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Valdez-Martinez A, Santoyo-Alejandre MI, Arenas R, Fuentes-Venado CE, Ramírez-Lozada T, Bastida-González F, Calzada-Mendoza CC, Martínez-Herrera E, Pinto-Almazán R. Neonatal Mucormycosis: A Rare but Highly Lethal Fungal Infection in Term and Preterm Newborns-A 20-Year Systematic Review. Trop Med Infect Dis 2025; 10:86. [PMID: 40278759 PMCID: PMC12030780 DOI: 10.3390/tropicalmed10040086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2025] [Revised: 03/08/2025] [Accepted: 03/13/2025] [Indexed: 04/26/2025] Open
Abstract
BACKGROUND/OBJECTIVES Mucormycosis is a rare but life-threatening fungal infection, particularly in neonates, due to their undeveloped immune system. This systematic review aims to analyze the risk factors, clinical presentations, treatments, and outcomes of neonatal mucormycosis reported between 2004 and 2024. METHODS A systematic literature search was conducted in PubMed, Scopus, and Web of Science following PRISMA guidelines. Only studies reporting cases of mucormycosis in neonates (≤28 days old) were included. Data on risk factors, clinical features, diagnostic methods, antifungal therapies, surgical interventions, and outcomes were extracted and analyzed. RESULTS A total of 44 studies met the inclusion criteria, comprising 61 neonatal cases. The most common clinical presentations were gastrointestinal (n = 39), cutaneous (n = 19), rhino-orbito-cerebral (n = 2), and disseminated mucormycosis (n = 1). Diagnosis was primarily based on histopathology (93.4%) and fungal culture (26.2%). The main antifungal treatment was liposomal amphotericin B (63.9%), often combined with surgical debridement (60.6%). Mortality rates remained high (47.5%), particularly in cases of prematurely extreme neonates with angioinvasive disease or delayed diagnosis. CONCLUSIONS Neonatal mucormycosis remains a severe condition with high morbidity and mortality. Early diagnosis through a combination of clinical suspicion and laboratory confirmation, along with prompt antifungal therapy and surgical management, apparently is crucial for improving outcomes. Further studies are needed to optimize treatment strategies and improve neonatal survival.
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Affiliation(s)
- Alfredo Valdez-Martinez
- Sección de Micología, Hospital General “Dr. Manuel Gea González”, Tlalpan, Mexico City 14080, Mexico; (A.V.-M.); (R.A.)
- Hospital General del Zona 33, Instituto Mexicano del Seguro Social, Nayarit 63735, Mexico;
| | | | - Roberto Arenas
- Sección de Micología, Hospital General “Dr. Manuel Gea González”, Tlalpan, Mexico City 14080, Mexico; (A.V.-M.); (R.A.)
| | - Claudia Erika Fuentes-Venado
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Mexico City 11340, Mexico; (C.E.F.-V.); (C.C.C.-M.)
- Servicio de Medicina Física y Rehabilitación, Hospital General de Zona No 197, Texcoco 56160, Mexico
| | - Tito Ramírez-Lozada
- Servicio de Ginecología y Obstetricia, Hospital Regional de Alta Especialidad de Ixtapaluca, Instituto Mexicano de Seguro Social para el Bienestar (IMSS-BIENESTAR), Carretera Federal México-Puebla Km 34.5, Ixtapaluca 56530, Mexico;
| | - Fernando Bastida-González
- Laboratorio de Biología Molecular, Laboratorio Estatal de Salud Pública del Estado de México, Toluca de Lerdo 50130, Mexico;
| | - Claudia Camelia Calzada-Mendoza
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Mexico City 11340, Mexico; (C.E.F.-V.); (C.C.C.-M.)
| | - Erick Martínez-Herrera
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Mexico City 11340, Mexico; (C.E.F.-V.); (C.C.C.-M.)
