from inception 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 probiotics with placebo or no probiotics in very preterm infants (born before 32 weeks' gestation) and VLBW infants (weighing less than 1500 g at birth). DATA COLLECTION AND ANALYSIS Two review authors independently evaluated risk of bias of the trials, extracted data, and synthesised effect estimates using risk ratios (RRs), risk differences (RDs), and mean differences (MDs), with associated 95% confidence intervals (CIs). The primary outcomes were NEC and all-cause mortality; secondary outcome measures were late-onset invasive infection (more than 48 hours after birth), duration of hospitalisation from birth, and neurodevelopmental impairment. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS We included 60 trials with 11,156 infants. Most trials were small (median sample size 145 infants). The main potential sources of bias were unclear reporting of methods for concealing allocation and masking caregivers or investigators in about half of the trials. The formulation of the probiotics varied across trials. The most common preparations contained Bifidobacterium spp., Lactobacillus spp., Saccharomyces spp., andStreptococcus spp., alone or in combination. Very preterm or very low birth weight infants Probiotics may reduce the risk of NEC (RR 0.54, 95% CI 0.46 to 0.65; I² = 17%; 57 trials, 10,918 infants; low certainty). The number needed to treat for an additional beneficial outcome (NNTB) was 33 (95% CI 25 to 50). Probiotics probably reduce mortality slightly (RR 0.77, 95% CI 0.66 to 0.90; I² = 0%; 54 trials, 10,484 infants; moderate certainty); the NNTB was 50 (95% CI 50 to 100). Probiotics probably have little or no effect on the risk of late-onset invasive infection (RR 0.89, 95% CI 0.82 to 0.97; I² = 22%; 49 trials, 9876 infants; moderate certainty). Probiotics may have little or no effect on neurodevelopmental impairment (RR 1.03, 95% CI 0.84 to 1.26; I² = 0%; 5 trials, 1518 infants; low certainty). Extremely preterm or extremely low birth weight infants Few data were available for extremely preterm or extremely low birth weight (ELBW) infants. In this population, probiotics may have little or no effect on NEC (RR 0.92, 95% CI 0.69 to 1.22, I² = 0%; 10 trials, 1836 infants; low certainty), all-cause mortality (RR 0.92, 95% CI 0.72 to 1.18; I² = 0%; 7 trials, 1723 infants; low certainty), or late-onset invasive infection (RR 0.93, 95% CI 0.78 to 1.09; I² = 0%; 7 trials, 1533 infants; low certainty). No trials provided data for measures of neurodevelopmental impairment in extremely preterm or ELBW infants. AUTHORS' CONCLUSIONS Given the low to moderate certainty of evidence for the effects of probiotic supplements on the risk of NEC and associated morbidity and mortality for very preterm or VLBW infants, and particularly for extremely preterm or ELBW infants, there is a need for further large, high-quality trials to provide evidence of sufficient validity and applicability to inform policy and practice.
Collapse
Key Words
- female
- humans
- infant
- infant, newborn
- enterocolitis, necrotizing
- enterocolitis, necrotizing/epidemiology
- fetal growth retardation
- infant, extremely premature
- infant, premature, diseases
- infant, premature, diseases/etiology
- infant, premature, diseases/prevention & control
- infant, very low birth weight
- probiotics
Collapse
Affiliation(s)
- Sahar Sharif
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Nicholas Meader
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Sam J Oddie
- Centre for Reviews and Dissemination, University of York, York, UK
- Bradford Neonatology, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
| | - Maria X Rojas-Reyes
- Institut d'Recerca Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
- Evaluation Unit of the Canary Islands Health Service (SESCS), Tenerife, Spain
| | - William McGuire
- Centre for Reviews and Dissemination, University of York, York, UK
| |
Collapse
|
|
14
|
Wang H, Meng X, Xing S, Guo B, Chen Y, Pan YQ. Probiotics to prevent necrotizing enterocolitis and reduce mortality in neonates: A meta-analysis. Medicine (Baltimore) 2023; 102:e32932. [PMID: 36827026 PMCID: PMC11309691 DOI: 10.1097/md.0000000000032932] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 01/21/2023] [Accepted: 01/23/2023] [Indexed: 02/25/2023] Open
Abstract
BACKGROUND Probiotics are gradually being used as a supplementation to prevent necrotizing enterocolitis (NEC) and reduce mortality in neonates. We performed an updated meta-analysis to systematically evaluate the efficacy and safety of prophylactic probiotic supplementation for preventing NEC. METHODS The databases including PubMed, Embase, Scopus, Web of Science, and China National Knowledge Infrastructure were used to search the relevant articles. The latest retrieval date was up to December 2021. The meta-analysis was performed using Stata version 10.0. Finally, a total of 70 studies containing 8319 cases and 9283 controls were included. The strength of the association between the supplementation of probiotics and NEC was measured by risk ratios (RRs) with 95% confidence intervals (CIs). Pooled effect sizes across studies were performed by a random effect model. RESULTS The results showed that the probiotics could significantly reduce the incidence of NEC (stage II or more) (RR = 0.436, 95% CI = 0.357-0.531, P < .001), the overall mortality (RR = 0.651, 95% CI = 0.506-0.836, P < .001), and NEC-related mortality (RR = 0.639, 95% CI = 0.423-0.966, P = .034). Due to the lack of sufficient sample size, we did not perform the subgroup analysis by types of probiotic strain. CONCLUSION This meta-analysis indicates that the use of probiotics can effectively reduce the occurrence of NEC and mortality in neonates.
Collapse
Affiliation(s)
- Hongbo Wang
- Department of Anatomy, Shenyang Medical College, Shenyang, China
| | - Xinyao Meng
- Department of Anatomy, Shenyang Medical College, Shenyang, China
| | - Shihan Xing
- Department of Anatomy, Shenyang Medical College, Shenyang, China
| | - Baotong Guo
- Department of Anatomy, Shenyang Medical College, Shenyang, China
| | - Yuhan Chen
- Department of Anatomy, Shenyang Medical College, Shenyang, China
| | - Yu-Qing Pan
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, PR China
| |
Collapse
|
|
15
|
Jankiewicz M, Łukasik J, Kotowska M, Kołodziej M, Szajewska H. Strain-Specificity of Probiotics in Pediatrics: A Rapid Review of the Clinical Evidence. J Pediatr Gastroenterol Nutr 2023; 76:227-231. [PMID: 36563089 DOI: 10.1097/mpg.0000000000003675] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE The dogma of probiotic strain-specificity is widely accepted. However, only the genus- and species-specific effects of probiotics are supported by evidence from clinical trials. The aim of this rapid review was to assess clinical evidence supporting the claim that the efficacy of probiotics in the pediatric population is strain-specific. METHODS The Cochrane Library, MEDLINE, and EMBASE databases were searched (up to August 2022) for randomized controlled trials (RCTs) conducted in children aged 0-18 years evaluating the effects of prophylactic or therapeutic administration of probiotics (well-characterized at the strain level) for conditions such as antibiotic-associated diarrhea, acute diarrhea, necrotizing enterocolitis, respiratory tract infections, Helicobacter pylori infection, and atopic dermatitis. To allow evaluation of strain-specificity, a trial could only be included in the review if at least one additional RCT assessed the effect of a different strain of the same species against the same comparator. RCTs without proper strain-level data were excluded. In the absence of identifying head-to-head strain versus strain RCTs, indirect comparisons were made between interventions. RESULTS Twenty-three RCTs were eligible for inclusion. Out of the 11 performed comparisons, with 1 exception (two Lacticaseibacillus paracasei strains in reducing atopic dermatitis symptoms), no significant differences between the clinical effects of different strains of the same probiotic species were found. CONCLUSIONS Head-to-head comparison is an optimal study design to compare probiotic strains, but such comparisons are lacking. Based on indirect comparisons, this rapid review demonstrates insufficient clinical evidence to support or refute the claim that probiotic effects in children are strain-specific.
Collapse
Affiliation(s)
- Mateusz Jankiewicz
- From the Department of Paediatrics, The Medical University of Warsaw, Warszawa, Poland
| | | | | | | | | |
Collapse
|
|
16
|
Sadeghpour Heravi F, Hu H. Bifidobacterium: Host-Microbiome Interaction and Mechanism of Action in Preventing Common Gut-Microbiota-Associated Complications in Preterm Infants: A Narrative Review. Nutrients 2023; 15:709. [PMID: 36771414 PMCID: PMC9919561 DOI: 10.3390/nu15030709] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 01/23/2023] [Accepted: 01/27/2023] [Indexed: 01/31/2023] Open
Abstract
The development and health of infants are intertwined with the protective and regulatory functions of different microorganisms in the gut known as the gut microbiota. Preterm infants born with an imbalanced gut microbiota are at substantial risk of several diseases including inflammatory intestinal diseases, necrotizing enterocolitis, late-onset sepsis, neurodevelopmental disorders, and allergies which can potentially persist throughout adulthood. In this review, we have evaluated the role of Bifidobacterium as commonly used probiotics in the development of gut microbiota and prevention of common diseases in preterm infants which is not fully understood yet. The application of Bifidobacterium as a therapeutical approach in the re-programming of the gut microbiota in preterm infants, the mechanisms of host-microbiome interaction, and the mechanism of action of this bacterium have also been investigated, aiming to provide new insights and opportunities in microbiome-targeted interventions in personalized medicine.
Collapse
Affiliation(s)
| | - Honghua Hu
- Macquarie Medical School, Macquarie University, Sydney, NSW 2109, Australia
- Innovation Center of Translational Pharmacy, Jinhua Institute of Zhejiang University, Jinhua 321016, China
| |
Collapse
|
|
17
|
Zhou KZ, Wu K, Deng LX, Hu M, Luo YX, Zhang LY. Probiotics to prevent necrotizing enterocolitis in very low birth weight infants: A network meta-analysis. Front Pediatr 2023; 11:1095368. [PMID: 36950176 PMCID: PMC10025406 DOI: 10.3389/fped.2023.1095368] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 02/17/2023] [Indexed: 03/24/2023] Open
Abstract
Objective This study aims to review the evidence for the optimal regimen of probiotics for the prevention of necrotizing enterocolitis (NEC) in very low birth weight infants. Design Through searching PubMed, EMBASE, Cochrane Library, and Web of Science till September 30, 2022, only randomized controlled trials were included to evaluate the optimal regimen of probiotics for the prevention of NEC in very low birth weight infants. The methodological quality of the included studies was assessed by the Cochrane risk of bias assessment tool (RoB 2), and the collected data were analyzed accordingly using Stata software. Results Twenty-seven RCTs were included, and the total sample size used in the study was 529. The results of the network meta-analysis showed that Bovine lactoferrin + Lactobacillus rhamnosus GG (RR 0.03; 95% CI 0.00-0.35), Lactobacillus rhamnosus + Lactobacillus plantarum + Lactobacillus casei + Bifidobacterium lactis (RR 0.06; 95% CI 0.00-0.70), Bifidobacterium lactis + inulin (RR 0.16; 95% CI 0.03-0.91) were superior to the control group (Bifidobacterium lactis + Bifidobacterium longum) in reducing the incidence of NEC. The reduction in the incidence of NEC were as follows: Bovine lactoferrin + Lactobacillus rhamnosus GG (SUCRA 95.7%) > Lactobacillus rhamnosus + Lactobacillus plantarum + Lactobacillus casei + Bifidobacterium lactis (SUCRA 89.4%) > Bifidobacterium lactis + inulin (SUCRA 77.8%). Conclusions This network meta-analysis suggests that Lactobacillus rhamnosus GG combined with bovine lactoferrin maybe the most recommended regimen for the prevention of NEC in very low birth weight infants.
Collapse
|
|
18
|
Rao S, Esvaran M, Chen L, Kok C, Keil AD, Gollow I, Simmer K, Wemheuer B, Conway P, Patole S. Probiotic supplementation for neonates with congenital gastrointestinal surgical conditions: guidelines for future research. Pediatr Res 2023; 93:49-55. [PMID: 35505080 PMCID: PMC9876795 DOI: 10.1038/s41390-022-02087-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2022] [Revised: 03/31/2022] [Accepted: 04/10/2022] [Indexed: 01/29/2023]
Abstract
Our pilot RCT found that probiotic supplementation with the three-strain bifidobacterial product (B. breve M-16V, B. longum subsp. infantis M-63 and B. longum subsp. longum BB536) attenuates gut dysbiosis, increases stool short-chain fatty acid (SCFA) levels and improves the growth of head circumference in neonates with congenital gastrointestinal surgical conditions (CGISC). In this article, we have provided guidelines for designing future multicentre RCTs based on the experience gained from our pilot RCT. The recommendations include advice about sample size, potential confounders, outcomes of interest, probiotic strain selection, storage, dose, duration and microbial quality assurance, collection of stool samples, storage and analysis and reporting. Following these guidelines will increase the validity of future RCTs in this area and hence confidence in their results. IMPACT: Probiotic supplementation attenuates gut dysbiosis, increases stool short-chain fatty acid (SCFA) levels and improves the growth of head circumference in neonates with congenital gastrointestinal surgical conditions. The current review provides evidence-based guidelines to conduct adequately powered RCTs in this field.
