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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.
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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
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Inchingolo F, Inchingolo AM, Latini G, Ferrante L, de Ruvo E, Campanelli M, Longo M, Palermo A, Inchingolo AD, Dipalma G. Difference in the Intestinal Microbiota between Breastfeed Infants and Infants Fed with Artificial Milk: A Systematic Review. Pathogens 2024; 13:533. [PMID: 39057760 PMCID: PMC11280328 DOI: 10.3390/pathogens13070533] [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: 05/29/2024] [Revised: 06/18/2024] [Accepted: 06/20/2024] [Indexed: 07/28/2024] Open
Abstract
The gut microbiota (GM) plays a crucial role in human health, particularly during the first years of life. Differences in GM between breastfed and formula (F)-fed infants may influence long-term health outcomes. This systematic review aims to compare the gut microbiota of breastfed infants with that of F-fed infants and to evaluate the clinical implications of these differences. We searched databases on Scopus, Web of Science, and Pubmed with the following keywords: "gut microbiota", "gut microbiome", and "neonatal milk". The inclusion criteria were articles relating to the analysis of the intestinal microbiome of newborns in relation to the type of nutrition, clinical studies or case series, excluding reviews, meta-analyses, animal models, and in vitro studies. The screening phase ended with the selection of 13 publications for this work. Breastfed infants showed higher levels of beneficial bacteria such as Bifidobacterium and Lactobacillus, while F-fed infants had a higher prevalence of potentially pathogenic bacteria, including Clostridium difficile and Enterobacteriaceae. Infant feeding type influences the composition of oral GM significantly. Breastfeeding promotes a healthier and more diverse microbial ecosystem, which may offer protective health benefits. Future research should explore strategies to improve the GM of F-fed infants and understand the long-term health implications.
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Affiliation(s)
- Francesco Inchingolo
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy or (A.M.I.); or (G.L.); or (L.F.); or (E.d.R.); (M.L.); or (A.D.I.); or (G.D.)
| | - Angelo Michele Inchingolo
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy or (A.M.I.); or (G.L.); or (L.F.); or (E.d.R.); (M.L.); or (A.D.I.); or (G.D.)
| | - Giulia Latini
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy or (A.M.I.); or (G.L.); or (L.F.); or (E.d.R.); (M.L.); or (A.D.I.); or (G.D.)
| | - Laura Ferrante
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy or (A.M.I.); or (G.L.); or (L.F.); or (E.d.R.); (M.L.); or (A.D.I.); or (G.D.)
| | - Elisabetta de Ruvo
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy or (A.M.I.); or (G.L.); or (L.F.); or (E.d.R.); (M.L.); or (A.D.I.); or (G.D.)
| | - Merigrazia Campanelli
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy or (A.M.I.); or (G.L.); or (L.F.); or (E.d.R.); (M.L.); or (A.D.I.); or (G.D.)
| | - Marialuisa Longo
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy or (A.M.I.); or (G.L.); or (L.F.); or (E.d.R.); (M.L.); or (A.D.I.); or (G.D.)
| | - Andrea Palermo
- College of Medicine and Dentistry, Birmingham B4 6BN, UK;
| | - Alessio Danilo Inchingolo
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy or (A.M.I.); or (G.L.); or (L.F.); or (E.d.R.); (M.L.); or (A.D.I.); or (G.D.)
| | - Gianna Dipalma
- Interdisciplinary Department of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy or (A.M.I.); or (G.L.); or (L.F.); or (E.d.R.); (M.L.); or (A.D.I.); or (G.D.)
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Wang Y, Florez ID, Morgan RL, Foroutan F, Chang Y, Crandon HN, Zeraatkar D, Bala MM, Mao RQ, Tao B, Shahid S, Wang X, Beyene J, Offringa M, Sherman PM, El Gouhary E, Guyatt GH, Sadeghirad B. Probiotics, Prebiotics, Lactoferrin, and Combination Products for Prevention of Mortality and Morbidity in Preterm Infants: A Systematic Review and Network Meta-Analysis. JAMA Pediatr 2023; 177:1158-1167. [PMID: 37782505 PMCID: PMC10546299 DOI: 10.1001/jamapediatrics.2023.3849] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 08/01/2023] [Indexed: 10/03/2023]
Abstract
Importance Modulation of intestinal microbiome by administering probiotics, prebiotics, or both may prevent morbidity and mortality in premature infants. Objective To assess the comparative effectiveness of alternative prophylactic strategies through a network meta-analysis (NMA) of randomized clinical trials. Data Sources MEDLINE, EMBASE, Science Citation Index Expanded, CINAHL, Scopus, Cochrane CENTRAL, and Google Scholar from inception until May 10, 2023. Study Selection Eligible trials tested probiotics, prebiotics, lactoferrin, and combination products for prevention of morbidity or mortality in preterm infants. Data Extraction and Synthesis A frequentist random-effects model was used for the NMA, and the certainty of evidence and inferences regarding relative effectiveness were assessed using the GRADE approach. Main Outcomes and Measures All-cause mortality, severe necrotizing enterocolitis, culture-proven sepsis, feeding intolerance, time to reach full enteral feeding, and duration of hospitalization. Results A total of 106 trials involving 25 840 preterm infants were included. Only multiple-strain probiotics were associated with reduced all-cause mortality compared with placebo (risk ratio [RR], 0.69; 95% CI, 0.56 to 0.86; risk difference [RD], -1.7%; 95% CI, -2.4% to -0.8%). Multiple-strain probiotics alone (vs placebo: RR, 0.38; 95% CI, 0.30 to 0.50; RD, -3.7%; 95% CI, -4.1% to -2.9%) or in combination with oligosaccharides (vs placebo: RR, 0.13; 95% CI, 0.05 to 0.37; RD, -5.1%; 95% CI, -5.6% to -3.7%) were among the most effective interventions reducing severe necrotizing enterocolitis. Single-strain probiotics in combination with lactoferrin (vs placebo RR, 0.33; 95% CI, 0.14 to 0.78; RD, -10.7%; 95% CI, -13.7% to -3.5%) were the most effective intervention for reducing sepsis. Multiple-strain probiotics alone (RR, 0.61; 95% CI, 0.46 to 0.80; RD, -10.0%; 95% CI, -13.9% to -5.1%) or in combination with oligosaccharides (RR, 0.45; 95% CI, 0.29 to 0.67; RD, -14.1%; 95% CI, -18.3% to -8.5%) and single-strain probiotics (RR, 0.61; 95% CI, 0.51 to 0.72; RD, -10.0%; 95% CI, -12.6% to -7.2%) proved of best effectiveness in reduction of feeding intolerance vs placebo. Single-strain probiotics (MD, -1.94 days; 95% CI, -2.96 to -0.92) and multistrain probiotics (MD, -2.03 days; 95% CI, -3.04 to -1.02) proved the most effective in reducing the time to reach full enteral feeding compared with placebo. Only single-strain and multistrain probiotics were associated with greater effectiveness compared with placebo in reducing duration of hospitalization (MD, -3.31 days; 95% CI, -5.05 to -1.58; and MD, -2.20 days; 95% CI, -4.08 to -0.31, respectively). Conclusions and Relevance In this systematic review and NMA, moderate- to high-certainty evidence demonstrated an association between multistrain probiotics and reduction in all-cause mortality; these interventions were also associated with the best effectiveness for other key outcomes. Combination products, including single- and multiple-strain probiotics combined with prebiotics or lactoferrin, were associated with the largest reduction in morbidity and mortality.