- Fundación Vithas, Grupo Hospitalario Vithas, 28043 Madrid, Spain
- Efficiency, Quality, and Costs in Health Services Research Group (EFISALUD), Galicia Sur Health Research Institute (IISGS), Servizo Galego de Saúde-Universidade de Vigo (UVIGO), 36213 Vigo, Spain
| | - Rodolfo Pinto-Almazán
- Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Mexico City 11340, Mexico; (C.E.F.-V.); (C.C.C.-M.)
- Fundación Vithas, Grupo Hospitalario Vithas, 28043 Madrid, Spain
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Kim YH, Lee TY, Kim HY, Jeong SJ, Han JH, Shin JE, Lee JH, Kang CM. Natal factors influencing newborn's oral microbiome diversity. Sci Rep 2024; 14:28161. [PMID: 39548168 PMCID: PMC11568190 DOI: 10.1038/s41598-024-78609-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 11/02/2024] [Indexed: 11/17/2024] Open
Abstract
The early microbiota of neonates is crucial for developing the postnatal immune system and establishing normal physiological, metabolic, and neurological functions. This study aimed to investigate the factors influencing the diversity of the neonatal oral microbiome, including mother-to-newborn microbial transmission. The study includes a prospective cohort comprising 73 mothers and 87 neonates and a retrospective cohort comprising 991 mothers and 1,121 neonates. Samples from the maternal cervix and neonatal gastric, bronchial, and oral cavities were analyzed using culture-based methods. Neonatal oral swab samples were also analyzed using 16S rRNA gene sequencing to characterize microbial diversity and composition. Similar genera were detected in the neonatal gastric, bronchial, and oral samples, and the neonatal gastric culture was the most similar to the maternal cervical culture. In addition to mother-to-newborn microbial transmission, various natal factors including birth type, birth weight, delivery mode, maternal chorioamnionitis, maternal diabetes and the presence of microbes in other sites influenced neonatal oral microbiome diversity. Among these factors, the birth type was the most significant, and preterm neonates exhibited decreased oral microbiome diversity, with fewer beneficial bacteria and more pathogens. These findings could serve as a baseline for research on the establishment of the oral microbiota in preterm neonates and its health implications.
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Affiliation(s)
- Yoon-Hee Kim
- Department of Pediatric Dentistry, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seoul, 03722, Republic of Korea
| | - Tae Yang Lee
- Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, Republic of Korea
- Oral Science Research Center, Yonsei University College of Dentistry, Seoul, Republic of Korea
| | | | - Su Jin Jeong
- Statistics Support Part, Medical Science Research Institute, Kyung Hee University Medical Center, Seoul, Republic of Korea
| | - Jung Ho Han
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jeong Eun Shin
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jae-Ho Lee
- Department of Pediatric Dentistry, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seoul, 03722, Republic of Korea
- Oral Science Research Center, Yonsei University College of Dentistry, Seoul, Republic of Korea
| | - Chung-Min Kang
- Department of Pediatric Dentistry, Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seoul, 03722, Republic of Korea.
- Oral Science Research Center, Yonsei University College of Dentistry, Seoul, Republic of Korea.