Collapse
Affiliation(s)
- Shripada Rao
- Neonatal Intensive Care Unit, Perth Children's Hospital, Perth, WA, Australia. .,Neonatal Intensive Care Unit, King Edward Memorial Hospital for Women, Perth, WA, Australia. .,School of Medicine, University of Western Australia, Crawley, WA, Australia.
| | - Meera Esvaran
- grid.1005.40000 0004 4902 0432Centre for Marine Science and Innovation at the University of New South Wales (UNSW), Sydney, NSW Australia
| | - Liwei Chen
- grid.59025.3b0000 0001 2224 0361School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore
| | - Chooi Kok
- grid.410667.20000 0004 0625 8600Neonatal Intensive Care Unit, Perth Children’s Hospital, Perth, WA Australia ,grid.415259.e0000 0004 0625 8678Neonatal Intensive Care Unit, King Edward Memorial Hospital for Women, Perth, WA Australia
| | - Anthony D. Keil
- grid.2824.c0000 0004 0589 6117Department of Microbiology, PathWest Laboratory Medicine, Perth, WA Australia
| | - Ian Gollow
- grid.410667.20000 0004 0625 8600Department of Paediatric Surgery, Perth Children’s Hospital, Perth, WA Australia
| | - Karen Simmer
- grid.410667.20000 0004 0625 8600Neonatal Intensive Care Unit, Perth Children’s Hospital, Perth, WA Australia ,grid.415259.e0000 0004 0625 8678Neonatal Intensive Care Unit, King Edward Memorial Hospital for Women, Perth, WA Australia ,grid.1012.20000 0004 1936 7910School of Medicine, University of Western Australia, Crawley, WA Australia
| | - Bernd Wemheuer
- grid.1005.40000 0004 4902 0432Centre for Marine Science and Innovation at the University of New South Wales (UNSW), Sydney, NSW Australia ,grid.7450.60000 0001 2364 4210Department of Genomic and Applied Microbiology, University of Göttingen, Göttingen, Germany
| | - Patricia Conway
- grid.1005.40000 0004 4902 0432Centre for Marine Science and Innovation at the University of New South Wales (UNSW), Sydney, NSW Australia ,grid.59025.3b0000 0001 2224 0361School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore
| | - Sanjay Patole
- grid.410667.20000 0004 0625 8600Neonatal Intensive Care Unit, Perth Children’s Hospital, Perth, WA Australia ,grid.415259.e0000 0004 0625 8678Neonatal Intensive Care Unit, King Edward Memorial Hospital for Women, Perth, WA Australia ,grid.1012.20000 0004 1936 7910School of Medicine, University of Western Australia, Crawley, WA Australia
| |
Collapse
|
|
19
|
Prado C, Abatti MR, Michels M, Córneo E, Cucker L, Borges H, Dias R, Rocha LB, Dal-Pizzol F, Ritter C. Comparative effects of fresh and sterile fecal microbiota transplantation in an experimental animal model of necrotizing enterocolitis. J Pediatr Surg 2022; 57:183-191. [PMID: 35058059 DOI: 10.1016/j.jpedsurg.2021.12.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 12/01/2021] [Accepted: 12/08/2021] [Indexed: 12/27/2022]
Abstract
INTRODUCTION Necrotizing Enterocolitis (NEC) is a serious intestinal disease that affects premature neonates, causing high mortality, despite the technological development in neonatal intensive care, with antibiotics, parenteral nutrition, surgery, and advanced life support. The correction of dysbiosis with fecal microbiome transplantation (FMT) has shown beneficial effects in experimental models of the disease. The different forms of administration and conservation of FMT and mixed results depending on several factors lead to questions about the mechanism of action of FMT. This study aimed to compare the effectiveness of fresh, sterile FMT and probiotic treatment under parameters of inflammation, oxidative stress, and tissue damage in a neonatal model of NEC. METHODS One-day-old Wistar rats were used to induce NEC model. Animals were divided in five groups: Control + saline; NEC + saline; NEC + fresh FMT; NEC + sterile FMT and NEC+ probiotics. Parameters of inflammatory response and oxidative damage were measured in the gut, brain, and serum. It was also determined gut histopathological alterations. RESULTS Proinflammatory cytokines were increased in the NEC group, and IL-10 levels decreased in the gut, brain, and serum. Fresh and sterile FMT decreased inflammation when compared to the use of probiotics. Oxidative and histological damage to the intestine was apparent in the NEC group, and both FMT treatments had a protective effect. CONCLUSION Fresh and sterile FMT effectively reduced the inflammatory response, oxidative damage, and histological alterations in the gut and brain compared to an experimental NEC model.
Collapse
Affiliation(s)
- Christian Prado
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
| | - Mariane Rocha Abatti
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
| | - Monique Michels
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
| | - Emily Córneo
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil.
| | - Luana Cucker
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
| | - Heloisa Borges
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
| | - Rodrigo Dias
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
| | - Luana Bezerra Rocha
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
| | - Felipe Dal-Pizzol
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
| | - Cristiane Ritter
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, 88806-000, Brazil
| |
Collapse
|
|
20
|
Zhang H, Zhang Z, Liao Y, Zhang W, Tang D. The Complex Link and Disease Between the Gut Microbiome and the Immune System in Infants. Front Cell Infect Microbiol 2022; 12:924119. [PMID: 35782111 PMCID: PMC9241338 DOI: 10.3389/fcimb.2022.924119] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Accepted: 05/23/2022] [Indexed: 11/13/2022] Open
Abstract
The human gut microbiome is important for human health. The development of stable microbial communities in the gastrointestinal tract is closely related to the early growth and development of host immunity. After the birth of a baby, immune cells and the gut microbiome mature in parallel to adapt to the complex gut environment. The gut microbiome is closely linked to the immune system and influences each other. This interaction is associated with various diseases in infants and young children, such as asthma, food allergies, necrotizing colitis, obesity, and inflammatory bowel disease. Thus, the composition of the infant gut microbiome can predict the risk of disease development and progression. At the same time, the composition of the infant gut microbiome can be regulated in many ways and can be used to prevent and treat disease in infants by modulating the composition of the infant gut microbiome. The most important impacts on infant gut microbiota are maternal, including food delivery and feeding. The differences in the gut microbiota of infants reflect the maternal gut microbiota, which in turn reflects the gut microbiota of a given population, which is clinically significant.
Collapse
Affiliation(s)
- Huan Zhang
- Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Zhilin Zhang
- Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Yiqun Liao
- Department of General Surgery, Institute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, China
| | - Wenjie Zhang
- Clinical Medical College, Yangzhou University, Yangzhou, China
| | - Dong Tang
- Department of General Surgery, Institute of General Surgery, Clinical Medical College, Yangzhou University, Northern Jiangsu People's Hospital, Yangzhou, China
| |
Collapse
|
|
21
|
Kulkarni T, Majarikar S, Deshmukh M, Ananthan A, Balasubramanian H, Keil A, Patole S. Probiotic sepsis in preterm neonates-a systematic review. Eur J Pediatr 2022; 181:2249-2262. [PMID: 35348825 DOI: 10.1007/s00431-022-04452-5] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Revised: 02/22/2022] [Accepted: 03/17/2022] [Indexed: 02/05/2023]
Abstract
UNLABELLED Sepsis due to the administered probiotic strain/s is a barrier against adoption of prophylactic probiotic supplementation in preterm infants to reduce the risk of necrotising enterocolitis (NEC ≥ Stage II), all-cause mortality, late-onset sepsis, and feeding intolerance. We aimed to conduct a systematic review for reports of probiotic sepsis in preterm infants (gestation < 37 weeks). Databases including PubMed, Embase, Emcare, Cochrane Central library, and Google Scholar were searched in August 2021 and updated in Jan 2022. Probiotic sepsis was defined as positive blood/CSF culture isolating administered probiotic strain with symptoms suggestive of infection. Data collection included birth weight, gestation, comorbidities (e.g. gut surgery, NEC), presence of central venous catheters, treatment, and outcome. Literature search revealed 1569 studies. A total of 16 reports [randomised control trial (RCT): none; non-RCT: 1; case series: 8; case report: 7] involving 32 preterm infants with probiotic sepsis were included after exclusions for various reasons. Majority of the cases were born < 32 weeks' gestation. Bifidobacterium (N = 19) was the most commonly isolated organism followed by Lactobacillus (N = 10), and Saccharomyces (N = 3). A total of 25/32 cases were confirmed to be due to the administered probiotic strain on full genomic analysis. Two studies reported one neonatal death each. Twelve neonates had comorbidities. Majority were treated with antibiotics (29/32) whereas others (3/32) required antifungal treatment. CONCLUSION Probiotics sepsis is relatively an uncommon event in preterm infants. Majority of the cases recovered after antibiotic or antifungal treatment. The importance of optimal surveillance and treatment of probiotic sepsis and research towards alternatives to probiotics (e.g. postbiotics) is emphasised. WHAT IS KNOWN • Probiotics have been shown to reduce necrotising enterocolitis, late-onset sepsis, all-cause mortality, and time to reach full enteral feeds in preterm infants. • Despite the evidence, use of probiotics is not universal due to concerns regarding probiotic-associated sepsis in preterm infants. WHAT IS NEW • This comprehensive systematic review showed that probiotic sepsis is a relatively rare phenomenon in preterm infants. • All except one case where the diagnosis was uncertain recovered after antimicrobial therapy.
Collapse
Affiliation(s)
- Tithi Kulkarni
- Department of Neonatal Paediatrics, King Edward Memorial Hospital, Perth, WA, Australia
| | - Swati Majarikar
- Department of Neonatology, Fiona Stanley Hospital, 11 Robin Warren Drive, Perth, WA, 6150, Australia
| | - Mangesh Deshmukh
- Department of Neonatology, Fiona Stanley Hospital, 11 Robin Warren Drive, Perth, WA, 6150, Australia.
- Department of Neonatology, St. John of God Hospital Subiaco, Perth, WA, Australia.
| | - Anitha Ananthan
- Department of Neonatology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
| | | | - Anthony Keil
- PathWest Laboratory Medicine Western Australia, Perth, WA, Australia
- King Edward Memorial Hospital, Perth, WA, Australia
| | - Sanjay Patole
- Department of Neonatal Paediatrics, King Edward Memorial Hospital, Perth, WA, Australia
- School of Medicine, University of Western Australia, Perth, WA, Australia
| |
Collapse
|
|
22
|
Athalye-Jape G, Esvaran M, Patole S, Simmer K, Nathan E, Doherty D, Keil A, Rao S, Chen L, Chandrasekaran L, Kok C, Schuster S, Conway P. Effect of single versus multistrain probiotic in extremely preterm infants: a randomised trial. BMJ Open Gastroenterol 2022; 9:bmjgast-2021-000811. [PMID: 35185013 PMCID: PMC8860036 DOI: 10.1136/bmjgast-2021-000811] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 01/12/2022] [Indexed: 11/03/2022] Open
Abstract
OBJECTIVE Evidence indicates that multistrain probiotics benefit preterm infants more than single-strain (SS) probiotics. We assessed the effects of SS versus triple-strain (TS) probiotic supplementation (PS) in extremely preterm (EP) infants. DESIGN EP infants (gestational age (GA) <28 weeks) were randomly allocated to TS or SS probiotic, assuring blinding. Reference (REF) group was EP infants in the placebo arm of our previous probiotic trial. PS was commenced with feeds and continued until 37 weeks' corrected GA. Primary outcome was time to full feed (TFF: 150 mL/kg/day). Secondary outcomes included short-chain fatty acids and faecal microbiota collected at T1 (first week) and T2 (after 3 weeks of PS) using 16S ribosomal RNA gene sequencing. RESULTS 173 EP (SS: 86, TS: 87) neonates with similar GA and birth weight (BW) were randomised. Median TFF was comparable (11 (IQR 8-16) vs 10 (IQR 8-16) days, p=0.92). Faecal propionate (SS, p<0.001, and TS, p=0.0009) and butyrate levels (TS, p=0.029) were significantly raised in T2 versus T1 samples. Secondary clinical outcomes were comparable. At T2, alpha diversity was comparable (p>0.05) between groups, whereas beta-diversity analysis revealed significant differences between PS and REF groups (both p=0.001). Actinobacteria were higher (both p<0.01), and Proteobacteria, Firmicutes and Bacteroidetes were lower in PS versus REF. Gammaproteobacteria, Clostridia and Negativicutes were lower in both PS versus REF. CONCLUSION TFF in EP infants was similar between SS and TS probiotics. Both probiotics were effective in reducing dysbiosis (higher bifidobacteria and lower Gammaproteobacteria). Long-term significance of increased propionate and butyrate needs further studies. TRIAL REGISTRATION NUMBER ACTRN 12615000940572.