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Affiliation(s)
- Yuting Wang
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
| | - Ivan D. Florez
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
- Department of Pediatrics, University of Antioquia, Medellin, Colombia
- Pediatric Intensive Care Unit, Clínica Las Americas-AUNA, Medellin, Colombia
| | - Rebecca L. Morgan
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
- School of Medicine, Case Western Reserve University, Cleveland, Ohio
| | - Farid Foroutan
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
- Ted Rogers Centre for Heart Research, University Health Network, Toronto, Ontario, Canada
| | - Yaping Chang
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
| | - Holly N. Crandon
- Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada
| | - Dena Zeraatkar
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
- Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada
| | - Malgorzata M. Bala
- Department of Hygiene and Dietetics, Jagiellonian University Medical College, Krakow, Poland
| | - Randi Q. Mao
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Brendan Tao
- Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
| | - Shaneela Shahid
- Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
| | - Xiaoqin Wang
- Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada
| | - Joseph Beyene
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
| | - Martin Offringa
- Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
| | - Philip M. Sherman
- Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Enas El Gouhary
- Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
| | - Gordon H. Guyatt
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
| | - Behnam Sadeghirad
- Department of Health Research Methods, Evidence, and Impact (HEI), McMaster University, Hamilton, Ontario, Canada
- Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Ontario, Canada
- Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada
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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.
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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
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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
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Wang Y, Hang C, Hu J, Li C, Zhan C, Pan J, Yuan T. Role of gut-brain axis in neurodevelopmental impairment of necrotizing enterocolitis. Front Neurosci 2023; 17:1059552. [PMID: 36743802 PMCID: PMC9894661 DOI: 10.3389/fnins.2023.1059552] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Accepted: 01/02/2023] [Indexed: 01/20/2023] Open
Abstract
Necrotizing enterocolitis (NEC) is a common gastrointestinal disease of preterm infants with high morbidity and mortality. In survivors of NEC, one of the leading causes of long-term morbidity is the development of severe neurocognitive injury. The exact pathogenesis of neurodevelopmental delay in NEC remains unknown, but microbiota is considered to have dramatic effects on the development and function of the host brain via the gut-brain axis. In this review, we discuss the characteristics of microbiota of NEC, the impaired neurological outcomes, and the role of the complex interplay between the intestinal microbiota and brain to influence neurodevelopment in NEC. The increasing knowledge of microbial-host interactions has the potential to generate novel therapies for manipulating brain development in the future.
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Affiliation(s)
- Yu Wang
- Department of Neonatology, Children’s Hospital of Zhejiang University, Hangzhou, China
| | - Chengcheng Hang
- Department of Neonatology, Children’s Hospital of Zhejiang University, Hangzhou, China
| | - Jun Hu
- Department of Surgical Intensive Care Unit, Second Affiliated Hospital of Zhejiang University, Hangzhou, China
| | - Chen Li
- Department of Neonatology, Children’s Hospital of Zhejiang University, Hangzhou, China
| | - Canyang Zhan
- Department of Neonatology, Children’s Hospital of Zhejiang University, Hangzhou, China
| | - Jiarong Pan
- Department of Neonatology, Children’s Hospital of Zhejiang University, Hangzhou, China
| | - Tianming Yuan
- Department of Neonatology, Children’s Hospital of Zhejiang University, Hangzhou, China,*Correspondence: Tianming Yuan,
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Mercer EM, Arrieta MC. Probiotics to improve the gut microbiome in premature infants: are we there yet? Gut Microbes 2023; 15:2201160. [PMID: 37122152 PMCID: PMC10153018 DOI: 10.1080/19490976.2023.2201160] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 04/06/2023] [Indexed: 05/02/2023] Open
Abstract
Gut microbiome maturation in infants born prematurely is uniquely influenced by the physiological, clinical, and environmental factors surrounding preterm birth and early life, leading to altered patterns of microbial succession relative to term infants during the first months of life. These differences in microbiome composition are implicated in acute clinical conditions that disproportionately affect preterm infants, including necrotizing enterocolitis (NEC) and late-onset sepsis (LOS). Probiotic supplementation initiated early in life is an effective prophylactic measure for preventing NEC, LOS, and other clinical concerns relevant to preterm infants. In parallel, reported benefits of probiotics on the preterm gut microbiome, metabolome, and immune function are beginning to emerge. This review summarizes the current literature on the influence of probiotics on the gut microbiome of preterm infants, outlines potential mechanisms by which these effects are exerted, and highlights important clinical considerations for determining the best practices for probiotic use in premature infants.
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Affiliation(s)
- Emily M. Mercer
- Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
- Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada
- International Microbiome Center, University of Calgary, Calgary, Alberta, Canada
| | - Marie-Claire Arrieta
- Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada
- Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada
- International Microbiome Center, University of Calgary, Calgary, Alberta, Canada
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Zeber-Lubecka N, Kulecka M, Lindner B, Krynicki R, Paziewska A, Nowakowski A, Bidzinski M, Ostrowski J. Increased diversity of a cervical microbiome associates with cervical cancer. Front Oncol 2022; 12:1005537. [PMID: 36249017 PMCID: PMC9562559 DOI: 10.3389/fonc.2022.1005537] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 09/05/2022] [Indexed: 12/02/2022] Open
Abstract
The cervical microbiome (CM) is a complex ecosystem that can change in response to gynecological cancers. We aimed to evaluate changes in the CM of patients who underwent chemoradiation (CRT) therapy for locally advanced cervical cancer. Before and after CRT, cervical swab samples were collected from 16 patients with squamous cell carcinoma of the cervix, and 30 healthy women. All samples were subjected to 16s rRNA-Seq analysis. In healthy premenopausal women the CM comprised mostly Lactobacillus (>90%); the CM community in samples from both pre- and postmenopausal pre-treatment cancer patients was heterogeneous, with a low proportion of Lactobacillus in younger cases. On the genus level, 27 and 11 taxa differentiated healthy controls from cancer patients in pre- and postmenopausal age groups, while 31 and 2 genera differentiated pre- and post-radiation samples and pre-radiation and the follow-up samples, respectively. Microbiome diversity was significantly higher in pre-treatment patients than in healthy controls. The results reveal significant alterations in the CM of cervical cancer patients relative to that in healthy controls; these changes were more striking after CRT. However, further research is needed to determine whether alteration of the CM offers new therapeutic options.