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Sartor C, Mikrat Y, Grandvuillemin I, Caputo A, Ligi I, Chanteloup A, Penant G, Jardot P, Romain F, Levasseur A, Boubred F, La Scola B, Cassir N. Investigating transmission patterns among preterm neonates during an outbreak of necrotizing enterocolitis related to Clostridium butyricum using whole-genome sequencing. J Hosp Infect 2024; 152:21-27. [PMID: 39094736 DOI: 10.1016/j.jhin.2024.07.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 07/01/2024] [Accepted: 07/15/2024] [Indexed: 08/04/2024]
Abstract
BACKGROUND Necrotizing enterocolitis is the most severe life-threatening acquired gastrointestinal disorder among preterm neonates. We describe here an outbreak of Clostridium butyricum-related necrotizing enterocolitis in preterm neonates that occurred in three different neonatal centres, in southeast France. METHODS We defined a confirmed case of C. butyricum-related necrotizing enterocolitis in preterm neonates by the presence of clinical signs according to modified Bell criteria and C. butyricum identified from stool samples using real-time polymerase chain reaction or culture. A phylogenetic analysis of the isolated strains by whole-genome sequencing was also performed. RESULTS Between 5th and 27th January 2022, we identified 10 confirmed cases of C. butyricum-related necrotizing enterocolitis, including five from Neonatal Centre 1, four from Neonatal Centre 2, and one from Neonatal Centre 3. The attack rate of necrotizing enterocolitis in Neonatal Centre 1 was 7.1% (5/70). The positivity rate of C. butyricum detected from stool samples was higher during the outbreak period (37/276; 13.4%) than outside this period (7/369; 1.9%), while systematic screening was maintained (P<0.001). Phylogenetic analysis showed a clonality between strains inside four clusters. Two clusters included neonates hospitalized in different neonatal centres, suggesting the transmission of C. butyricum strains during the transfer of neonates between neonatal centres. CONCLUSIONS This outbreak of C. butyricum-related necrotizing enterocolitis confirms a cross-transmission between preterm neonates, including twin or triplet siblings, and involving necrotizing enterocolitis cases together with asymptomatic carriers. After three months of follow-up, no further cases were identified following the implementation of contact precautions with sporicidal agents.
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Affiliation(s)
- C Sartor
- Service de Prévention du Risque Infectieux (LESPRI), CLIN AP-HM Hôpitaux Universitaires de Marseille, Marseille, France
| | - Y Mikrat
- Microbes, Evolution, Phylogeny and Infections (MEPHI), AP-HM, Aix-Marseille Université, Marseille, France; IHU Méditerranée Infection, Marseille, France
| | - I Grandvuillemin
- Department of Neonatology, University Hospital La Conception, AP-HM, Hôpitaux Universitaires de Marseille, Marseille, France
| | - A Caputo
- Microbes, Evolution, Phylogeny and Infections (MEPHI), AP-HM, Aix-Marseille Université, Marseille, France; IHU Méditerranée Infection, Marseille, France
| | - I Ligi
- Department of Neonatology, University Hospital La Conception, AP-HM, Hôpitaux Universitaires de Marseille, Marseille, France
| | - A Chanteloup
- Microbes, Evolution, Phylogeny and Infections (MEPHI), AP-HM, Aix-Marseille Université, Marseille, France; IHU Méditerranée Infection, Marseille, France
| | - G Penant
- Microbes, Evolution, Phylogeny and Infections (MEPHI), AP-HM, Aix-Marseille Université, Marseille, France; IHU Méditerranée Infection, Marseille, France
| | - P Jardot
- Microbes, Evolution, Phylogeny and Infections (MEPHI), AP-HM, Aix-Marseille Université, Marseille, France; IHU Méditerranée Infection, Marseille, France
| | - F Romain
- Department of Public Health and Medical Information, Marseille, France
| | - A Levasseur
- Microbes, Evolution, Phylogeny and Infections (MEPHI), AP-HM, Aix-Marseille Université, Marseille, France; IHU Méditerranée Infection, Marseille, France
| | - F Boubred
- Neonatal Unit, C2 VN, University Hospital La Conception, APHM, AMU, Marseille, France
| | - B La Scola
- Microbes, Evolution, Phylogeny and Infections (MEPHI), AP-HM, Aix-Marseille Université, Marseille, France; IHU Méditerranée Infection, Marseille, France.