Collapse
Affiliation(s)
- Gayatri Athalye-Jape
- Neonatology directorate, King Edward Memorial Hospital for Women Perth, Subiaco, Western Australia, Australia
| | - Meera Esvaran
- Faculty of Science, University of New South Wales, Sydney, New South Wales, Australia
| | - Sanjay Patole
- Neonatal Clinical Care Unit, King Edward Memorial Hospital, Subiaco, Western Australia, Australia
| | - Karen Simmer
- Neonatal Clinical Care Unit, King Edward Memorial Hospital, Subiaco, Western Australia, Australia
| | - Elizabeth Nathan
- Biostatistics, Women and Infants Research Foundation Western Australia, Subiaco, Western Australia, Australia
| | - Dorota Doherty
- Biostatistics, Women and Infants Research Foundation Western Australia, Subiaco, Western Australia, Australia
| | - Anthony Keil
- Microbiology, PathWest Laboratory Medicine Western Australia, Nedlands, Western Australia, Australia
| | - Shripada Rao
- Neonatal Clinical Care Unit, Perth Children's Hospital, Nedlands, Western Australia, Australia
| | - Liwei Chen
- Genomics and Bioinformatics, Nanyang Technological University, Singapore
| | | | - Chooi Kok
- Neonatal Clinical Care Unit, King Edward Memorial Hospital, Subiaco, Western Australia, Australia
| | - Stephan Schuster
- Genomics and Bioinformatics, Nanyang Technological University, Singapore
| | - Patricia Conway
- Genomics and Bioinformatics, Nanyang Technological University, Singapore
| |
Collapse
|
|
23
|
Zhang W, Wang S, Xing Y, Wang H, Fu B, Long M, Cao J. Clinical efficacy of probiotics on feeding intolerance in preterm infants: a systematic review and meta-analysis. Transl Pediatr 2022; 11:229-238. [PMID: 35282030 PMCID: PMC8905106 DOI: 10.21037/tp-21-624] [Citation(s) in RCA: 7] [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: 12/14/2021] [Accepted: 01/20/2022] [Indexed: 11/15/2022] Open
Abstract
BACKGROUND The physiological organ system of premature infants is still very immature, so it is easy to result feeding intolerance. Therefore, effective probiotic supplementation plays a very important role and clinical research significance in promoting the growth and development of preterm infants, improving the quality of life and improving the occurrence of feeding intolerance. To explore the clinical effect of probiotics on feeding intolerance (FI) in preterm infants by meta-analysis. METHODS The PubMed, Web of Science, EMBASE and MEDLINE literature databases were searched for relevant literature. The literature related to the clinical effect of probiotics on FI in preterm infants was published from January 2002 to January 2021. RevMan 5.3 was used to calculate the reinforcement mean difference (MD) and evaluate the publication bias. RESULTS Nine articles were included, involving a total of 1,244 preterm infants with FI. Through the sensitivity analysis of each excluded study, the results showed no significant differences. Compared with patients in the control group, the probiotics group had significant improvements (P<0.1) in the total intestinal feeding time (MD =-2.54, 95% CI: -3.57, -1.52, P<0.00001), weight gain (MD =23.81, 95% CI: 19.75, 27.81, P<0.00001), maximum enteral feeding (MD =6.41, 95% CI: 1.94, 10.88, P=0.005), hospital stay (MD =-5.18, 95% CI: -5.63, -4.74, P<0.00001), incidence of FI [odds rate (OR) =0.38, 95% CI: 0.27, 0.55, P<0.00001] and improvement in the gastrointestinal tract (OR =2.34, 95% CI: 1.07, 5.14, P=0.03). DISCUSSION Our study shows that the use of probiotics can promote the early growth of preterm infants and effectively improve the occurrence of FI in preterm infants.
Collapse
Affiliation(s)
- Wei Zhang
- Department of Neonatology, Hainan Women and Children's Medical Center, Haikou, China
| | - Shiqun Wang
- Department of Pediatrics, Qionghai Hospital of Traditional Chinese Medicine, Qionghai, China
| | - Yu Xing
- Department of Pediatrics, Hainan Modern Women and Children's Hospital, Haikou, China
| | - Hongyi Wang
- Department of Pediatrics, Hainan Modern Women and Children's Hospital, Haikou, China
| | - Binsha Fu
- Department of Pediatrics, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, China
| | - Mingjia Long
- Department of Pediatrics, Qionghai Hospital of Traditional Chinese Medicine, Qionghai, China
| | - Juan Cao
- Department of Pediatrics, Hainan Modern Women and Children's Hospital, Haikou, China
| |
Collapse
|
|
24
|
Risk factors for hyperglycemia in extremely low birth weight infants during the first 14 days. Pediatr Neonatol 2022; 63:13-18. [PMID: 34330686 DOI: 10.1016/j.pedneo.2021.07.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/17/2021] [Accepted: 07/05/2021] [Indexed: 11/20/2022] Open
Abstract
BACKGROUND There are limited data regarding the risk factors for hyperglycemia in extremely low birth weight infants (ELBWIs). The aim of this observational study was to investigate the incidence of hyperglycemia among ELBWIs during the first 14 days of life and identify independent risk factors for hyperglycemia development. METHODS We retrospectively evaluated 55 ELBWIs (32 male infants) between January 2015 and March 2020. Hyperglycemia was diagnosed when the glucose level was ≥180 mg/dL. Demographic and clinical data were extracted from the patients' medical records. The risk factors associated with the onset of hyperglycemia were identified by Cox proportional hazards regression analysis with variables that had previously been identified as risk factors for hyperglycemia. RESULTS Hyperglycemia developed in 23 patients (41.8%) within the first 14 days of life. Gestational age, chorioamnionitis, postnatal intravenous glucocorticoids, and probiotic type were included in the analysis. The results indicated that hyperglycemia was significantly associated with gestational age (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.48-0.87; P = 0.004). Further, Bifidobacterium breve (B. breve M-16V) use was related to hyperglycemia in ELBWIs (HR, 2.95; 95% CI, 1.10-7.87; P = 0.031). CONCLUSION Hyperglycemia was strongly associated with lower gestational age and B. breve M-16V use in our study population. Although probiotic supplementation may be beneficial for preterm infants to reduce the incidence of necrotizing enterocolitis, the dextrin used as an excipient in B. breve M-16V may lead to an undesirable carbohydrate load in ELBWIs.
Collapse
|
|
25
|
Itoh A, Tanaka N, Fukunaga S, Nakano-Doi A, Matsuyama T, Nakagomi T, Tsuji M. Bifidobacterium breve during infancy attenuates mobility in low birthweight rats. Pediatr Int 2022; 64:e15209. [PMID: 35938576 DOI: 10.1111/ped.15209] [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] [Received: 12/28/2021] [Revised: 03/25/2022] [Accepted: 04/05/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND Children with low birthweight (LBW) have a higher risk for developing attention-deficit/hyperactivity disorder, for which no prophylactic measure exists. The gut microbiota in infants with LBW is different from that in infants with normal birthweight and is associated with attention-deficit/hyperactivity disorder. Oral supplementation with Bifidobacterium has several health benefits, such as suppressing inflammation. METHODS We examined the effect of gavage supplementation with Bifidobacterium breve M-16V from postnatal days 1-21 in a rat model of intrauterine hypoperfusion. RESULTS The open-field test at 5 weeks of age (equivalent to human pubertal age) showed that rats in the LBW-vehicle group were marginally hyperactive compared with rats in the sham group, while rats in the LBW-B.breve group were significantly hypoactive compared with rats in the LBW-vehicle group. The gut microbiota in the LBW-vehicle group exhibited a profile significantly different from that in the sham group, whereas the gut microbiota in the LBW-B.breve group did not exhibit a significant difference from that in the sham group. Anatomical/histological evaluation at 6 weeks of age demonstrated that the brain weight and the cerebral areas on coronal sections were reduced in the LBW groups compared with the sham group. Probiotic supplementation did not ameliorate these morphological brain anomalies in LBW animals. The percentage of Iba-1+ cells in the brain was not different among the LBW-B.breve, LBW-vehicle, and sham groups. CONCLUSION Bifidobacterium breve supplementation during early life is suggested to have the potential to help children with LBW attenuate hypermobility in adolescence.
Collapse
Affiliation(s)
- Ayaka Itoh
- Department of Food and Nutrition, Kyoto Women's University, Kyoto, Japan
| | - Nao Tanaka
- Department of Food and Nutrition, Kyoto Women's University, Kyoto, Japan
| | - Sachiko Fukunaga
- Department of Food and Nutrition, Kyoto Women's University, Kyoto, Japan
| | - Akiko Nakano-Doi
- Laboratory of Neurogenesis and CNS Repair, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan.,Department of Therapeutic Progress in Brain Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan
| | - Tomohiro Matsuyama
- Department of Therapeutic Progress in Brain Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan
| | - Takayuki Nakagomi
- Laboratory of Neurogenesis and CNS Repair, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan.,Department of Therapeutic Progress in Brain Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan
| | - Masahiro Tsuji
- Department of Food and Nutrition, Kyoto Women's University, Kyoto, Japan
| |
Collapse
|
|
26
|
Saturio S, Nogacka AM, Alvarado-Jasso GM, Salazar N, de los Reyes-Gavilán CG, Gueimonde M, Arboleya S. Role of Bifidobacteria on Infant Health. Microorganisms 2021; 9:2415. [PMID: 34946017 PMCID: PMC8708449 DOI: 10.3390/microorganisms9122415] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/19/2021] [Accepted: 11/21/2021] [Indexed: 12/19/2022] Open
Abstract
Bifidobacteria are among the predominant microorganisms during infancy, being a dominant microbial group in the healthy breastfed infant and playing a crucial role in newborns and infant development. Not only the levels of the Bifidobacterium genus but also the profile and quantity of the different bifidobacterial species have been demonstrated to be of relevance to infant health. Although no definitive proof is available on the causal association, reduced levels of bifidobacteria are perhaps the most frequently observed alteration of the intestinal microbiota in infant diseases. Moreover, Bifidobacterium strains have been extensively studied by their probiotic attributes. This review compiles the available information about bifidobacterial composition and function since the beginning of life, describing different perinatal factors affecting them, and their implications on different health alterations in infancy. In addition, this review gathers exhaustive information about pre-clinical and clinical studies with Bifidobacterium strains as probiotics in neonates.
Collapse
Affiliation(s)
- Silvia Saturio
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (G.M.A.-J.); (N.S.); (C.G.d.l.R.-G.)
- Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), 33011 Oviedo, Spain
| | - Alicja M. Nogacka
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (G.M.A.-J.); (N.S.); (C.G.d.l.R.-G.)
- Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), 33011 Oviedo, Spain
| | - Guadalupe M. Alvarado-Jasso
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (G.M.A.-J.); (N.S.); (C.G.d.l.R.-G.)
| | - Nuria Salazar
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (G.M.A.-J.); (N.S.); (C.G.d.l.R.-G.)
- Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), 33011 Oviedo, Spain
| | - Clara G. de los Reyes-Gavilán
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (G.M.A.-J.); (N.S.); (C.G.d.l.R.-G.)
- Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), 33011 Oviedo, Spain
| | - Miguel Gueimonde
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (G.M.A.-J.); (N.S.); (C.G.d.l.R.-G.)
- Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), 33011 Oviedo, Spain
| | - Silvia Arboleya
- Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA-CSIC), 33300 Villaviciosa, Spain; (S.S.); (A.M.N.); (G.M.A.-J.); (N.S.); (C.G.d.l.R.-G.)
- Diet, Human Microbiota and Health Group, Institute of Health Research of the Principality of Asturias (ISPA), 33011 Oviedo, Spain
| |
Collapse
|
|
27
|
Plummer EL, Danielewski JA, Garland SM, Su J, Jacobs SE, Murray GL. The effect of probiotic supplementation on the gut microbiota of preterm infants. J Med Microbiol 2021; 70. [PMID: 34431764 PMCID: PMC8513625 DOI: 10.1099/jmm.0.001403] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Introduction. Probiotic supplementation of preterm infants may prevent serious morbidities associated with prematurity.Aim. To investigate the impact of probiotic supplementation on the gut microbiota and determine factors associated with detection of probiotic species in the infant gut.Hypothesis/Gap Statement. Probiotic supplementation increases the long-term colonization of probiotic species in the gut of preterm infants.Methodology. Longitudinal stool samples were collected from a cohort of very preterm infants participating in a blinded randomized controlled trial investigating the impact of probiotic supplementation (containing Bifidobacterium longum subsp. infantis BB-02, Bifidobacterium animalis subsp. lactis BB-12 and Streptococcus thermophilus TH-4) for prevention of late-onset sepsis. The presence of B. longum subsp. infantis, B. animalis subsp. lactis and S. thermophilus was determined for up to 23 months after supplementation ended using real-time PCR. Logistic regression was used to investigate the impact of probiotic supplementation on the presence of each species.Results. Detection of B. longum subsp. infantis [odds ratio (OR): 53.1; 95 % confidence interval (CI): 35.6-79.1; P < 0.001], B. animalis subsp. lactis (OR: 89.1; 95 % CI: 59.0-134.5; P < 0.001) and S. thermophilus (OR: 5.66; 95 % CI: 4.35-7.37; P < 0.001) was increased during the supplementation period in infants receiving probiotic supplementation. Post-supplementation, probiotic-supplemented infants had increased detection of B. longum subsp. infantis (OR: 2.53; 95 % CI: 1.64-3.90; P < 0.001) and B. animalis subsp. lactis (OR: 1.59; 95 % CI: 1.05-2.41; P=0.030). Commencing probiotic supplementation before 5 days from birth was associated with increased detection of the probiotic species over the study period (B. longum subsp. infantis, OR: 1.20; B. animalis subsp. lactis, OR: 1.28; S. thermophilus, OR: 1.45).Conclusion. Probiotic supplementation with B. longum subsp. infantis BB-02, B. animalis subsp. lactis BB-12 and S. thermophilus TH-4 enhances the presence of probiotic species in the gut microbiota of very preterm infants during and after supplementation. Commencing probiotic supplementation shortly after birth may be important for improving the long-term colonization of probiotic species.