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Affiliation(s)
- Natalia Zeber-Lubecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Maria Kulecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Bogusław Lindner
- Department of Gynaecological Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Ryszard Krynicki
- Department of Gynaecological Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Agnieszka Paziewska
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Andrzej Nowakowski
- Department of Cancer Prevention, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Mariusz Bidzinski
- Department of Gynaecological Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Jerzy Ostrowski
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
- *Correspondence: Jerzy Ostrowski,
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The Combination of Intestinal Alkaline Phosphatase Treatment with Moderate Physical Activity Alleviates the Severity of Experimental Colitis in Obese Mice via Modulation of Gut Microbiota, Attenuation of Proinflammatory Cytokines, Oxidative Stress Biomarkers and DNA Oxidative Damage in Colonic Mucosa. Int J Mol Sci 2022; 23:ijms23062964. [PMID: 35328382 PMCID: PMC8955215 DOI: 10.3390/ijms23062964] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Revised: 03/03/2022] [Accepted: 03/04/2022] [Indexed: 12/16/2022] Open
Abstract
Inflammatory bowel diseases (IBD) are commonly considered as Crohn's disease and ulcerative colitis, but the possibility that the alterations in gut microbiota and oxidative stress may affect the course of experimental colitis in obese physically exercising mice treated with the intestinal alkaline phosphatase (IAP) has been little elucidated. Mice fed a high-fat-diet (HFD) or normal diet (ND) for 14 weeks were randomly assigned to exercise on spinning wheels (SW) for 7 weeks and treated with IAP followed by intrarectal administration of TNBS. The disease activity index (DAI), grip muscle strength test, oxidative stress biomarkers (MDA, SOD, GSH), DNA damage (8-OHdG), the plasma levels of cytokines IL-2, IL-6, IL-10, IL-12p70, IL-17a, TNF-α, MCP-1 and leptin were assessed, and the stool composition of the intestinal microbiota was determined by next generation sequencing (NGS). The TNBS-induced colitis was worsened in obese sedentary mice as manifested by severe colonic damage, an increase in DAI, oxidative stress biomarkers, DNA damage and decreased muscle strength. The longer running distance and weight loss was observed in mice given IAP or subjected to IAP + SW compared to sedentary ones. Less heterogeneous microbial composition was noticed in sedentary obese colitis mice and this effect disappeared in IAP + SW mice. Absence of Alistipes, lower proportion of Turicibacter, Proteobacteria and Faecalibacterium, an increase in Firmicutes and Clostridium, a decrease in oxidative stress biomarkers, 8-OHdG content and proinflammatory cytokines were observed in IAP + SW mice. IAP supplementation in combination with moderate physical activity attenuates the severity of murine colitis complicated by obesity through a mechanism involving the downregulation of the intestinal cytokine/chemokine network and oxidative stress, the modulation of the gut microbiota and an improvement of muscle strength.
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Aguilar-Lopez M, Dinsmoor AM, Ho TTB, Donovan SM. A systematic review of the factors influencing microbial colonization of the preterm infant gut. Gut Microbes 2022; 13:1-33. [PMID: 33818293 PMCID: PMC8023245 DOI: 10.1080/19490976.2021.1884514] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Prematurity coupled with the necessary clinical management of preterm (PT) infants introduces multiple factors that can interfere with microbial colonization. This study aimed to review the perinatal, physiological, pharmacological, dietary, and environmental factors associated with gut microbiota of PT infants. A total of 587 articles were retrieved from a search of multiple databases. Sixty studies were included in the review after removing duplicates and articles that did not meet the inclusion criteria. Review of this literature revealed that evidence converged on the effect of postnatal age, mode of delivery, use of antibiotics, and consumption of human milk in the composition of gut microbiota of PT infants. Less evidence was found for associations with race, sex, use of different fortifiers, macronutrients, and other medications. Future studies with rich metadata are needed to further explore the impact of the PT exposome on the development of the microbiota in this high-risk population.
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Affiliation(s)
- Miriam Aguilar-Lopez
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, USA
| | - Andrew M. Dinsmoor
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, USA
| | - Thao T. B. Ho
- Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, USA
| | - Sharon M. Donovan
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, USA,Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Urbana, USA,CONTACT Sharon M. Donovan Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, 339 Bevier Hall 905 S. Goodwin Avenue, Urbana, IL61801, USA
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10
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Abbasi A, Aghebati-Maleki L, Homayouni-Rad A. The promising biological role of postbiotics derived from probiotic Lactobacillus species in reproductive health. Crit Rev Food Sci Nutr 2021; 62:8829-8841. [PMID: 34152234 DOI: 10.1080/10408398.2021.1935701] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Recent investigations have meaningfully developed our knowledge of the features of the reproductive microbiome/metabolome profile and their relations with host responses to offer an optimal milieu for the development of the embryo during the peri-implantation period and throughout pregnancy. In this context, the establishment of homeostatic circumstances in the Female Reproductive Tract (FRT), in various physiological periods, is a significant challenge, which appears the application of postbiotics can facilitate the achievement of this goal. So, currently, scientific literature confirms that postbiotics due to their antimicrobial, antiviral, and immunomodulatory properties can be considered as a novel biotherapeutic approach. Future investigation in this field will shed more translational mechanistic understanding of the interaction of the postbiotics derived from vaginal Lactobacilli with females' health and reproduction.
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Affiliation(s)
- Amin Abbasi
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.,Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Aziz Homayouni-Rad
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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11
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Westaway JAF, Huerlimann R, Miller CM, Kandasamy Y, Norton R, Rudd D. Methods for exploring the faecal microbiome of premature infants: a review. Matern Health Neonatol Perinatol 2021; 7:11. [PMID: 33685524 PMCID: PMC7941982 DOI: 10.1186/s40748-021-00131-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 03/01/2021] [Indexed: 12/13/2022] Open
Abstract
The premature infant gut microbiome plays an important part in infant health and development, and recognition of the implications of microbial dysbiosis in premature infants has prompted significant research into these issues. The approaches to designing investigations into microbial populations are many and varied, each with its own benefits and limitations. The technique used can influence results, contributing to heterogeneity across studies. This review aimed to describe the most common techniques used in researching the preterm infant microbiome, detailing their various limitations. The objective was to provide those entering the field with a broad understanding of available methodologies, so that the likely effects of their use can be factored into literature interpretation and future study design. We found that although many techniques are used for characterising the premature infant microbiome, 16S rRNA short amplicon sequencing is the most common. 16S rRNA short amplicon sequencing has several benefits, including high accuracy, discoverability and high throughput capacity. However, this technique has limitations. Each stage of the protocol offers opportunities for the injection of bias. Bias can contribute to variability between studies using 16S rRNA high throughout sequencing. Thus, we recommend that the interpretation of previous results and future study design be given careful consideration.
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Affiliation(s)
- Jacob A F Westaway
- James Cook University, 1 McGregor Road, Smithfield, QLD, 4878, Australia.
| | - Roger Huerlimann
- James Cook University, 1 James Cook Dr, Douglas, QLD, 4811, Australia
| | - Catherine M Miller
- James Cook University, 1 McGregor Road, Smithfield, QLD, 4878, Australia
| | - Yoga Kandasamy
- Townsville University Hospital, 100 Angus Smith Dr, Douglas, QLD, 4814, Australia
| | - Robert Norton
- Pathology Queensland, 100 Angus Smith Dr, Douglas, QLD, 4814, Australia
| | - Donna Rudd
- James Cook University, 1 James Cook Dr, Douglas, QLD, 4811, Australia
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12
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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: 57] [Impact Index Per Article: 14.3] [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.
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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.)