| | - N Cassir
- Microbes, Evolution, Phylogeny and Infections (MEPHI), AP-HM, Aix-Marseille Université, Marseille, France; IHU Méditerranée Infection, Marseille, France
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Di Chiara M, Lazzaro A, Scribano D, Trancassini M, Pietropaolo V, Sonnessa M, De Luca C, Prota R, Onestà E, Laccetta G, Terrin G. Reduced Gut Bacterial Diversity in Early Life Predicts Feeding Intolerance in Preterm Neonates. Trop Med Infect Dis 2024; 9:174. [PMID: 39195612 PMCID: PMC11359060 DOI: 10.3390/tropicalmed9080174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 07/10/2024] [Accepted: 07/12/2024] [Indexed: 08/29/2024] Open
Abstract
Microbiota plays a crucial role in intestinal maturation in preterm newborns. The clinical manifestation of the immaturity of the gastro-intestinal tract is called feeding intolerance (FI). This condition may resolve spontaneously or dramatically evolve into necrotizing enterocolitis. One of the most challenging tasks for the neonatologist is to identify those neonates that will develop the disease early in order to adequately provide nutrition to these patients, from the very first hours of life. A close interplay between the maturity of the gastro-intestinal tract and gut microbiota has been described; however, in preterm neonates, this relationship is still undefined. We analyzed the bacterial composition of stool samples, collected early in life, from 30 preterm newborns classified as intolerant or tolerant according to the degree of readiness of the gastro-intestinal tract to receive enteral nutrition. The Pielou evenness index was significantly increased in intolerant compared with tolerant newborns. Data corrected for confounding variables confirmed that the occurrence of gut maturation was independently influenced by Pielou evenness at birth. A lower bacterial diversity very early in life is associated with improved feeding tolerance in preterm newborns. The abundance analysis showed that neonates not ready to receive enteral nutrition for feeding intolerance show, after birth, an increased abundance of Proteobacteria, Lachnospiracae, Enterobacter and Acinetobacter. We can argue that those are the taxa that prevent the establishment of pioneer bacteria. A lower alpha-diversity, in the first days of life, may facilitate the seeding of beneficial pioneer bacteria that, in turn, drive healthy microbial colonization during neonatal life.
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Affiliation(s)
- Maria Di Chiara
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy (G.L.)
| | - Alessandro Lazzaro
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy; (A.L.); (D.S.); (M.T.)
| | - Daniela Scribano
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy; (A.L.); (D.S.); (M.T.)
| | - Maria Trancassini
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy; (A.L.); (D.S.); (M.T.)
| | - Valeria Pietropaolo
- Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy; (A.L.); (D.S.); (M.T.)
| | | | - Chiara De Luca
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy (G.L.)
| | - Rita Prota
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy (G.L.)
| | - Elisa Onestà
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy (G.L.)
| | - Gianluigi Laccetta
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy (G.L.)
| | - Gianluca Terrin
- Department of Maternal Infantile and Urological Sciences, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy (G.L.)
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Xiong X, Lu W, Xing F, Cai Y, Yang J, Yuan Y, Feng J, Chen X. Clinical characteristics of postoperative necrotizing enterocolitis in patients with congenital jejunoileal atresia and its risk factors. WORLD JOURNAL OF PEDIATRIC SURGERY 2024; 7:e000622. [PMID: 38511171 PMCID: PMC10952882 DOI: 10.1136/wjps-2023-000622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Accepted: 02/27/2024] [Indexed: 03/22/2024] Open
Abstract
Objective To review postoperative necrotizing enterocolitis (NEC) in patients with jejunoileal atresia (JIA) and to explore the potential risk factors related to the concurrence of NEC. Methods Patients diagnosed with JIA who received surgical treatment from January 2016 to June 2021 were enrolled. Demographics, viral infection of the fetus, transfusion within 48 hours before NEC, sepsis before JIA repair, pathological and anatomical classification of JIA, combined malformation, occurrence time of NEC after the operation, treatment, and prognosis of patients were analyzed. Patients were divided into NEC group and non-NEC group, and all patients were followed up for 3-6 months to observe for complications. Results A total of 180 patients with JIA were included, of whom 12 were diagnosed with NEC after surgery and 1 patient with NEC died during follow-up. The average age, birth weight, gestational age, proportion of premature infants, proportion of preoperative infections, and pathological classification of JIA did not significantly differ between the two groups. The probability of patients with proximal jejunal atresia (PJA) in the NEC group (58.3%) was higher than that in the non-NEC group (22.6%) (p=0.011), and patients with PJA had longer parenteral nutrition time than patients without PJA (26.64±9.21 days vs 15.11±6.58 days, p<0.001). Conclusion PJA was more likely to be associated with concurrent NEC after surgery, which is a highly NEC-related risk factor inherent in JIA.