Collapse
Affiliation(s)
- Erica L Plummer
- Centre for Women's Infectious Diseases Research, The Royal Women's Hospital, Parkville, Victoria, Australia.,Infection & Immunity Theme, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.,Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Jennifer A Danielewski
- Centre for Women's Infectious Diseases Research, The Royal Women's Hospital, Parkville, Victoria, Australia.,Infection & Immunity Theme, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
| | - Suzanne M Garland
- Centre for Women's Infectious Diseases Research, The Royal Women's Hospital, Parkville, Victoria, Australia.,Infection & Immunity Theme, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.,Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia
| | - Jenny Su
- Centre for Women's Infectious Diseases Research, The Royal Women's Hospital, Parkville, Victoria, Australia.,Infection & Immunity Theme, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
| | - Susan E Jacobs
- Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia.,Neonatal Services, The Royal Women's Hospital, Parkville, Victoria, Australia.,Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
| | - Gerald L Murray
- Centre for Women's Infectious Diseases Research, The Royal Women's Hospital, Parkville, Victoria, Australia.,Infection & Immunity Theme, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.,Department of Obstetrics and Gynaecology, University of Melbourne, Parkville, Victoria, Australia
| |
Collapse
|
|
28
|
黎 杰, 何 志, 王 伟, 林 才. [Efficacy of probiotics in preventing late-onset sepsis in very low birth weight infants: a Meta analysis]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2021; 23:599-607. [PMID: 34130782 PMCID: PMC8214000 DOI: 10.7499/j.issn.1008-8830.2012014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 04/03/2021] [Indexed: 06/12/2023]
Abstract
OBJECTIVE To study the efficacy of probiotics in preventing late-onset sepsis (LOS) in very low birth weight (VLBW) infants. METHODS Databases including PubMed, Web of Science, Cochrane Library, Wanfang Data, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database were searched for randomized controlled trials (RCTs) of probiotics in preventing LOS in VLBW infants. LOS was classified as clinical LOS and confirmed LOS. RevMan 5.4 was used to perform the Meta analysis. RESULTS A total of 31 RCTs were included, with 3 490 VLBW infants in the probiotics group and 3 376 VLBW infants in the control group. The Meta analysis showed that compared with the control group, the probiotics group had significantly lower risks of clinical LOS (RR=0.79, 95%CI:0.66-0.94, P=0.009) and clinical/confirmed LOS (RR=0.79, 95% CI:0.67-0.94, P=0.007). In the probiotics group, the infants receiving exclusive breastfeeding had a significantly lower risk of confirmed LOS (RR=0.77, 95%CI:0.62-0.96, P=0.02). CONCLUSIONS Current evidence indicates that probiotics may reduce the risk of clinical LOS and clinical/confirmed LOS in VLBW infants, and the risk of confirmed LOS in VLBW infants who are exclusively breastfed.
Collapse
Affiliation(s)
- 杰勇 黎
- />肇庆市第一人民医院新生儿科, 广东肇庆 526000Department of Neonatology, First People's Hospital of Zhaoqing, Zhaoqing, Guangdong 526000, China
| | - 志勋 何
- />肇庆市第一人民医院新生儿科, 广东肇庆 526000Department of Neonatology, First People's Hospital of Zhaoqing, Zhaoqing, Guangdong 526000, China
| | - 伟名 王
- />肇庆市第一人民医院新生儿科, 广东肇庆 526000Department of Neonatology, First People's Hospital of Zhaoqing, Zhaoqing, Guangdong 526000, China
| | - 才 林
- />肇庆市第一人民医院新生儿科, 广东肇庆 526000Department of Neonatology, First People's Hospital of Zhaoqing, Zhaoqing, Guangdong 526000, China
| |
Collapse
|
|
29
|
Horigome A, Hisata K, Odamaki T, Iwabuchi N, Xiao JZ, Shimizu T. Colonization of Supplemented Bifidobacterium breve M-16V in Low Birth Weight Infants and Its Effects on Their Gut Microbiota Weeks Post-administration. Front Microbiol 2021; 12:610080. [PMID: 33897631 PMCID: PMC8058467 DOI: 10.3389/fmicb.2021.610080] [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: 09/25/2020] [Accepted: 03/17/2021] [Indexed: 12/12/2022] Open
Abstract
The colonization and persistence of probiotics introduced into the adult human gut appears to be limited. It is uncertain, however, whether probiotics can successfully colonize the intestinal tracts of full-term and premature infants. In this study, we investigated the colonization and the effect of oral supplementation with Bifidobacterium breve M-16V on the gut microbiota of low birth weight (LBW) infants. A total of 22 LBW infants (12 infants in the M-16V group and 10 infants in the control group) were enrolled. B. breve M-16V was administrated to LBW infants in the M-16V group from birth until hospital discharge. Fecal samples were collected from each subject at weeks (3.7-9.3 weeks in the M-16V group and 2.1-6.1 weeks in the control group) after discharge. qPCR analysis showed that the administrated strain was detected in 83.3% of fecal samples in the M-16V group (at log10 8.33 ± 0.99 cell numbers per gram of wet feces), suggesting that this strain colonized most of the infants beyond several weeks post-administration. Fecal microbiota analysis by 16S rRNA gene sequencing showed that the abundance of Actinobacteria was significantly higher (P < 0.01), whereas that of Proteobacteria was significantly lower (P < 0.001) in the M-16V group as compared with the control group. Notably, the levels of the administrated strain and indigenous Bifidobacterium bacteria were both significantly higher in the M-16V group than in the control group. Our findings suggest that oral administration of B. breve M-16V led to engraftment for at least several weeks post-administration and we observed a potential overall improvement in microbiota formation in the LBW infants' guts.
Collapse
Affiliation(s)
- Ayako Horigome
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | - Ken Hisata
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Toshitaka Odamaki
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | - Noriyuki Iwabuchi
- Food Ingredients and Technology Institute, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | - Jin-Zhong Xiao
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., Kanagawa, Japan
| | - Toshiaki Shimizu
- Department of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan
| |
Collapse
|
|
30
|
Hortensius LM, van den Hooven EH, Dudink J, Tataranno ML, van Elburg RM, Benders MJNL. NutriBrain: protocol for a randomised, double-blind, controlled trial to evaluate the effects of a nutritional product on brain integrity in preterm infants. BMC Pediatr 2021; 21:132. [PMID: 33731062 PMCID: PMC7968155 DOI: 10.1186/s12887-021-02570-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Accepted: 02/24/2021] [Indexed: 11/23/2022] Open
Abstract
Background The gut microbiota and the brain are connected through different mechanisms. Bacterial colonisation of the gut plays a substantial role in normal brain development, providing opportunities for nutritional neuroprotective interventions that target the gut microbiome. Preterm infants are at risk for brain injury, especially white matter injury, mediated by inflammation and infection. Probiotics, prebiotics and L-glutamine are nutritional components that have individually already demonstrated beneficial effects in preterm infants, mostly by reducing infections or modulating the inflammatory response. The NutriBrain study aims to evaluate the benefits of a combination of probiotics, prebiotics and L-glutamine on white matter microstructure integrity (i.e., development of white matter tracts) at term equivalent age in very and extremely preterm born infants. Methods This study is a double-blind, randomised, controlled, parallel-group, single-center study. Eighty-eight infants born between 24 + 0 and < 30 + 0 weeks gestational age and less than 72 h old will be randomised after parental informed consent to receive either active study product or placebo. Active study product consists of a combination of Bifidobacterium breve M-16V, short-chain galacto-oligosaccharides, long-chain fructo-oligosaccharides and L-glutamine and will be given enterally in addition to regular infant feeding from 48 to 72 h after birth until 36 weeks postmenstrual age. The primary study outcome of white matter microstructure integrity will be measured as fractional anisotropy, assessed using magnetic resonance diffusion tensor imaging at term equivalent age and analysed using Tract-Based Spatial Statistics. Secondary outcomes are white matter injury, brain tissue volumes and cortical morphology, serious neonatal infections, serum inflammatory markers and neurodevelopmental outcome. Discussion This study will be the first to evaluate the effect of a combination of probiotics, prebiotics and L-glutamine on brain development in preterm infants. It may give new insights in the development and function of the gut microbiota and immune system in relation to brain development and provide a new, safe treatment possibility to improve brain development in the care for preterm infants. Trial registration ISRCTN, ISRCTN96620855. Date assigned: 10/10/2017. Supplementary Information The online version contains supplementary material available at 10.1186/s12887-021-02570-x.
Collapse
Affiliation(s)
- Lisa M Hortensius
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.,University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands
| | | | - Jeroen Dudink
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.,University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands
| | - Maria Luisa Tataranno
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.,University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands
| | - Ruurd M van Elburg
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.,Emma Children's Hospital, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Manon J N L Benders
- Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. .,University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.
| |
Collapse
|
|
31
|
Imdad A, Rehman F, Davis E, Ranjit D, Surin GSS, Attia SL, Lawler S, Smith AA, Bhutta ZA. Effects of neonatal nutrition interventions on neonatal mortality and child health and development outcomes: A systematic review. CAMPBELL SYSTEMATIC REVIEWS 2021; 17:e1141. [PMID: 37133295 PMCID: PMC8356300 DOI: 10.1002/cl2.1141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
Background The last two decades have seen a significant decrease in mortality for children <5 years of age in low and middle-income countries (LMICs); however, neonatal (age, 0-28 days) mortality has not decreased at the same rate. We assessed three neonatal nutritional interventions that have the potential of reducing morbidity and mortality during infancy in LMICs. Objectives To determine the efficacy and effectiveness of synthetic vitamin A, dextrose oral gel, and probiotic supplementation during the neonatal period. Search Methods We conducted electronic searches for relevant studies on the following databases: PubMed, CINAHL, LILACS, SCOPUS, and CENTRAL, Cochrane Central Register for Controlled Trials, up to November 27, 2019. Selection Criteria We aimed to include randomized and quasi-experimental studies. The target population was neonates in LMICs. The interventions included synthetic vitamin A supplementation, oral dextrose gel supplementation, and probiotic supplementation during the neonatal period. We included studies from the community and hospital settings irrespective of the gestational age or birth weight of the neonate. Data Collection and Analysis Two authors screened the titles and extracted the data from selected studies. The risk of bias (ROB) in the included studies was assessed according to the Cochrane Handbook of Systematic Reviews. The primary outcome was all-cause mortality. The secondary outcomes were neonatal sepsis, necrotizing enterocolitis (NEC), prevention and treatment of neonatal hypoglycaemia, adverse events, and neurodevelopmental outcomes. Data were meta-analyzed by random effect models to obtain relative risk (RR) and 95% confidence interval (CI) for dichotomous outcomes and mean difference with 95% CI for continuous outcomes. The overall rating of evidence was determined by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Main Results Sixteen randomized studies (total participants 169,366) assessed the effect of vitamin A supplementation during the neonatal period. All studies were conducted in low- and middle-income (LMIC) countries. Thirteen studies were conducted in the community setting and three studies were conducted in the hospital setting, specifically in neonatal intensive care units. Studies were conducted in 10 different countries including India (four studies), Guinea-Bissau (three studies), Bangladesh (two studies), and one study each in China, Ghana, Indonesia, Nepal, Pakistan, Tanzania, and Zimbabwe. The overall ROB was low in most of the included studies for neonatal vitamin A supplementation. The pooled results from the community based randomized studies showed that there was no significant difference in all-cause mortality in the vitamin A (intervention) group compared to controls at 1 month (RR, 0.99; 95% CI, 0.90-1.08; six studies with 126,548 participants, statistical heterogeneity I 2 0%, funnel plot symmetrical, grade rating high), 6 months (RR, 0.98; 95% CI, 0.89-1.07; 12 studies with 154,940 participants, statistical heterogeneity I 2 43%, funnel plot symmetrical, GRADE quality high) and 12 months of age (RR, 1.04; 95% CI, 0.94-1.14; eight studies with 118,376 participants, statistical heterogeneity I 2 46%, funnel plot symmetrical, GRADE quality high). Neonatal vitamin A supplementation increased the incidence of bulging fontanelle by 53% compared to control (RR, 1.53; 95% CI, 1.12-2.09; six studies with 100,256 participants, statistical heterogeneity I 2 65%, funnel plot symmetrical, GRADE quality high). We did not identify any experimental study that addressed the use of dextrose gel for the prevention and/or treatment of neonatal hypoglycaemia in LMIC. Thirty-three studies assessed the effect of probiotic supplementation during the neonatal period (total participants 11,595; probiotics: 5854 and controls: 5741). All of the included studies were conducted in LMIC and were randomized. Most of the studies were done in the hospital setting and included participants who were preterm (born < 37 weeks gestation) and/or low birth weight (<2500 g birth weight). Studies were conducted in 13 different countries with 10 studies conducted in India, six studies in Turkey, three studies each in China and Iran, two each in Mexico and South Africa, and one each in Bangladesh, Brazil, Colombia, Indonesia, Nepal, Pakistan, and Thailand. Three studies were at high ROB due to lack of appropriate randomization sequence or allocation concealment. Combined data from 25 studies showed that probiotic supplementation reduced all-cause mortality by 20% compared to controls (RR, 0.80; 95% CI, 0.66-0.96; total number of participants 10,998, number needed to treat 100, statistical heterogeneity I 2 0%, funnel plot symmetrical, GRADE quality high). Twenty-nine studies reported the effect of probiotics on the incidence of NEC, and the combined results showed a relative reduction of 54% in the intervention group compared to controls (RR, 0.46; 95% CI, 0.35-0.59; total number of participants 5574, number needed to treat 17, statistical heterogeneity I 2 24%, funnel plot symmetrical, GRADE quality high). Twenty-one studies assessed the effect of probiotic supplementation during the neonatal period on neonatal sepsis, and the combined results showed a relative reduction of 22% in the intervention group compared to controls (RR, 0.78; 95% CI, 0.70-0.86; total number of participants 9105, number needed to treat 14, statistical heterogeneity I 2 23%, funnel plot symmetrical, GRADE quality high). Authors' Conclusions Vitamin A supplementation during the neonatal period does not reduce all-cause neonatal or infant mortality in LMICs in the community setting. However, neonatal vitamin A supplementation increases the risk of Bulging Fontanelle. No experimental or quasi-experimental studies were available from LMICs to assess the effect of dextrose gel supplementation for the prevention or treatment of neonatal hypoglycaemia. Probiotic supplementation during the neonatal period seems to reduce all-cause mortality, NEC, and sepsis in babies born with low birth weight and/or preterm in the hospital setting. There was clinical heterogeneity in the use of probiotics, and we could not recommend any single strain of probiotics for wider use based on these results. There was a lack of studies on probiotic supplementation in the community setting. More research is needed to assess the effect of probiotics administered to neonates in-home/community setting in LMICs.