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13
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Eukaryotic and Prokaryotic Microbiota Interactions. Microorganisms 2020; 8:microorganisms8122018. [PMID: 33348551 PMCID: PMC7767281 DOI: 10.3390/microorganisms8122018] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 11/30/2020] [Accepted: 12/05/2020] [Indexed: 12/12/2022] Open
Abstract
The nature of the relationship between the communities of microorganisms making up the microbiota in and on a host body has been increasingly explored in recent years. Microorganisms, including bacteria, archaea, viruses, parasites and fungi, have often long co-evolved with their hosts. In human, the structure and diversity of microbiota vary according to the host’s immunity, diet, environment, age, physiological and metabolic status, medical practices (e.g., antibiotic treatment), climate, season and host genetics. The recent advent of next generation sequencing (NGS) technologies enhanced observational capacities and allowed for a better understanding of the relationship between distinct microorganisms within microbiota. The interaction between the host and their microbiota has become a field of research into microorganisms with therapeutic and preventive interest for public health applications. This review aims at assessing the current knowledge on interactions between prokaryotic and eukaryotic communities. After a brief description of the metagenomic methods used in the studies were analysed, we summarise the findings of available publications describing the interaction between the bacterial communities and protozoa, helminths and fungi, either in vitro, in experimental models, or in humans. Overall, we observed the existence of a beneficial effect in situations where some microorganisms can improve the health status of the host, while the presence of other microorganisms has been associated with pathologies, resulting in an adverse effect on human health.
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14
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Abbasi A, Aghebati-Maleki A, Yousefi M, Aghebati-Maleki L. Probiotic intervention as a potential therapeutic for managing gestational disorders and improving pregnancy outcomes. J Reprod Immunol 2020; 143:103244. [PMID: 33186834 DOI: 10.1016/j.jri.2020.103244] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 10/25/2020] [Indexed: 02/06/2023]
Abstract
Recent molecular investigations have significantly developed our knowledge of the characteristics of the reproductive microbiome and their associations with host responses to provide an ideal milieu for the development of the embryo during the peri-implantation period and throughout pregnancy as well as to provide a successful in vitro fertilization and appropriate reproductive outcomes. In this context, the establishment of microbial homeostasis in the female reproductive tract, in various physiological periods, is a substantial challenge, which appears the application of probiotics can facilitate the achievement of this goal. So that, currently, probiotics due to its safe and natural features can be considered as a novel biotherapeutic approach. In this review, we comprehensively discuss the bacterial, fungal, and viral diversity detected in the reproductive tract, and their associations with the establishment of dysbiosis/eubiosis conditions as well as we present the significant outcomes on probiotic intervention as an efficient biotherapeutic strategy for management of gestational disorders and improve pregnancy outcomes.
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Affiliation(s)
- Amin Abbasi
- Department of Food Science and Technology, Faculty of Nutrition & Food Sciences, Tabriz, Iran; Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali Aghebati-Maleki
- Student's Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Yousefi
- Stem Cell Research Center, Tabriz University of Medical Science, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leili Aghebati-Maleki
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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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.
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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
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16
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In search for interplay between stool microRNAs, microbiota and short chain fatty acids in Crohn's disease - a preliminary study. BMC Gastroenterol 2020; 20:307. [PMID: 32958038 PMCID: PMC7507689 DOI: 10.1186/s12876-020-01444-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 09/09/2020] [Indexed: 12/19/2022] Open
Abstract
Background Inflammatory bowel diseases are classic polygenic disorders, with genetic loads that reflect immunopathological processes in response to the intestinal microbiota. Herein we performed the multiomics analysis by combining the large scale surveys of gut bacterial community, stool microRNA (miRNA) and short chain fatty acid (SCFA) signatures to correlate their association with the activity of Crohn’s disease (CD). Methods DNA, miRNA, and metabolites were extracted from stool samples of 15 CD patients, eight with active disease and seven in remission, and nine healthy individuals. Microbial, miRNA and SCFA profiles were assessed using datasets from 16S rRNA sequencing, Nanostring miRNA and GC-MS targeted analysis, respectively. Results Pairwise comparisons showed that 9 and 23 taxa differed between controls and CD patients with active and inactive disease, respectively. Six taxa were common to both comparisons, whereas four taxa differed in CD patients. α-Diversity was lower in both CD groups than in controls. The levels of 13 miRNAs differed (p-value < 0.05; FC > 1.5) in CD patients and controls before FDR correction and 4 after. Of six SCFAs, the levels of two differed significantly (p-value < 0.05, FC > 1.5) in CD patients and controls, and the levels of four differed in patients with active and inactive CD. PLS-DA revealed models with smallest error rate for controls in bacterial component and inactive disease in metabolites. Conclusion A complex interrelationship may exist between gut dysbiosis, miRNA profiling and SCFA level in response to intestinal inflammation.
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17
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Kulecka M, Fraczek B, Mikula M, Zeber-Lubecka N, Karczmarski J, Paziewska A, Ambrozkiewicz F, Jagusztyn-Krynicka K, Cieszczyk P, Ostrowski J. The composition and richness of the gut microbiota differentiate the top Polish endurance athletes from sedentary controls. Gut Microbes 2020; 11:1374-1384. [PMID: 32401138 PMCID: PMC7524299 DOI: 10.1080/19490976.2020.1758009] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Little data are available on the subject of gut microbiota composition in endurance athletes as well as connections between diet and specific bacteria abundance. However, most studies suggest that athletes' microbiota undergoes major alterations, which may contribute to increased physical performance. Therefore, we decided to investigate differences in gut microbiota between healthy controls and endurance athletes. MATERIALS AND METHODS Stools samples were collected from 14 marathon runners, 11 cross-country skiers and 46 sedentary healthy controls. The athletes' diet evaluation was performed with 24-h diet recall, using the Aliant programme. The 16S gene sequencing was performed using the Ion 16S Metagenomics Kit on Ion Torrent PGM sequencer. Taxonomic classification and diversity indices computation was performed with Mothur. RESULTS 20 and 5 taxa differentiated healthy controls from marathon runners and cross-country skiers, respectively. Both groups presented a lowered abundance of major gut microbiota genus, Bacteroidetes and higher abundance of Prevotella. The athletes' microbiome was also more diverse in cross-country skiers than the one of sedentary controls (Simpson index p-value at 0.025). Thirty-one strong correlations (Spearman's coefficient > 0.6) were uncovered between bacteria abundance and diet, including inverse correlation of Prevotella with sucrose intake, Phascolarctobacterium with polyunsaturated fatty acids as well as positive correlation of Christensenellaceae with folic acid intake and Agathobacter with fiber amount in diet. CONCLUSIONS The excessive training associates with both differences in composition and promotion of higher bacterial diversity. Taxons enriched in athletes are known to participate in fiber fermentation.
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Affiliation(s)
- Maria Kulecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland,Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Barbara Fraczek
- Department of Sports Medicine and Human Nutrition, Institute of Biomedical Sciences, Faculty of Physical Education and Sport, University of Physical Education in Krakow, Krakow, Poland
| | - Michal Mikula
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Natalia Zeber-Lubecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Jakub Karczmarski
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Agnieszka Paziewska
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland,Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Filip Ambrozkiewicz
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
| | - Katarzyna Jagusztyn-Krynicka
- Department of Bacterial Genetics, Institute of Microbiology, Faculty of Biology, University of Warsaw, Warsaw, Poland
| | - Paweł Cieszczyk
- Department of Molecular Biology, Faculty of Physical Education, Gdansk University of Physical Education and Sport, Gdansk, Poland
| | - Jerzy Ostrowski
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland,Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland,CONTACT Jerzy Ostrowski Maria Sklodowska-Curie National Research Institute of Oncology, Roentgena 5, Warsaw02-781, Poland
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18
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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: 143] [Impact Index Per Article: 28.6] [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.