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Affiliation(s)
- Xiaofeng Xiong
- Department of Pediatric Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China
- Department of Neonate Surgery, Wuhan Children's Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Wei Lu
- Department of Neonate Surgery, Wuhan Children's Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Fuzhong Xing
- Department of Neonate Surgery, Wuhan Children's Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yuan Cai
- Department of Neonate Surgery, Wuhan Children's Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jixin Yang
- Department of Pediatric Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yuhang Yuan
- Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | - Jiexiong Feng
- Department of Pediatric Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xuyong Chen
- Department of Pediatric Surgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, China
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Hu X, Liang H, Li F, Zhang R, Zhu Y, Zhu X, Xu Y. Necrotizing enterocolitis: current understanding of the prevention and management. Pediatr Surg Int 2024; 40:32. [PMID: 38196049 PMCID: PMC10776729 DOI: 10.1007/s00383-023-05619-3] [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] [Accepted: 12/15/2023] [Indexed: 01/11/2024]
Abstract
Necrotizing enterocolitis (NEC) is one of the diseases in neonates, with a high morbidity and mortality rate, especially in preterm infants. This review aimed to briefly introduce the latest epidemiology, susceptibility factors, and clinical diagnosis and presentation of NEC. We also organized new prevention strategies by risk factors according to different pathogeneses and then discussed new treatment methods based on Bell's staging and complications, and the classification of mild to high severity based on clinical and imaging manifestations. Such a generalization will help clinicians and researchers to gain a deeper understanding of the disease and to conduct more targeted classification, grading prevention, and exploration. We focused on prevention and treatment of the early and suspected stages of NEC, including the discovery of novel biomarkers and drugs to control disease progression. At the same time, we discussed its clinical application, future development, and shortcomings.
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Affiliation(s)
- Xiaohan Hu
- Institute of Pediatric, Children's Hospital of Soochow University, 92 Zhong Nan Street, Suzhou City, Jiangsu Province, China
- Department of Neonatology, Children's Hospital of Soochow University, 92 Zhong Nan Street, Suzhou City, Jiangsu Province, China
| | - Hansi Liang
- Jiangsu Key Laboratory of Gastrointestinal Tumor Immunology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Fang Li
- Department of Human Anatomy and Histology and Embryology, Soochow University, Suzhou, Jiangsu Province, China
| | - Rui Zhang
- Institute of Pediatric, Children's Hospital of Soochow University, 92 Zhong Nan Street, Suzhou City, Jiangsu Province, China
| | - Yanbo Zhu
- Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Xueping Zhu
- Institute of Pediatric, Children's Hospital of Soochow University, 92 Zhong Nan Street, Suzhou City, Jiangsu Province, China.
- Department of Neonatology, Children's Hospital of Soochow University, 92 Zhong Nan Street, Suzhou City, Jiangsu Province, China.
| | - Yunyun Xu
- Institute of Pediatric, Children's Hospital of Soochow University, 92 Zhong Nan Street, Suzhou City, Jiangsu Province, China.