Collapse
Affiliation(s)
- Aamer Imdad
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and NutritionSUNY Upstate Medical UniversitySyracuseNew YorkUSA
| | - Faseeha Rehman
- Department of MedicineRaritan Bay Medical CenterPerth AmboyNew YorkUSA
| | - Evans Davis
- Roswell Park Comprehensive Cancer Center, Department of Cancer Prevention and ControlUniversity of BuffaloBuffaloNew YorkUSA
| | - Deepika Ranjit
- College of MedicineSUNY Upstate Medical UniversitySyracuseNew YorkUSA
| | | | - Suzanna L. Attia
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and NutritionUniversity of KentuckyLexingtonKentuckyUSA
| | - Sarah Lawler
- Health Science LibrarySUNY Upstate Medical UniversitySyracuseNew YorkUSA
| | - Abigail A. Smith
- Health Science LibraraySUNY Upstate Medical UniversitySyracuseNew YorkUSA
| | - Zulfiqar A. Bhutta
- Centre for Global Child HealthThe Hospital for Sick ChildrenTorontoOntarioCanada
| |
Collapse
|
|
32
|
Qi M, Tan B, Wang J, Liao S, Deng Y, Ji P, Song T, Zha A, Yin Y. The microbiota-gut-brain axis: A novel nutritional therapeutic target for growth retardation. Crit Rev Food Sci Nutr 2021; 62:4867-4892. [PMID: 33523720 DOI: 10.1080/10408398.2021.1879004] [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] [Indexed: 12/14/2022]
Abstract
Growth retardation (GR), which commonly occurs in childhood, is a major health concern globally. However, the specific mechanism remains unclear. It has been increasingly recognized that changes in the gut microbiota may lead to GR through affecting the microbiota-gut-brain axis. Microbiota interacts with multiple factors such as birth to affect the growth of individuals. Microbiota communicates with the nerve system through chemical signaling (direct entry into the circulation system or stimulation of enteroendocrine cells) and nervous signaling (interaction with enteric nerve system and vagus nerve), which modulates appetite and immune response. Besides, they may also influence the function of enteric glial cells or lymphocytes and levels of systemic inflammatory cytokines. Environmental stress may cause leaky gut through perturbing the hypothalamic-pituitary-adrenal axis to further result in GR. Nutritional therapies involving probiotics and pre-/postbiotics are being investigated for helping the patients to overcome GR. In this review, we summarize the role of microbiota in GR with human and animal models. Then, existing and potential regulatory mechanisms are reviewed, especially the effect of microbiota-gut-brain axis. Finally, we propose nutritional therapeutic strategies for GR by the intervention of microbiota-gut-brain axis, which may provide novel perspectives for the treatment of GR in humans and animals.
Collapse
Affiliation(s)
- Ming Qi
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China.,College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Bie Tan
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China.,College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, China
| | - Jing Wang
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China
| | - Simeng Liao
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Yuankun Deng
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China.,College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, China
| | - Peng Ji
- Department of Nutrition, University of California, Davis, California, USA
| | - Tongxing Song
- College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China
| | - Andong Zha
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Yulong Yin
- Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Processes in Subtropical Region, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan, China.,College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, China
| |
Collapse
|
|
33
|
Beghetti I, Panizza D, Lenzi J, Gori D, Martini S, Corvaglia L, Aceti A. Probiotics for Preventing Necrotizing Enterocolitis in Preterm Infants: A Network Meta-Analysis. Nutrients 2021; 13:nu13010192. [PMID: 33435456 PMCID: PMC7827781 DOI: 10.3390/nu13010192] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Revised: 12/28/2020] [Accepted: 01/05/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Recent evidence supports a role of probiotics in preventing necrotizing enterocolitis (NEC) in preterm infants. METHODS A systematic review and network meta-analysis of randomized controlled trials (RCTs) on the role of probiotics in preventing NEC in preterm infants, focusing on the differential effect of type of feeding, was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A random-effects model was used; a subgroup analysis on exclusively human milk (HM)-fed infants vs. infants receiving formula (alone or with HM) was performed. RESULTS Fifty-one trials were included (10,664 infants, 29 probiotic interventions); 31 studies (19 different probiotic regimens) were suitable for subgroup analysis according to feeding. In the overall analysis, Lactobacillus acidophilus LB revealed the most promising effect for reducing NEC risk (odds ratio (OR), 0.03; 95% credible intervals (CrIs), 0.00-0.21). The subgroup analysis showed that Bifidobacterium lactis Bb-12/B94 was associated with a reduced risk of NEC stage ≥2 in both feeding type populations, with a discrepancy in the relative effect size in favour of exclusively HM-fed infants (OR 0.04; 95% CrIs <0.01-0.49 vs. OR 0.32; 95% CrIs 0.10-0.36). CONCLUSIONS B. lactis Bb-12/B94 could reduce NEC risk with a different size effect according to feeding type. Of note, most probiotic strains are evaluated in few trials and relatively small populations, and outcome data according to feeding type are not available for all RCTs. Further trials are needed to confirm the present findings.
Collapse
Affiliation(s)
- Isadora Beghetti
- Neonatal Intensive Care Unit, AOU Bologna, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy; (I.B.); (S.M.); (L.C.); (A.A.)
| | - Davide Panizza
- Neonatal Intensive Care Unit, AOU Bologna, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy; (I.B.); (S.M.); (L.C.); (A.A.)
- Correspondence: ; Tel.: +39-051-342754
| | - Jacopo Lenzi
- Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126 Bologna, Italy; (J.L.); (D.G.)
| | - Davide Gori
- Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, 40126 Bologna, Italy; (J.L.); (D.G.)
| | - Silvia Martini
- Neonatal Intensive Care Unit, AOU Bologna, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy; (I.B.); (S.M.); (L.C.); (A.A.)
| | - Luigi Corvaglia
- Neonatal Intensive Care Unit, AOU Bologna, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy; (I.B.); (S.M.); (L.C.); (A.A.)
| | - Arianna Aceti
- Neonatal Intensive Care Unit, AOU Bologna, Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy; (I.B.); (S.M.); (L.C.); (A.A.)
| |
Collapse
|
|
34
|
Chi C, Li C, Buys N, Wang W, Yin C, Sun J. Effects of Probiotics in Preterm Infants: A Network Meta-analysis. Pediatrics 2021; 147:peds.2020-0706. [PMID: 33323491 DOI: 10.1542/peds.2020-0706] [Citation(s) in RCA: 61] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/09/2020] [Indexed: 11/24/2022] Open
Abstract
CONTEXT Probiotics have proven to be effective in promoting premature infants' health, but the optimal usage is unknown. OBJECTIVE To compare probiotic supplements for premature infants. DATA SOURCES We searched PubMed, Embase, Cochrane, and ProQuest from inception of these databases to June 1, 2020. STUDY SELECTION Randomized trials of probiotic supplement intervention for preterm infants were screened by 2 reviewers independently. The primary outcomes were mortality and the morbidity of necrotizing enterocolitis (NEC). Secondary outcomes were morbidity of sepsis, time to achieve full enteral feeding, and length of hospital stay. DATA EXTRACTION The data of primary and secondary outcomes were extracted by 2 reviewers and pooled with a random-effects model. RESULTS The meta-analysis included 45 trials with 12 320 participants. Bifidobacterium plus Lactobacillus was associated with lower rates of mortality (risk ratio 0.56; 95% credible interval 0.34-0.84) and NEC morbidity (0.47; 0.27-0.79) in comparison to the placebo; Lactobacillus plus prebiotic was associated with lower rates of NEC morbidity (0.06; 0.01-0.41) in comparison to the placebo; Bifidobacterium plus prebiotic had the highest probability of having the lowest rate of mortality (surface under the cumulative ranking curve 83.94%); and Lactobacillus plus prebiotic had the highest probability of having the lowest rate of NEC (surface under the cumulative ranking curve 95.62%). LIMITATIONS In few studies did authors report the data of infants with a lower birth weight or gestational age. CONCLUSIONS The efficacy of single probiotic supplements is limited, compared to combined use of probiotics. To achieve optimal effect on premature infant health, combined use of prebiotic and probiotic, especially Lactobacillus or Bifidobacterium, is recommended.
Collapse
Affiliation(s)
- Cheng Chi
- School of Nursing, Jining Medical University, Jining, China.,Department of Internal Medicine, Beijing Obstetrics and Gynecology Hospital and Capital Medical University, Beijing, China; and.,School of Medicine and
| | - Cheng Li
- School of Nursing, Jining Medical University, Jining, China; .,Department of Internal Medicine, Beijing Obstetrics and Gynecology Hospital and Capital Medical University, Beijing, China; and
| | - Nicholas Buys
- Menzies Health Institute Queensland, Griffith University, Gold Coast, Australia
| | - Wenjun Wang
- School of Nursing, Jining Medical University, Jining, China
| | - Chenghong Yin
- Department of Internal Medicine, Beijing Obstetrics and Gynecology Hospital and Capital Medical University, Beijing, China; and
| | | |
Collapse
|
|
35
|
Agrawal S, Pestell CF, Granich J, Rao S, Nathan E, Wray JA, Whitehouse AJO, Patole S. Difficulties in developmental follow-up of preterm neonates in a randomised-controlled trial of Bifidobacterium breve M16-V - Experience from Western Australia. Early Hum Dev 2020; 151:105165. [PMID: 32871454 DOI: 10.1016/j.earlhumdev.2020.105165] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 07/20/2020] [Accepted: 08/19/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Probiotics may be neuroprotective for preterm neonates due to their anti-inflammatory effects and ability to facilitate nutrition. AIM To assess long-term effects of early probiotic supplementation on neuropsychological development in preterm infants. STUDY DESIGN Follow up study. SUBJECTS Children at age 3 to 5 years who had participated as preterm infants (<33 week) in the randomised controlled trial. OUTCOMES Primary: Continuous early learning composite measure derived from the Mullen's Scale of Early Learning (MSEL). Other outcomes were assessed by the Developmental, Dimensional and Diagnostic Interview, Developmental NEuroPSYchological assessment-2nd Edition, Parental questionnaires using children's communication checklist-2nd edition, social responsiveness scale, and Vineland Adaptive Behavioural Scales-2nd edition. MEASURES Continuous scores derived from all the measures. RESULTS 67 children of the 159 participants (42%) (Probiotic: 36/79, Placebo: 31/80) were followed-up for at least one neuropsychological assessment. All six assessments were completed in 18/31 (58.1%) of the control vs. 11/36 (30.6%) probiotic group children. Multivariable analysis of MSEL composite score showed no evidence of probiotic effect univariately, or after adjustment for gestation, intrauterine growth restriction, Apgar <7 at 5 min and age at assessment (adjusted mean effect in probiotic group: -2.7, 95% CI -8.5-3.0, p = 0.349). CONCLUSION There was no significant effect on neurodevelopment of children assessed at the age of 3 to 5 years who participated as preterm neonates in the RCT of B. breve M-16V. The validity of these results is limited by the reduced sample size due to high rate of loss to follow up.