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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.
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Chernevskaya E, Beloborodova N, Klimenko N, Pautova A, Shilkin D, Gusarov V, Tyakht A. Serum and fecal profiles of aromatic microbial metabolites reflect gut microbiota disruption in critically ill patients: a prospective observational pilot study. Crit Care 2020; 24:312. [PMID: 32513224 PMCID: PMC7278238 DOI: 10.1186/s13054-020-03031-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2020] [Accepted: 05/27/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND High serum levels of certain aromatic microbial metabolites (AMM) are associated with severity and mortality in critically ill patients. Omics-based studies suggest gut dysbiosis and reduced microbiome diversity in critical conditions. However, the landscape of gut microbial metabolites is still to be outlined, not to mention the interplay correlation between the metabolome and gut microbiome in critically ill patients. The aim of this study was to analyze the association between serum and fecal levels of AMM and compare them with the composition of gut microbiota in critically ill patients in the acute and chronic stages. METHODS In this prospective observational pilot study, we analyzed the temporal dynamics of the gut microbiome and the AMM spectrum across two distinct subgroups-acute critical ill (ACI) patients with nosocomial pneumonia and chronically critically ill (CCI) patients (9 subjects each group)-as well as performed comparison with 23 healthy volunteers. The AMM levels for each patient were measured using GC-MS in simultaneously taken serum and fecal samples (SFS). These parameters were compared with 16S rRNA fecal microbiome profiles. RESULTS The observed proportions of bacterial taxa suggest a significant gut dysbiosis in the ACI and the CCI patients. Stronger imbalance in microbiome composition and dynamics observed in the ACI patients compared to the CCI ones resonates with a higher severity in the former group. The total levels of AMM in serum samples were higher for the ACI patients than for the CCI patients (3.7 (1.4-6.3) and 1.1 (1.0-1.6) μM, respectively; p = 0.0003). The qualitative composition of the SFS was also altered. We discovered significant associations between gut microbial taxa levels and metabolite concentrations in blood serum as well as in feces in each of the ACI and the CCI patients. CONCLUSIONS Aromatic microbial metabolite profiles in the gut and the serum are interlinked and reflect a disruption of the gut microbial community in critically ill patients.
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Affiliation(s)
- Ekaterina Chernevskaya
- Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 25-2 Petrovka str., Moscow, Russia, 107031.
| | - Natalia Beloborodova
- Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 25-2 Petrovka str., Moscow, Russia, 107031
| | - Natalia Klimenko
- Atlas Biomed Group - Knomics LLC, 31 Malaya Nikitskaya str., Moscow, Russia, 121069
- Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology Russian Academy of Sciences, 34/5 Vavilova str., Moscow, Russia, 119334
| | - Alisa Pautova
- Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, 25-2 Petrovka str., Moscow, Russia, 107031
| | - Dmitrii Shilkin
- N. Pirogov National Medical Surgical Center, 70 Nizhnyaya Pervomayskaya str., Moscow, Russia, 105203
| | - Vitaliy Gusarov
- N. Pirogov National Medical Surgical Center, 70 Nizhnyaya Pervomayskaya str., Moscow, Russia, 105203
| | - Alexander Tyakht
- Atlas Biomed Group - Knomics LLC, 31 Malaya Nikitskaya str., Moscow, Russia, 121069
- Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology Russian Academy of Sciences, 34/5 Vavilova str., Moscow, Russia, 119334
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20
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Cukrowska B, Bierła JB, Zakrzewska M, Klukowski M, Maciorkowska E. The Relationship between the Infant Gut Microbiota and Allergy. The Role of Bifidobacterium breve and Prebiotic Oligosaccharides in the Activation of Anti-Allergic Mechanisms in Early Life. Nutrients 2020; 12:nu12040946. [PMID: 32235348 PMCID: PMC7230322 DOI: 10.3390/nu12040946] [Citation(s) in RCA: 105] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 03/23/2020] [Accepted: 03/26/2020] [Indexed: 12/15/2022] Open
Abstract
The increase in allergy prevalence observed in recent decades may be a consequence of early intestinal dysbiosis. The intestinal microbiota is formed in the first 1000 days of life, when it is particularly sensitive to various factors, such as the composition of the mother’s microbiota, type of delivery, infant’s diet, number of siblings, contact with animals, and antibiotic therapy. Breastfeeding and vaginal birth favorably affect the formation of an infant’s intestinal microbiota and protect against allergy development. The intestinal microbiota of these infants is characterized by an early dominance of Bifidobacterium, which may have a significant impact on the development of immune tolerance. Bifidobacterium breve is a species commonly isolated from the intestines of healthy breastfed infants and from human milk. This review outlines the most important environmental factors affecting microbiota formation and the importance of Bifidobacterium species (with a particular emphasis on Bifidobacterium breve) in microbiota modulation towards anti-allergic processes. In addition, we present the concept, which assumes that infant formulas containing specific probiotic Bifidobacterium breve strains and prebiotic oligosaccharides may be useful in allergy management in non-breastfed infants.
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Affiliation(s)
- Bożena Cukrowska
- Department of Pathology, The Children Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland;
- Correspondence: ; Tel.: +48-22-815-19-69
| | - Joanna B. Bierła
- Department of Pathology, The Children Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730 Warsaw, Poland;
| | - Magdalena Zakrzewska
- Department of Developmental Age Medicine and Paediatric Nursing, Faculty of Health Sciences, Medical University of Bialystok, Szpitalna St. 37, 15-295 Białystok, Poland; (M.Z.); (E.M.)
| | - Mark Klukowski
- Department of Pediatrics and Pulmonary Diseases, Faculty of Health Sciences, Medical University of Bialystok, Jerzego Waszyngtona St. 17, 15-274 Białystok, Poland;
| | - Elżbieta Maciorkowska
- Department of Developmental Age Medicine and Paediatric Nursing, Faculty of Health Sciences, Medical University of Bialystok, Szpitalna St. 37, 15-295 Białystok, Poland; (M.Z.); (E.M.)
- Department of Pediatrics and Pulmonary Diseases, Faculty of Health Sciences, Medical University of Bialystok, Jerzego Waszyngtona St. 17, 15-274 Białystok, Poland;
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21
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López-Moreno A, Aguilera M. Probiotics Dietary Supplementation for Modulating Endocrine and Fertility Microbiota Dysbiosis. Nutrients 2020; 12:E757. [PMID: 32182980 PMCID: PMC7146451 DOI: 10.3390/nu12030757] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 03/06/2020] [Accepted: 03/09/2020] [Indexed: 12/15/2022] Open
Abstract
Human microbiota seems to play a key role in endocrine and reproductive systems. Fortunately, microbiota reproductive dysbiosis start to be treated by probiotics using typical species from genus Lactobacillus. This work presents the compiled and analysed results from the most up-to-date information from clinical trials regarding microbiota, fertility, probiotics and oral route administration, reviewing open access scientific documents. These studies analyse the clinical impact of probiotics administered on several endocrine disorders' manifestations in women: mastitis; vaginal dysbiosis; pregnancy complication disorders; and polycystic ovary syndrome. In all cases, the clinical modulation achieved by probiotics was evaluated positively through the improvement of specific disease outcomes with the exception of the pregnancy disorders studies, where the sample sizes results were statistically insufficient. High amounts of studies were discarded because no data were provided on specific probiotic strains, doses, impact on the individual autochthon microbiota, or data regarding specific hormonal values modifications and endocrine regulation effects. However, most of the selected studies with probiotics contained no protocolised administration. Therefore, we consider that intervention studies with probiotics might allocate the focus, not only in obtaining a final outcome, but in how to personalise the administration according to the disorder to be palliated.
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Affiliation(s)
- Ana López-Moreno
- Department of Microbiology, Faculty of Pharmacy, University of Granada, Campus of Cartuja, 18071 Granada, Spain
- Institute of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, 18016 Armilla, Granada, Spain
| | - Margarita Aguilera
- Department of Microbiology, Faculty of Pharmacy, University of Granada, Campus of Cartuja, 18071 Granada, Spain
- Institute of Nutrition and Food Technology “José Mataix”, Center of Biomedical Research, University of Granada, 18016 Armilla, Granada, Spain
- IBS: Instituto de Investigación Biosanitaria ibs., 18012 Granada, Spain
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22
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Mueller NT, Hourigan SK, Hoffmann DE, Levy L, von Rosenvinge EC, Chou B, Dominguez-Bello MG. Bacterial Baptism: Scientific, Medical, and Regulatory Issues Raised by Vaginal Seeding of C-Section-Born Babies. THE JOURNAL OF LAW, MEDICINE & ETHICS : A JOURNAL OF THE AMERICAN SOCIETY OF LAW, MEDICINE & ETHICS 2019; 47:568-578. [PMID: 31957590 PMCID: PMC7908762 DOI: 10.1177/1073110519897732] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
Several lines of evidence suggest that children born via Cesarean section (C-section) are at greater risk for adverse health outcomes including allergies, asthma and obesity. Vaginal seeding is a medical procedure in which infants born by C-section are swabbed immediately after birth with vaginal secretions from the mother. This procedure has been proposed as a way to transfer the mother's vaginal microbiome to the child, thereby restoring the natural exposure that occurs during vaginal birth that is interrupted in the case of babies born via C-section. Preliminary evidence indicates partial restoration of microbes. However, there is insufficient evidence to determine the health benefits of the procedure. Several studies, including trial, are currently underway. At the same time, in the clinic setting, doctors are increasingly being asked to by expectant mothers to have their babies seeded. This article reports on the current research on this procedure and the issues it raises for regulators, researchers, physicians, and patients.
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Affiliation(s)
- Noel T Mueller
- Noel T. Mueller, Ph.D., M.P.H., is an Assistant Professor of Medicine, Johns Hopkins Bloomberg School of Public Health. Suchitra K. Hourigan, M.D., is a Pediatric Gastroenterology & Pediatrics, INOVA Health. Diane E. Hoffmann, J.D., Sc.M., is a Professor of Law, University of Maryland Carey School of Law. Lauren Levy, J.D., M.P.H., is Health Officer, Cecil County, MD Health Department. Erik C. von Rosenvinge, M.D., is an Associate Professor, Medicine, University of Maryland School of Medicine; Chief of Gastroenterology, VA Maryland Health Care System. Betty Chou, M.D., is an Assistant Professor of Gynecology and Obstetrics, Johns Hopkins University School of Medicine. Maria-Gloria Dominguez-Bello, Ph.D., is a Professor, Dept. of Biochemistry and Microbiology, Rutgers School of Environmental and Biological Sciences
| | - Suchitra K Hourigan
- Noel T. Mueller, Ph.D., M.P.H., is an Assistant Professor of Medicine, Johns Hopkins Bloomberg School of Public Health. Suchitra K. Hourigan, M.D., is a Pediatric Gastroenterology & Pediatrics, INOVA Health. Diane E. Hoffmann, J.D., Sc.M., is a Professor of Law, University of Maryland Carey School of Law. Lauren Levy, J.D., M.P.H., is Health Officer, Cecil County, MD Health Department. Erik C. von Rosenvinge, M.D., is an Associate Professor, Medicine, University of Maryland School of Medicine; Chief of Gastroenterology, VA Maryland Health Care System. Betty Chou, M.D., is an Assistant Professor of Gynecology and Obstetrics, Johns Hopkins University School of Medicine. Maria-Gloria Dominguez-Bello, Ph.D., is a Professor, Dept. of Biochemistry and Microbiology, Rutgers School of Environmental and Biological Sciences
| | - Diane E Hoffmann
- Noel T. Mueller, Ph.D., M.P.H., is an Assistant Professor of Medicine, Johns Hopkins Bloomberg School of Public Health. Suchitra K. Hourigan, M.D., is a Pediatric Gastroenterology & Pediatrics, INOVA Health. Diane E. Hoffmann, J.D., Sc.M., is a Professor of Law, University of Maryland Carey School of Law. Lauren Levy, J.D., M.P.H., is Health Officer, Cecil County, MD Health Department. Erik C. von Rosenvinge, M.D., is an Associate Professor, Medicine, University of Maryland School of Medicine; Chief of Gastroenterology, VA Maryland Health Care System. Betty Chou, M.D., is an Assistant Professor of Gynecology and Obstetrics, Johns Hopkins University School of Medicine. Maria-Gloria Dominguez-Bello, Ph.D., is a Professor, Dept. of Biochemistry and Microbiology, Rutgers School of Environmental and Biological Sciences
| | - Lauren Levy
- Noel T. Mueller, Ph.D., M.P.H., is an Assistant Professor of Medicine, Johns Hopkins Bloomberg School of Public Health. Suchitra K. Hourigan, M.D., is a Pediatric Gastroenterology & Pediatrics, INOVA Health. Diane E. Hoffmann, J.D., Sc.M., is a Professor of Law, University of Maryland Carey School of Law. Lauren Levy, J.D., M.P.H., is Health Officer, Cecil County, MD Health Department. Erik C. von Rosenvinge, M.D., is an Associate Professor, Medicine, University of Maryland School of Medicine; Chief of Gastroenterology, VA Maryland Health Care System. Betty Chou, M.D., is an Assistant Professor of Gynecology and Obstetrics, Johns Hopkins University School of Medicine. Maria-Gloria Dominguez-Bello, Ph.D., is a Professor, Dept. of Biochemistry and Microbiology, Rutgers School of Environmental and Biological Sciences
| | - Erik C von Rosenvinge