Collapse
Affiliation(s)
- S Agrawal
- Neonatal Directorate, KEM Hospital for Women, 374 Bagot Road, Subiaco, WA, Australia.
| | - C F Pestell
- School of Psychological Science, University of WA, 35 Stirling Highway, Crawley, WA, 6009 Perth, Australia; Telethon Kids Institute, 15 Hospital Avenue, Nedlands, WA, 6009 Perth, Australia
| | - J Granich
- Telethon Kids Institute, 15 Hospital Avenue, Nedlands, WA, 6009 Perth, Australia
| | - S Rao
- School of Medicine, University of WA, 35 Stirling Highway, Crawley, WA, 6009 Perth, Australia; Neonatal Pediatrics, Perth Children Hospital, 15 Hospital Avenue, Nedlands, WA, 6009 Perth, Australia
| | - E Nathan
- School of Medicine, University of WA, 35 Stirling Highway, Crawley, WA, 6009 Perth, Australia; Women and Infants Research Foundation, King Edward Memorial Hospital for Women, 374, Bagot Road, Subiaco, Perth, WA, Australia
| | - J A Wray
- School of Medicine, University of WA, 35 Stirling Highway, Crawley, WA, 6009 Perth, Australia; Child Development Centre, 4/16 Rheola St, West Perth, WA 6005, Australia
| | - A J O Whitehouse
- Telethon Kids Institute, 15 Hospital Avenue, Nedlands, WA, 6009 Perth, Australia
| | - S Patole
- Neonatal Directorate, KEM Hospital for Women, 374 Bagot Road, Subiaco, WA, Australia; School of Medicine, University of WA, 35 Stirling Highway, Crawley, WA, 6009 Perth, Australia
| |
Collapse
|
|
36
|
Sharif S, Meader N, Oddie SJ, Rojas-Reyes MX, McGuire W. Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Cochrane Database Syst Rev 2020; 10:CD005496. [PMID: 33058137 PMCID: PMC8094746 DOI: 10.1002/14651858.cd005496.pub5] [Citation(s) in RCA: 76] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Intestinal dysbiosis may contribute to the pathogenesis of necrotising enterocolitis (NEC) in very preterm or very low birth weight infants. Dietary supplementation with probiotics to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of NEC and associated mortality and morbidity. OBJECTIVES: To determine the effect of supplemental probiotics on the risk of NEC and mortality and morbidity in very preterm or very low birth weight infants. SEARCH METHODS We searched Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 2) in the Cochrane Library; MEDLINE Ovid (1946 to 17 Feb 2020), Embase Ovid (1974 to 17 Feb 2020), Maternity & Infant Care Database Ovid (1971 to 17 Feb 2020), the Cumulative Index to Nursing and Allied Health Literature (1982 to 18 Feb 2020). We searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA We included RCTs and quasi-RCTs comparing probiotic supplementation with placebo or no probiotics in very preterm or very low birth weight infants. DATA COLLECTION AND ANALYSIS We used the standard methods of Cochrane Neonatal. Two review authors separately evaluated trial quality, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of evidence for effects on NEC, all-cause mortality, late-onset infection, and severe neurodevelopmental impairment. MAIN RESULTS We included 56 trials in which 10,812 infants participated. Most trials were small (median sample size 149). Lack of clarity on methods to conceal allocation and mask caregivers or investigators were the main potential sources of bias in about half of the trials. Trials varied by the formulation of the probiotics. The most commonly used preparations contained Bifidobacterium spp., Lactobacillus spp., Saccharomyces spp., and Streptococcus spp. alone or in combinations. Meta-analysis showed that probiotics may reduce the risk of NEC: RR 0.54, 95% CI 0.45 to 0.65 (54 trials, 10,604 infants; I² = 17%); RD -0.03, 95% CI -0.04 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) 33, 95% CI 25 to 50. Evidence was assessed as low certainty because of the limitations in trials design, and the presence of funnel plot asymmetry consistent with publication bias. Sensitivity meta-analysis of trials at low risk of bias showed a reduced risk of NEC: RR 0.70, 95% CI 0.55 to 0.89 (16 trials, 4597 infants; I² = 25%); RD -0.02, 95% CI -0.03 to -0.01; NNTB 50, 95% CI 33 to 100. Meta-analyses showed that probiotics probably reduce mortality (RR 0.76, 95% CI 0.65 to 0.89; (51 trials, 10,170 infants; I² = 0%); RD -0.02, 95% CI -0.02 to -0.01; NNTB 50, 95% CI 50 to 100), and late-onset invasive infection (RR 0.89, 95% CI 0.82 to 0.97; (47 trials, 9762 infants; I² = 19%); RD -0.02, 95% CI -0.03 to -0.01; NNTB 50, 95% CI 33 to 100). Evidence was assessed as moderate certainty for both these outcomes because of the limitations in trials design. Sensitivity meta-analyses of 16 trials (4597 infants) at low risk of bias did not show an effect on mortality or infection. Meta-analysis showed that probiotics may have little or no effect on severe neurodevelopmental impairment (RR 1.03, 95% CI 0.84 to 1.26 (five trials, 1518 infants; I² = 0%). The certainty on this evidence is low because of limitations in trials design and serious imprecision of effect estimate. Few data (from seven of the trials) were available for extremely preterm or extremely low birth weight infants. Meta-analyses did not show effects on NEC, death, or infection (low-certainty evidence). AUTHORS' CONCLUSIONS Given the low to moderate level of certainty about the effects of probiotic supplements on the risk of NEC and associated morbidity and mortality for very preterm or very low birth weight infants, and particularly for extremely preterm or extremely low birth weight infants, further, large, high-quality trials are needed to provide evidence of sufficient quality and applicability to inform policy and practice.
Collapse
Affiliation(s)
- Sahar Sharif
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Nicholas Meader
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Sam J Oddie
- Centre for Reviews and Dissemination, University of York, York, UK
- Bradford Neonatology, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK
| | - Maria Ximena Rojas-Reyes
- Department of Clinical Epidemiology and Public Health, Institut de Recerca Hospital Santa Creu i Sant Pau, Barcelona, Spain
| | - William McGuire
- Centre for Reviews and Dissemination, University of York, York, UK
| |
Collapse
|
|
37
|
Athalye-Jape G, Nettleton M, Lai CT, Nathan E, Geddes D, Simmer K, Patole S. Composition of Coloured Gastric Residuals in Extremely Preterm Infants-A Nested Prospective Observational Study. Nutrients 2020; 12:nu12092585. [PMID: 32858860 PMCID: PMC7551671 DOI: 10.3390/nu12092585] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 08/21/2020] [Accepted: 08/23/2020] [Indexed: 01/08/2023] Open
Abstract
Green gastric residuals (GR) are often considered as a sign of feed intolerance and discarded in preterm infants. Probiotics are known to enhance feed tolerance in preterm infants. To assess the composition (primary outcome) and volume of discarded green GRs, and feeding outcomes in extremely preterm (EP) infants in a probiotic trial, composition of pale and dark green GRs in the first two weeks of life from EP infants (<28 weeks) in a randomized controlled trial (RCT: SiMPro) of single vs. three-strain probiotics was assessed. Feeding outcomes included time to full feeds (TFF: 150 mL/kg/day) and duration of parenteral nutrition (PN). EP infants given placebo in our previous probiotic RCT served as the reference group. Analysis involved linear regression modelling with clustered standard errors for repeated measurements. GRs of 74/103 from 39 SiMPro infants (18: single-strain, 21: three-strain) were analyzed. Bile acid content was higher but statistically insignificant (825.79 vs. 338.1 µmol/L; p = 0.12) in dark vs. pale green GRs. Mean (95% confidence interval) fat, nitrogen, and carbohydrate loss in GRs over the study period was 0.02 g (0.01–0.03), 0.011 g (0.009–0.013), and 0.05 g (0.04–0.06), respectively. Overall, SiMPro infants had shorter median TFF (10 vs. 14 days, p = 0.02) and duration of PN (10 vs. 16 days, p = 0.022) compared with control group infants. Z scores for growth parameters at discharge were comparable. Discarding dark green GRs meant higher loss of bile acids during early enteral nutrition in EP infants. Probiotic supplementation was associated with reduced TFF and duration of PN.
Collapse
Affiliation(s)
- Gayatri Athalye-Jape
- Neonatal Directorate, King Edward Memorial Hospital, Perth 6008, Western Australia, Australia; (G.A.-J.); (M.N.); (K.S.)
- Centre for Neonatal Research and Education and Division of Paediatrics, Medical School, University of Western Australia, Perth 6008, Western Australia, Australia
| | - Megan Nettleton
- Neonatal Directorate, King Edward Memorial Hospital, Perth 6008, Western Australia, Australia; (G.A.-J.); (M.N.); (K.S.)
| | - Ching-Tat Lai
- School of Molecular Sciences, University of Western Australia, Perth 6009, Western Australia, Australia; (C.-T.L.); (D.G.)
| | - Elizabeth Nathan
- Department of Biostatistics, Women and Infants Research Foundation, Perth 6008, Western Australia, Australia;
- Division of Obstetrics and Gynaecology, University of Western Australia, Perth 6008, Western Australia, Australia
| | - Donna Geddes
- School of Molecular Sciences, University of Western Australia, Perth 6009, Western Australia, Australia; (C.-T.L.); (D.G.)
| | - Karen Simmer
- Neonatal Directorate, King Edward Memorial Hospital, Perth 6008, Western Australia, Australia; (G.A.-J.); (M.N.); (K.S.)
- Centre for Neonatal Research and Education and Division of Paediatrics, Medical School, University of Western Australia, Perth 6008, Western Australia, Australia
| | - Sanjay Patole
- Neonatal Directorate, King Edward Memorial Hospital, Perth 6008, Western Australia, Australia; (G.A.-J.); (M.N.); (K.S.)
- Centre for Neonatal Research and Education and Division of Paediatrics, Medical School, University of Western Australia, Perth 6008, Western Australia, Australia
- Correspondence: ; Tel.: +61-893401260
| |
Collapse
|
|
38
|
Sato N, Yuzawa M, Aminul MI, Tomokiyo M, Albarracin L, Garcia-Castillo V, Ideka-Ohtsubo W, Iwabuchi N, Xiao JZ, Garcia-Cancino A, Villena J, Kitazawa H. Evaluation of Porcine Intestinal Epitheliocytes as an In vitro Immunoassay System for the Selection of Probiotic Bifidobacteria to Alleviate Inflammatory Bowel Disease. Probiotics Antimicrob Proteins 2020; 13:824-836. [PMID: 32779098 DOI: 10.1007/s12602-020-09694-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The use of in vitro systems that allow efficient selection of probiotic candidates with immunomodulatory properties could significantly minimize the use of experimental animals. In this work, we generated an in vitro immunoassay system based on porcine intestinal epithelial (PIE) cells and dextran sodium sulfate (DSS) administration that could be useful for the selection and characterization of potential probiotic strains to be used in inflammatory bowel disease (IBD) patients. Our strategy was based on two fundamental pillars: on the one hand, the capacity of PIE cells to create a monolayer by attaching to neighboring cells and efficiently mount inflammatory responses and, on the other hand, the use of two probiotic bifidobacteria strains that have been characterized in terms of their immunomodulatory capacities, particularly in mouse IBD models and patients. Our results demonstrated that DSS administration can alter the epithelial barrier created in vitro by PIE cells and induce a potent inflammatory response, characterized by increases in the expression levels of several inflammatory factors including TNF-α, IL-1α, CCL4, CCL8, CCL11, CXCL5, CXCL9, CXCL10, SELL, SELE, EPCAM, VCAM, NCF2, and SAA2. In addition, we demonstrated that Bifidobacterium breve M-16V and B. longum BB536 are able to regulate the C-jun N-terminal kinase (JNK) intracellular signalling pathway, reducing the DSS-induced alterations of the in vitro epithelial barrier and differentially regulating the inflammatory response in a strain-dependent fashion. The good correlation between our in vitro findings in PIE cells and previous studies in animal models and IBD patients shows the potential value of our system to select new probiotic candidates in an efficient way.