- Noel T. Mueller, Ph.D., M.P.H., is an Assistant Professor of Medicine, Johns Hopkins Bloomberg School of Public Health. Suchitra K. Hourigan, M.D., is a Pediatric Gastroenterology & Pediatrics, INOVA Health. Diane E. Hoffmann, J.D., Sc.M., is a Professor of Law, University of Maryland Carey School of Law. Lauren Levy, J.D., M.P.H., is Health Officer, Cecil County, MD Health Department. Erik C. von Rosenvinge, M.D., is an Associate Professor, Medicine, University of Maryland School of Medicine; Chief of Gastroenterology, VA Maryland Health Care System. Betty Chou, M.D., is an Assistant Professor of Gynecology and Obstetrics, Johns Hopkins University School of Medicine. Maria-Gloria Dominguez-Bello, Ph.D., is a Professor, Dept. of Biochemistry and Microbiology, Rutgers School of Environmental and Biological Sciences
| | - Betty Chou
- Noel T. Mueller, Ph.D., M.P.H., is an Assistant Professor of Medicine, Johns Hopkins Bloomberg School of Public Health. Suchitra K. Hourigan, M.D., is a Pediatric Gastroenterology & Pediatrics, INOVA Health. Diane E. Hoffmann, J.D., Sc.M., is a Professor of Law, University of Maryland Carey School of Law. Lauren Levy, J.D., M.P.H., is Health Officer, Cecil County, MD Health Department. Erik C. von Rosenvinge, M.D., is an Associate Professor, Medicine, University of Maryland School of Medicine; Chief of Gastroenterology, VA Maryland Health Care System. Betty Chou, M.D., is an Assistant Professor of Gynecology and Obstetrics, Johns Hopkins University School of Medicine. Maria-Gloria Dominguez-Bello, Ph.D., is a Professor, Dept. of Biochemistry and Microbiology, Rutgers School of Environmental and Biological Sciences
| | - Maria-Gloria Dominguez-Bello
- Noel T. Mueller, Ph.D., M.P.H., is an Assistant Professor of Medicine, Johns Hopkins Bloomberg School of Public Health. Suchitra K. Hourigan, M.D., is a Pediatric Gastroenterology & Pediatrics, INOVA Health. Diane E. Hoffmann, J.D., Sc.M., is a Professor of Law, University of Maryland Carey School of Law. Lauren Levy, J.D., M.P.H., is Health Officer, Cecil County, MD Health Department. Erik C. von Rosenvinge, M.D., is an Associate Professor, Medicine, University of Maryland School of Medicine; Chief of Gastroenterology, VA Maryland Health Care System. Betty Chou, M.D., is an Assistant Professor of Gynecology and Obstetrics, Johns Hopkins University School of Medicine. Maria-Gloria Dominguez-Bello, Ph.D., is a Professor, Dept. of Biochemistry and Microbiology, Rutgers School of Environmental and Biological Sciences
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23
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Microbial and Nutritional Programming-The Importance of the Microbiome and Early Exposure to Potential Food Allergens in the Development of Allergies. Nutrients 2018; 10:nu10101541. [PMID: 30340391 PMCID: PMC6212882 DOI: 10.3390/nu10101541] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Revised: 10/15/2018] [Accepted: 10/16/2018] [Indexed: 02/06/2023] Open
Abstract
The “microbiota hypothesis” ties the increase in allergy rates observed in highly developed countries over the last decades to disturbances in the gut microbiota. Gut microbiota formation depends on a number of factors and occurs over approximately 1000 days of life, including the prenatal period. During this period the microbiota helps establish the functional immune phenotype, including immune tolerance. The development of immune tolerance depends also on early exposure to potential food allergens, a process referred to as nutritional programming. This article elaborates on the concepts of microbial and nutritional programming and their role in the primary prevention of allergy.
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Probiotics for Preterm Infants: A Strain-Specific Systematic Review and Network Meta-analysis. J Pediatr Gastroenterol Nutr 2018; 67:103-122. [PMID: 29384838 DOI: 10.1097/mpg.0000000000001897] [Citation(s) in RCA: 120] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
OBJECTIVES Several randomized controlled trials (RCTs) on the use of probiotics to reduce morbidity and mortality in preterm infants have provided inconsistent results. Although meta-analyses that group all of the used strains together are suggesting efficacy, it is not possible to determine the most effective strain that is more relevant to the clinician. We therefore used a network meta-analysis (NMA) approach to identify strains with greatest efficacy. METHODS A PubMed search identified placebo-controlled or head-to-head RCTs investigating probiotics in preterm infants. From trials that recorded mortality, necrotizing enterocolitis, late-onset sepsis, or time until full enteral feeding as outcomes, data were extracted and Bayesian hierarchical random-effects models were run to construct a NMA. RESULTS Fifty-one RCTs involving 11,231 preterm infants were included. Most strains or combinations of strains were only studied in one or a few RCTs. Only 3 of 25 studied probiotic treatment combinations showed significant reduction in mortality rates. Seven treatments reduced necrotizing enterocolitis incidence, 2 reduced late-onset sepsis, and 3 reduced time until full enteral feeding. There was no clear overlap of strains, which were effective on multiple outcome domains. CONCLUSIONS This NMA showed efficacy in reducing mortality and morbidity only in a minority of the studied strains or combinations. This may be due to an inadequate number, or size, of RCTs, or due to a true lack of effect for certain species. Further large and adequately powered RCTs using strains with the greatest apparent efficacy will be needed to more precisely define optimal treatment strategies.
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25
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Curtis JT, Assefa S, Francis A, Köhler GA. Fecal microbiota in the female prairie vole (Microtus ochrogaster). PLoS One 2018; 13:e0190648. [PMID: 29579049 PMCID: PMC5868765 DOI: 10.1371/journal.pone.0190648] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Accepted: 12/18/2017] [Indexed: 12/15/2022] Open
Abstract
We examined the fecal microbiota of female prairie voles. This species is socially and, likely, sexually monogamous, and thus serves as a valuable model in which to examine the interaction between the microbiota-gut-brain axis and social behavior. At present, little is known about the gastrointestinal microbiota of prairie voles; therefore, we performed a first characterization of the fecal microbiota using 16S rRNA gene amplicon sequencing. Semiconductor sequencing technology on an Ion Torrent PGM platform was used to assess the composition of fecal microbiotas from twelve female prairie voles. Following quality filtering, 1,017,756 sequencing reads were classified from phylum to genus level. At the phylum level, Firmicutes, Bacteroidetes, and Saccharibacteria were the predominant taxa, while the Bacteriodales, Erysipelotrichaceae, Ruminococcaceae, and Lachnospiraceae contributed the most dominant microbial groups and genera. Microbial community membership was most similar between vole sibling pairs, but consideration of taxon abundances weakened these associations. The interdependence of host factors such as genetics and behavior with the gastrointestinal microbiota is likely to be particularly pronounced in prairie voles. Our pilot characterization of the prairie vole intestinal microbiota revealed a microbial community composition remarkably consistent with the monogastric alimentary system of these rodents and their diet rich in complex plant carbohydrates. The highly social nature of these animals poses specific challenges to microbiome analyses that nonetheless are valuable for advancing research on the microbiota-gut-brain-behavior axis. Our study provides an important basis for future microbiome research in this emerging model organism for studying social behavior.
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Affiliation(s)
- J. Thomas Curtis
- Department of Pharmacology and Physiology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma, United States of America
| | - Senait Assefa
- Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma, United States of America
| | - Amie Francis
- Department of Pharmacology and Physiology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma, United States of America
| | - Gerwald A. Köhler
- Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, Tulsa, Oklahoma, United States of America
- * E-mail:
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Navarro F, Liu Y, Rhoads JM. Can probiotics benefit children with autism spectrum disorders? World J Gastroenterol 2016; 22:10093-10102. [PMID: 28028357 PMCID: PMC5155168 DOI: 10.3748/wjg.v22.i46.10093] [Citation(s) in RCA: 98] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2016] [Revised: 10/05/2016] [Accepted: 11/13/2016] [Indexed: 02/06/2023] Open
Abstract
Children with autism are commonly affected by gastrointestinal problems such as abdominal pain, constipation and diarrhea. In recent years, there has been a growing interest in the use of probiotics in this population, as it hypothetically may help to improve bowel habits and the behavioral and social functioning of these individuals. The gut microbiome plays an important role in the pathophysiology of organic as well as functional gastrointestinal disorders. Microbial modification with the use of antibiotics, probiotics, and fecal transplantation have been effective in the treatment of conditions such as recurrent Clostridium difficile infection, pouchitis, and irritable bowel syndrome. The present review presents a number of reported clinical, immunological and microbiome-related changes seen in children with autism compared to normally developed children. It also discusses gut inflammation, permeability concerns, and absorption abnormalities that may contribute to these problems. Most importantly, it discusses evidence, from human and animal studies, of a potential role of probiotics in the treatment of gastrointestinal symptoms in children with autism.
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Kulecka M, Paziewska A, Zeber-Lubecka N, Ambrozkiewicz F, Kopczynski M, Kuklinska U, Pysniak K, Gajewska M, Mikula M, Ostrowski J. Prolonged transfer of feces from the lean mice modulates gut microbiota in obese mice. Nutr Metab (Lond) 2016; 13:57. [PMID: 27559357 PMCID: PMC4995824 DOI: 10.1186/s12986-016-0116-8] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 08/16/2016] [Indexed: 12/31/2022] Open
Abstract
Background Transplanting a fecal sample from lean, healthy donors to obese recipients has been shown to improve metabolic syndrome symptoms. We therefore examined the gut microbiota in mice after administering a long-term, high-fat diet (HFD) supplemented with feces from lean mice through the fecal-oral route. Methods C57BL6/W mice were allowed to adapt to a non-specific pathogen free (SFP) environment for 2 weeks before being divided into three groups of 16 animals. Animals were fed for 28 weeks with a normal diet (ND), HFD or HFD supplemented with feces from ND-fed mice (HFDS). The composition of colonizing bacteria was evaluated in droppings collected under SPF conditions at the beginning of the study and at 12 and 28 weeks using an 16S Metagenomics Kit on Ion PGM sequencer. Results HFD and HFDS-fed mice attained (p < 0.05) greater body weights by weeks 6 and 5, respectively. HFDS-fed mice gained more weight than HFD-fed mice by week 25. Both species diversity and richness indices increased with time in HFDS mice only. Conclusions Prolonged HFD-fed mice supplementation with feces from lean mice altered bacteria species diversity and richness, accelerated the onset of obesity, and caused increased weight gain in the later weeks of the HFD regimen. Electronic supplementary material The online version of this article (doi:10.1186/s12986-016-0116-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Maria Kulecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Warsaw, Poland
| | - Agnieszka Paziewska
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Warsaw, Poland
| | - Natalia Zeber-Lubecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Warsaw, Poland
| | - Filip Ambrozkiewicz
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Warsaw, Poland
| | - Michal Kopczynski
- Department of Genetics, Maria Sklodowska-Curie Memorial, Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland
| | - Urszula Kuklinska
- Department of Genetics, Maria Sklodowska-Curie Memorial, Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland
| | - Kazimiera Pysniak
- Department of Genetics, Maria Sklodowska-Curie Memorial, Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland
| | - Marta Gajewska
- Department of Genetics, Maria Sklodowska-Curie Memorial, Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland
| | - Michal Mikula
- Department of Genetics, Maria Sklodowska-Curie Memorial, Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland
| | - Jerzy Ostrowski
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Warsaw, Poland ; Department of Genetics, Maria Sklodowska-Curie Memorial, Cancer Center and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland
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Zeber-Lubecka N, Kulecka M, Ambrozkiewicz F, Paziewska A, Goryca K, Karczmarski J, Rubel T, Wojtowicz W, Mlynarz P, Marczak L, Tomecki R, Mikula M, Ostrowski J. Limited prolonged effects of rifaximin treatment on irritable bowel syndrome-related differences in the fecal microbiome and metabolome. Gut Microbes 2016; 7:397-413. [PMID: 27662586 PMCID: PMC5046165 DOI: 10.1080/19490976.2016.1215805] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic functional disorder and its development may be linked, directly and indirectly, to intestinal dysbiosis. Here we investigated the interactions between IBS symptoms and the gut microbiome, including the relation to rifaximin (1200 mg daily; 11.2 g per a treatment). We recruited 72 patients, including 31 with IBS-D (diarrhea), 11 with IBS-C (constipation), and 30 with IBS-M (mixed constipation and diarrhea) and 30 healthy controls (HCs). Of them, 68%, 64%, and 53% patients with IBS-D, IBS-C, and IBS-M, respectively, achieved 10-12 week-term improvement after the rifaximin treatment. Stool samples were collected before and after the treatment, and fecal microbiotic profiles were analyzed by deep sequencing of 16S rRNA, while stool metabolic profiles were studied by hydrogen 1-nuclear magnetic resonance ((1)H-NMR) and gas chromatography-mass spectrometry (GC-MS). Of 26 identified phyla, only Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria were consistently found in all samples. Bacteroidetes was predominant in fecal samples from HCs and IBS-D and IBS-M subjects, whereas Firmicutes was predominant in samples from IBS-C subjects. Species richness, but not community diversity, differentiated all IBS patients from HCs. Metabolic fingerprinting, using NMR spectra, distinguished HCs from all IBS patients. Thirteen metabolites identified by GC-MS differed HCs and IBS patients. However, neither metagenomics nor metabolomics analyses identified significant differences between patients with and without improvement after treatment.
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Affiliation(s)
- Natalia Zeber-Lubecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Warsaw, Poland
| | - Maria Kulecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Warsaw, Poland
| | - Filip Ambrozkiewicz
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Warsaw, Poland
| | - Agnieszka Paziewska
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Warsaw, Poland
| | - Krzysztof Goryca
- Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Jakub Karczmarski
- Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Tymon Rubel
- Institute of Radioelectronics, Warsaw University of Technology, Warsaw, Poland
| | - Wojciech Wojtowicz
- Department of Bioorganic Chemistry Wroclaw University of Technology, Wroclaw, Poland
| | - Piotr Mlynarz
- Department of Bioorganic Chemistry Wroclaw University of Technology, Wroclaw, Poland
| | - Lukasz Marczak
- Institute of Bioorganic Chemistry Polish Academy of Sciences, Poznań, Poland
| | - Roman Tomecki
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Warsaw, Poland
| | - Michal Mikula
- Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
| | - Jerzy Ostrowski
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Center for Postgraduate Education, Warsaw, Poland,Department of Genetics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland
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