Collapse
Affiliation(s)
- Nana Sato
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan.,Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Mao Yuzawa
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan.,Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Md Islam Aminul
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan.,Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Mikado Tomokiyo
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan.,Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Leonardo Albarracin
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan.,Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), San Miguel de Tucuman, Tucuman, Argentina.,Laboratory of Computing Science, Faculty of Exact Sciences and Technology, Tucuman University, San Miguel de Tucuman, Tucuman, Argentina
| | - Valeria Garcia-Castillo
- Laboratory of Bacterial Pathogenicity, Faculty of Biological Sciences, University of Concepcion, Concepcion, Chile
| | - Wakako Ideka-Ohtsubo
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan.,Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan
| | - Noriyuki Iwabuchi
- Food Science and Technology Institute, Morinaga Milk Industry Co. Ltd, Zama, Kanagawa, Japan
| | - Jin-Zhong Xiao
- Food Science and Technology Institute, Morinaga Milk Industry Co. Ltd, Zama, Kanagawa, Japan
| | - Apolinaria Garcia-Cancino
- Laboratory of Bacterial Pathogenicity, Faculty of Biological Sciences, University of Concepcion, Concepcion, Chile
| | - Julio Villena
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan. .,Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), San Miguel de Tucuman, Tucuman, Argentina.
| | - Haruki Kitazawa
- Food and Feed Immunology Group, Graduate School of Agricultural Science, Tohoku University, Sendai, 981-8555, Japan. .,Livestock Immunology Unit, International Education and Research Center for Food Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
| |
Collapse
|
|
39
|
Morgan RL, Preidis GA, Kashyap PC, Weizman AV, Sadeghirad B. Probiotics Reduce Mortality and Morbidity in Preterm, Low-Birth-Weight Infants: A Systematic Review and Network Meta-analysis of Randomized Trials. Gastroenterology 2020; 159:467-480. [PMID: 32592699 PMCID: PMC8014956 DOI: 10.1053/j.gastro.2020.05.096] [Citation(s) in RCA: 111] [Impact Index Per Article: 22.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 05/07/2020] [Accepted: 05/21/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND & AIMS We aimed to compare the effectiveness of single- vs multiple-strain probiotics in a network meta-analysis of randomized trials. METHODS We searched MEDLINE, Embase, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, BIOSIS Previews, and Google Scholar through January 1, 2019, for studies of single-strain and multistrain probiotic formulations on the outcomes of preterm, low-birth-weight neonates. We used a frequentist approach for network meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence. Primary outcomes included all-cause mortality, severe necrotizing enterocolitis (NEC) (Bell stage II or more), and culture-proven sepsis. RESULTS We analyzed data from 63 trials involving 15,712 preterm infants. Compared with placebo, a combination of 1 or more Lactobacillus species (spp) and 1 or more Bifidobacterium spp was the only intervention with moderate- or high-quality evidence of reduced all-cause mortality (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.39-0.80). Among interventions with moderate- or high-quality evidence for efficacy compared with placebo, combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp, Bifidobacterium animalis subspecies lactis, Lactobacillus reuteri, or Lactobacillus rhamnosus significantly reduced severe NEC (OR, 0.35 [95% CI, 0.20-0.59]; OR, 0.31 [95% CI, 0.13-0.74]; OR, 0.55 [95% CI, 0.34-0.91]; and OR, 0.44 [95% CI, 0.21-0.90], respectively). There was moderate- or high-quality evidence that combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp and Saccharomyces boulardii reduced the number of days to reach full feeding (mean reduction of 3.30 days [95% CI, reduction of 5.91-0.69 days]). There was moderate- or high-quality evidence that, compared with placebo, the single-species product B animalis subsp lactis or L reuteri significantly reduced duration of hospitalization (mean reduction of 13.00 days [95% CI, reduction of 22.71-3.29 days] and mean reduction of 7.89 days [95% CI, reduction of 11.60-4.17 days], respectively). CONCLUSIONS In a systematic review and network meta-analysis of studies to determine the effects of single-strain and multistrain probiotic formulations on outcomes of preterm, low-birth-weight neonates, we found moderate to high evidence for the superiority of combinations of 1 or more Lactobacillus spp and 1 or more Bifidobacterium spp vs single- and other multiple-strain probiotic treatments. The combinations of Bacillus spp and Enterococcus spp, and 1 or more Bifidobacterium spp and Streptococcus salivarius subsp thermophilus, might produce the largest reduction in NEC development. Further trials are needed.
Collapse
Affiliation(s)
- Rebecca L. Morgan
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Geoffrey A. Preidis
- Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas
| | - Purna C. Kashyap
- Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Adam V. Weizman
- Division of Gastroenterology, Mount Sinai Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Behnam Sadeghirad
- Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Anesthesia, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada; The Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada.
| | | |
Collapse
|
|
40
|
Preidis GA, Weizman AV, Kashyap PC, Morgan RL. AGA Technical Review on the Role of Probiotics in the Management of Gastrointestinal Disorders. Gastroenterology 2020; 159:708-738.e4. [PMID: 32531292 PMCID: PMC8018518 DOI: 10.1053/j.gastro.2020.05.060] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Geoffrey A. Preidis
- Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas
| | - Adam V. Weizman
- Division of Gastroenterology, Mount Sinai Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Purna C. Kashyap
- Enteric Neuroscience Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Rebecca L. Morgan
- Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| |
Collapse
|
|
41
|
Jiao X, Fu MD, Wang YY, Xue J, Zhang Y. Bifidobacterium and Lactobacillus for preventing necrotizing enterocolitis in very-low-birth-weight preterm infants: a systematic review and meta-analysis. World J Pediatr 2020; 16:135-142. [PMID: 31482480 DOI: 10.1007/s12519-019-00297-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 07/18/2019] [Indexed: 01/12/2023]
Abstract
BACKGROUND The therapeutic effect of Bifidobacterium and Lactobacillus on necrotizing enterocolitis (NEC) in very-low-birth-weight preterm infants was controversial, and we aimed to explore the exact impact of the two probiotics. METHODS The PubMed, EMBASE, Web of Science and Cochrane Library were systematically searched for studies published from January 1, 2010 to February 28, 2019. Results were combined with fixed-effect model or random-effect model with specific conditions. Sensitivity analysis was conducted by the trim-and-fill method, and the Begger's and Egger's test were used to measure publication bias. RESULTS The meta-analysis included 16 original articles with 4632 very-low-birth-weight preterm infants. With respect to the intervention of Bifidobacterium, we estimated non-significant decrease in the morbidity of NEC with a risk ratio (RR) of 0.75 [95% confidence internal (CI) 0.56-1.01, P = 0.06]. Regarding the effect of Lactobacillus, there was no evidence of significant lower risk in the incidence of NEC (RR = 0.67, 95% CI 0.39-1.17, P = 0.16). The use of mixture of probiotics (Bifidobacterium and Lactobacillus) reduced the risk of NEC in the probiotics group (RR = 0.45, 95% CI 0.25-0.80, P = 0.007). CONCLUSION The mixture of Bifidobacterium and Lactobacillus could prevent the morbidity of NEC in very-low-birth-weight preterm infants. But Bifidobacterium or Lactobacillus alone did not show this effect.
Collapse
Affiliation(s)
- Xue Jiao
- School of Medicine, Shandong University, Jinan, China
| | - Meng-Di Fu
- School of Medicine, Shandong University, Jinan, China
| | - Ya-Yun Wang
- Department of Neonatology, Second Hospital of Shandong University, 247# Beiyuan Road, Jinan, China
| | - Jiang Xue
- Department of Neonatology, Second Hospital of Shandong University, 247# Beiyuan Road, Jinan, China
| | - Yuan Zhang
- Center of Evidence-Based Medicine, Institute of Medical Sciences, Second Hospital of Shandong University, 247# Beiyuan Road, Jinan, China. .,School of Public Health, Shandong University, Jinan, China.
| |
Collapse
|
|
42
|
Safety and efficacy of Lactobacillus for preventing necrotizing enterocolitis in preterm infants. Int J Surg 2020; 76:79-87. [PMID: 32109650 DOI: 10.1016/j.ijsu.2020.02.031] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 02/14/2020] [Accepted: 02/19/2020] [Indexed: 12/17/2022]
Abstract
AIM To evaluate the safety and efficacy of Lactobacillus for preventing necrotizing enterocolitis (NEC) in preterm infants. METHODS We searched the Cochrane Library, PubMed, EMBASE, and Web of Science databases from inception to September 2019. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to compare outcomes. We also performed a subgroup analysis of the incidence of NEC. Moreover, a sensitivity analysis was performed to examine the stability of the results. A Begg funnel plot was generated to detect publication bias. Two reviewers assessed trial quality and extracted data independently. This work has been reported in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement and the Assessing the Methodological Quality of Systematic Reviews guidelines. Statistical analysis was performed using standard procedures in Review Manager 5.2 software. RESULTS Twenty-three randomized, placebo-controlled studies (N = 4686 participants) were included in this analysis. Comparing the Lactobacillus and control groups, a significant reduction was found in the incidence of NEC (RR 0.34, 95% CI 0.25-0.46; P < 0.00001) and death (RR 0.48, 95% CI 0.36-0.64; P < 0.00001). No significant difference in the incidence of sepsis was found between the Lactobacillus and placebo groups (RR 0.90, 95% CI 0.72-1.12; P = 0.34). CONCLUSIONS Lactobacillus is safe and can prevent necrotizing enterocolitis in preterm infants.
Collapse
|
|
43
|
Strunk T, Hibbert JE, Doherty D, Nathan E, Simmer K, Patole SK, Trend S, Richmond P, Burgner D, Currie A. Lactoferrin Expression Is Not Associated with Late-Onset Sepsis in Very Preterm Infants. Neonatology 2020; 117:606-611. [PMID: 32862184 DOI: 10.1159/000509404] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Accepted: 06/15/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND Preterm infants are at a high risk of developing late-onset sepsis (LOS). Lactoferrin is one of the most abundant endogenous antimicrobial proteins expressed in breast milk, stools, and blood, and a candidate for preventive intervention. Large clinical trials have recently investigated whether enteral supplementation with bovine lactoferrin reduces LOS. AIM To characterize lactoferrin levels in preterm infants with and without LOS during the first month of life. METHODS Very preterm and term infants were recruited and serial biosamples collected during the first month of life. Lactoferrin levels were determined by immunoassay in cord blood and peripheral blood on days 1, 7, 14, 21, and 28; in the stools on days 1 and 28; and in the mother's breast milk on days 7 and 21. Furthermore, we assessed the capacity of the peripheral blood to release lactoferrin in response to an in vitro challenge with live Staphylococcus epidermidis, lipopolysaccharide, and fibroblast-stimulating lipopeptide 1. RESULTS Plasma lactoferrin levels were higher in cord blood and day 1 peripheral blood and declined during the first month of life. Plasma lactoferrin levels were similar in term infants and in preterm infants with (n = 32) and without LOS (n = 53). S. epidermidis-induced lactoferrin levels were lower following the sepsis episode. CONCLUSIONS Endogenous lactoferrin expression in preterm infants does not appear to affect their risk of developing LOS. These findings are in line with the lack of benefit recently observed in large trials of enteral supplementation with bovine lactoferrin to prevent LOS.
Collapse
Affiliation(s)
- Tobias Strunk
- Neonatal Directorate, King Edward Memorial Hospital, Perth, Washington, Australia, .,Wesfarmers' Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Washington, Australia, .,School of Medicine, University of Western Australia, Perth, Washington, Australia,
| | - Julie Elizabeth Hibbert
- Wesfarmers' Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Washington, Australia.,School of Medicine, University of Western Australia, Perth, Washington, Australia
| | - Dorota Doherty
- School of Medicine, University of Western Australia, Perth, Washington, Australia
| | - Elizabeth Nathan
- School of Medicine, University of Western Australia, Perth, Washington, Australia
| | - Karen Simmer
- Neonatal Directorate, King Edward Memorial Hospital, Perth, Washington, Australia.,Wesfarmers' Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Washington, Australia.,School of Medicine, University of Western Australia, Perth, Washington, Australia
| | - Sanjay Keshav Patole
- Neonatal Directorate, King Edward Memorial Hospital, Perth, Washington, Australia.,School of Medicine, University of Western Australia, Perth, Washington, Australia
| | - Stephanie Trend
- Wesfarmers' Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Washington, Australia.,Centre for Neuromuscular and Neurological Disorders, Perron Institute for Neurological and Translational Science, University of Western Australia, Perth, Washington, Australia
| | - Peter Richmond
- Wesfarmers' Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Washington, Australia.,School of Medicine, University of Western Australia, Perth, Washington, Australia.,Department of Immunology, Perth Children's Hospital, Perth, Washington, Australia
| | - David Burgner
- Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
| | - Andrew Currie
- Wesfarmers' Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Washington, Australia.,Medical, Molecular and Forensic Sciences, Murdoch University, Perth, Washington, Australia
| |
Collapse
|
|
44
|
Senizza A, Callegari ML, Senizza B, Minuti A, Rocchetti G, Morelli L, Patrone V. Effects of Linoleic Acid on Gut-Derived Bifidobacterium breve DSM 20213: A Transcriptomic Approach. Microorganisms 2019; 7:microorganisms7120710. [PMID: 31861103 PMCID: PMC6955684 DOI: 10.3390/microorganisms7120710] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Revised: 11/12/2019] [Accepted: 12/16/2019] [Indexed: 02/08/2023] Open
Abstract
Bacterial production of conjugated linoleic acid (CLA) has recently received great attention because of the potential health benefits of this fatty acid. Linoleic acid (LA) can be converted to CLA by several microorganisms, including bifidobacteria, possibly as a detoxification mechanism to avoid the growth inhibition effect of LA. In the present in vitro study, we investigated the gene expression landscape of the intestinal strain Bifidobacterium breve DSM 20213 when exposed to LA. Transcriptomic analysis using RNA-seq revealed that LA induced a multifactorial stress response in the test strain, including upregulation of genes involved in iron uptake and downregulation of genes involved in sugar and oligopeptide transport. We also observed reduced transcription of genes involved in membrane and pili biosynthesis. The upregulation of iron uptake was not related to any putative ability of LA to chelate Fe2+, but was somewhat linked to stress response. Furthermore, we demonstrated that LA increased reactive oxygen species (ROS) production in bacterial cells, activating an oxidative stress response. This response was proved by thioredoxin reductase transcription, and was primarily evident among bacteria cultured in the absence of cysteine. This is the first report of the potential mechanisms involved in bacterial LA transport and stress response in B. breve.
Collapse
Affiliation(s)
- Alice Senizza
- Department for Sustainable Food Process (DiSTAS), Università Cattolica del Sacro Cuore, via Emilia Parmense 84, 29122 Piacenza, Italy; (A.S.); (M.L.C.); (B.S.); (G.R.); (L.M.)
| | - Maria Luisa Callegari
- Department for Sustainable Food Process (DiSTAS), Università Cattolica del Sacro Cuore, via Emilia Parmense 84, 29122 Piacenza, Italy; (A.S.); (M.L.C.); (B.S.); (G.R.); (L.M.)
- Biotechnology Research Centre (CRB), via Milano 24, 26100 Cremona, Italy
| | - Biancamaria Senizza
- Department for Sustainable Food Process (DiSTAS), Università Cattolica del Sacro Cuore, via Emilia Parmense 84, 29122 Piacenza, Italy; (A.S.); (M.L.C.); (B.S.); (G.R.); (L.M.)
| | - Andrea Minuti
- Department of Animal Science, Food and Nutrition (DiANA), Università Cattolica del Sacro Cuore, via Emilia Parmense 84, 29122 Piacenza, Italy;
- Nutrigenomics and Proteomics Research Center (PRONUTRIGEN), Università Cattolica del Sacro Cuore, via Emilia Parmense 84, 29122 Piacenza, Italy
| | - Gabriele Rocchetti
- Department for Sustainable Food Process (DiSTAS), Università Cattolica del Sacro Cuore, via Emilia Parmense 84, 29122 Piacenza, Italy; (A.S.); (M.L.C.); (B.S.); (G.R.); (L.M.)
| | - Lorenzo Morelli
- Department for Sustainable Food Process (DiSTAS), Università Cattolica del Sacro Cuore, via Emilia Parmense 84, 29122 Piacenza, Italy; (A.S.); (M.L.C.); (B.S.); (G.R.); (L.M.)
- Biotechnology Research Centre (CRB), via Milano 24, 26100 Cremona, Italy
| | - Vania Patrone
- Department for Sustainable Food Process (DiSTAS), Università Cattolica del Sacro Cuore, via Emilia Parmense 84, 29122 Piacenza, Italy; (A.S.); (M.L.C.); (B.S.); (G.R.); (L.M.)
- Nutrigenomics and Proteomics Research Center (PRONUTRIGEN), Università Cattolica del Sacro Cuore, via Emilia Parmense 84, 29122 Piacenza, Italy
- Correspondence: ; Tel.: +39-0523-599247
| |
Collapse
|
|
45
|
Jiang T, Zhang H, Xu X, Li H, Yang J. Mixed probiotics decrease the incidence of stage II-III necrotizing enterocolitis and death: A systematic review and meta-analysis. Microb Pathog 2019; 138:103794. [PMID: 31672528 DOI: 10.1016/j.micpath.2019.103794] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2019] [Revised: 09/24/2019] [Accepted: 10/08/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in premature infants. In order to evaluate the efficacy of probiotics in the prevention of stage II-III NEC, we performed a meta-analysis of clinical studies. METHODS We searched in PubMed, Medline and Embase from 1 January 1990 to 16 January 2018. Heterogeneity was examined by Q-test. Publication bias was evaluated by funnel plot and Egger's regression test. RESULTS 30 articles were identified meeting the inclusion criteria. Data showed that probiotics supplement could significantly reduce the risk of stage II-III NEC (RR = 0.51, 95% CI, 0.38 to 0.67, P < 0.001) and death rate (RR = 0.69, 95% CI, 0.55 to 0.87, P = 0.002). The mixed probiotics and lactobacillus could reduce the risk of stage II-III NEC (for mixed probiotics, RR = 0.39, 95% CI, 0.26 to 0.57; for lactobacillus, RR = 0.53, 95% CI, 0.36 to 0.78), while bifidobacterium or saccharomyces did not have such effect. The results also indicated that only the mixed probiotics could reduce the risk of deaths (RR = 0.52, 95%CI, 0.34 to 0.80). Subgroup analysis for mortality revealed that probiotics had significant effect in Asian region (RR = 0.54, 95% CI, 0.37 to 0.80, P = 0.002) but not in non-Asian region (RR = 0.84, 95% CI, 0.66 to 1.08, P = 0.179). CONCLUSIONS Probiotics could significantly decrease the risk of stage II-III NEC and death. Compared to using single probiotics species, the application of combining different probiotics has a better efficacy in the prevention of stage II-III NEC and death, especially in the Asian population.
Collapse
Affiliation(s)
- Tianliang Jiang
- Department of Prevention Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China
| | - Huai Zhang
- Department of Prevention Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China
| | - Xianrong Xu
- Department of Prevention Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China
| | - Hongjuan Li
- Department of Basic Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China
| | - Jun Yang
- Department of Prevention Medicine, School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
| |
Collapse
|
|
46
|
Probiotic strategies to prevent necrotizing enterocolitis in preterm infants: a meta-analysis. Pediatr Surg Int 2019; 35:1143-1162. [PMID: 31420743 DOI: 10.1007/s00383-019-04547-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/09/2019] [Indexed: 12/30/2022]
Abstract
PURPOSE We aimed to compare probiotics with placebo for necrotizing enterocolitis in preterm infants and to evaluate the safety and effect and strict effect of specific probiotic genera. METHODS Data recorded until January 2019 were searched, and relevant academic articles from PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were selected by two independent reviewers. Two reviewers independently included randomized controlled trials that compared probiotics and placebo in preterm infants. The outcomes included more than one of the following outcomes: incidence of necrotizing enterocolitis, necrotizing enterocolitis-related mortality, incidence of sepsis, and all-cause mortality. Two reviewers independently extracted data and assessed the risk of bias and quality of evidence. RESULTS We identified 34 eligible studies of 9161 participants. This meta-analysis showed an overall advantage of probiotics to prevent the incidence of necrotizing enterocolitis (3.54%) and gut-associated sepsis (15.59%), and decrease mortality (5.23%) in preterm infants. A probiotic mixture showed a huge advantage and vitality in preventing necrotizing enterocolitis (2.48%) and gut-associated sepsis (18.39%), and in reducing mortality (5.57%) in preterm infants. CONCLUSION The probiotic mixture showed advantages over the single strains to decrease the incidences of necrotizing enterocolitis and gut-associated sepsis, and mortality in preterm infants.
Collapse
|
|
47
|
Bi LW, Yan BL, Yang QY, Li MM, Cui HL. Which is the best probiotic treatment strategy to prevent the necrotizing enterocolitis in premature infants: A network meta-analysis revealing the efficacy and safety. Medicine (Baltimore) 2019; 98:e17521. [PMID: 31593123 PMCID: PMC6799420 DOI: 10.1097/md.0000000000017521] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Previous studies have neglected to report the specific action of different probiotic genera in preterm infants. To evaluate the efficacy and safety of specific probiotic genera, we performed a network meta-analysis (NMA) to identify the best prevention strategy for necrotizing enterocolitis in preterm infants. METHODS MEDLINE, PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials had been searched for randomized control trials reporting the probiotics strategy for premature infants. RESULTS We identified 34 eligible studies of 9161 participants. The intervention in the observation group was to add probiotics for feeding: Lactobacilli in 6 studies; Bifidobacterium in 8 studies; Bacillus in 1 study; Saccharomyces in 4 studies and probiotic mixture in 15 studies. This NMA showed a significant advantage of probiotic mixture and Bifidobacterium to prevent the incidence of necrotizing enterocolitis in preterm infants. A probiotic mixture showed effectiveness in reducing mortality in preterm infants. CONCLUSION The recent literature has reported a total of 5 probiotic strategies, including Bacillus, Bifidobacterium, Lactobacillus, Saccharomyces, and probiotic mixture. Our thorough review and NMA provided a piece of available evidence to choose optimal probiotics prophylactic strategy for premature infants. The results indicated that probiotic mixture and Bifidobacterium showed a stronger advantage to use in preterm infants; the other probiotic genera failed to show an obvious effect to reduce the incidence of NEC, sepsis and all-cause death. More trials need to be performed to determine the optimal probiotic treatment strategy to prevent preterm related complications.
Collapse
Affiliation(s)
- Le-wee Bi
- Department of the Graduate School, Tianjin Medical University
| | - Bei-lei Yan
- Department of the Graduate School, Tianjin Medical University
| | - Qian-yu Yang
- Department of the Graduate School, Tianjin Medical University
| | - Miao-miao Li
- Department of General Surgery, Tianjin Children's Hospital, Tianjin, China
| | - Hua-lei Cui
- Department of General Surgery, Tianjin Children's Hospital, Tianjin, China
| |
Collapse
|
|
48
|
Prado C, Michels M, Ávila P, Burger H, Milioli MVM, Dal-Pizzol F. The protective effects of fecal microbiota transplantation in an experimental model of necrotizing enterocolitis. J Pediatr Surg 2019; 54:1578-1583. [PMID: 30414693 DOI: 10.1016/j.jpedsurg.2018.10.045] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 09/24/2018] [Accepted: 10/01/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND Necrotizing enterocolitis (NEC) is a serious disease that affects premature neonates, causing high mortality. In the search for new options of treatment it was investigated whether fecal microbiota transplantation (FMT) decreased the inflammatory response during NEC development in experimental model. METHODS Wistar rats were used and divided as follows: naïve, control (NEC induction), FMT-before (transplantation of microbiota before insult) and FMT-after (microbiota transplantation after insult). The microbiota transplantation was performed by administering a feces solution obtained from an adult donor rat. The induction of enterocolitis involves feeding by artificial formula, hypothermia, hypoxia and endotoxin administration. MPO activity, TNF-α, IL-1β and IL-6 levels, oxidative and nitrosative damage and the grade of intestinal mucosa lesion were analyzed. RESULTS The control group had a significant increase of inflammatory and oxidative parameters when compared to naive animals. Both FMT-before and after decreased all inflammatory and oxidative damage parameters when compared to control group. This was also true to the intestinal mucosa damage. CONCLUSION FMT administered just before or after NEC induction improved gut and systemic inflammation, and gut oxidative damage and intestinal injury.
Collapse
Affiliation(s)
- Christian Prado
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| | - Monique Michels
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil.
| | - Pricila Ávila
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| | - Henrique Burger
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| | - Maria Vitória Meller Milioli
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| | - Felipe Dal-Pizzol
- Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil
| |
Collapse
|
|
49
|
Wong CB, Iwabuchi N, Xiao JZ. Exploring the Science behind Bifidobacterium breve M-16V in Infant Health. Nutrients 2019; 11:nu11081724. [PMID: 31349739 PMCID: PMC6723912 DOI: 10.3390/nu11081724] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Revised: 07/22/2019] [Accepted: 07/24/2019] [Indexed: 12/18/2022] Open
Abstract
Probiotics intervention has been proposed as a feasible preventative approach against adverse health-related complications in infants. Nevertheless, the umbrella concept of probiotics has led to a massive application of probiotics in a range of products for promoting infant health, for which the strain-specificity, safety and efficacy findings associated with a specific probiotics strain are not clearly defined. Bifidobacterium breve M-16V is a commonly used probiotic strain in infants. M-16V has been demonstrated to offer potential in protecting infants from developing the devastating necrotising enterocolitis (NEC) and allergic diseases. This review comprehends the potential beneficial effects of M-16V on infant health particularly in the prevention and treatment of premature birth complications and immune-mediated disorders in infants. Mechanistic studies supporting the use of M-16V implicated that M-16V is capable of promoting early gut microbial colonisation and may be involved in the regulation of immune balance and inflammatory response to protect high-risk infants from NEC and allergies. Summarised information on M-16V has provided conceptual proof of the use of M-16V as a potential probiotics candidate aimed at promoting infant health, particularly in the vulnerable preterm population.
Collapse
MESH Headings
- Animals
- Animals, Newborn
- Bifidobacterium breve/physiology
- Disease Models, Animal
- Gastrointestinal Microbiome
- Gestational Age
- Humans
- Infant
- Infant Health
- Infant, Newborn
- Infant, Newborn, Diseases/diagnosis
- Infant, Newborn, Diseases/microbiology
- Infant, Newborn, Diseases/prevention & control
- Infant, Premature
- Probiotics/adverse effects
- Probiotics/therapeutic use
Collapse
Affiliation(s)
- Chyn Boon Wong
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa 252-8583, Japan
| | - Noriyuki Iwabuchi
- Food Ingredients and Technology Institute, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa 252-8583, Japan
| | - Jin-Zhong Xiao
- Next Generation Science Institute, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa 252-8583, Japan.
| |
Collapse
|
|
50
|
Tarhani F, Nezami A. Role of probiotics in treatment of congenital heart disease and necrotizing enterocolitis. PHARMANUTRITION 2019. [DOI: 10.1016/j.phanu.2019.100144] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
|