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Hong L, Huang Y, Han J, Li S, Zhang L, Jiang S, Zhou Q, Cao X, Yu W, Yang Y, Hong S, Zhou Y, Yan W, Cao Y. Dynamics and Crosstalk between Gut Microbiota, Metabolome, and Fecal Calprotectin in Very Preterm Infants: Insights into Feeding Intolerance. Nutrients 2023; 15:4849. [PMID: 38004243 PMCID: PMC10674500 DOI: 10.3390/nu15224849] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Revised: 11/14/2023] [Accepted: 11/17/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND Feeding intolerance (FI) is a significant concern in the care of preterm infants, impacting their growth and development. We previously reported that FI is linked to lower fecal calprotectin (FC) levels. This study aims to explore the postnatal dynamics and interplay between microbiota, metabolic profiles, and host immunity in preterm infants with and without FI. METHODS Infants with gestational age <32 weeks or birth weight <1500 g were enrolled at the Children's Hospital of Fudan University between January 2018 and October 2020. Weekly fecal samples were analyzed for bacterial profiling, metabolome, and calprotectin levels, exploring their longitudinal development and interrelationships. RESULTS Of the 118 very preterm infants studied, 48 showed FI. These infants experienced an interrupted microbial-immune trajectory, particularly at 3-4 weeks of age, marked by a reduced bacterial abundance, alpha diversity, and FC levels. Metabolic changes in FI were pronounced between 3 and 6 weeks. Pantothenic acid and two polyamine metabolites were closely associated with bacterial abundance and FC levels and negatively correlated with the duration to attain full enteral feeding. CONCLUSIONS FI infants demonstrated compromised microbiome-immune interactions, potentially influenced by specific metabolites. This research underscored the importance of early microbial and metabolic development in the pathogenesis of FI in very preterm infants.
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Affiliation(s)
- Luyang Hong
- Department of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China
| | - Yihuang Huang
- Department of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China
| | - Junyan Han
- Department of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China
| | - Shujuan Li
- Department of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China
| | - Lan Zhang
- Department of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China
| | - Siyuan Jiang
- Department of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China
| | - Qi Zhou
- Department of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China
| | - Xincheng Cao
- Department of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China
| | - Weiyin Yu
- Department of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China
| | - Yi Yang
- NHC Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China; (Y.Y.)
| | - Shangyu Hong
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China;
| | - Yufeng Zhou
- NHC Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China; (Y.Y.)
| | - Weili Yan
- Department of Clinical Epidemiology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China
| | - Yun Cao
- Department of Neonatology, Children’s Hospital of Fudan University, National Children’s Medical Center, Shanghai 201102, China
- NHC Key Laboratory of Neonatal Diseases, Fudan University, Shanghai 201102, China; (Y.Y.)
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Singh SV, Ganguly R, Jaiswal K, Yadav AK, Kumar R, Pandey AK. Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome: A comprehensive review. World J Clin Cases 2023; 11:4458-4476. [PMID: 37469740 PMCID: PMC10353503 DOI: 10.12998/wjcc.v11.i19.4458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2022] [Revised: 05/09/2023] [Accepted: 06/06/2023] [Indexed: 06/30/2023] Open
Abstract
Irritable bowel syndrome (IBS) is a chronic functional disorder which alters gastrointestinal (GI) functions, thus leading to compromised health status. Pathophysiology of IBS is not fully understood, whereas abnormal gut brain axis (GBA) has been identified as a major etiological factor. Recent studies are suggestive for visceral hyper-sensitivity, altered gut motility and dysfunctional autonomous nervous system as the main clinical abnormalities in IBS patients. Bidirectional signalling interactions among these abnormalities are derived through various exogenous and endogenous factors, such as microbiota population and diversity, microbial metabolites, dietary uptake, and psychological abnormalities. Strategic efforts focused to study these interactions including probiotics, antibiotics and fecal transplantations in normal and germ-free animals are clearly suggestive for the pivotal role of gut microbiota in IBS etiology. Additionally, neurotransmitters act as communication tools between enteric microbiota and brain functions, where serotonin (5-hydroxytryptamine) plays a key role in pathophysiology of IBS. It regulates GI motility, pain sense and inflammatory responses particular to mucosal and brain activity. In the absence of a better understanding of various interconnected crosstalks in GBA, more scientific efforts are required in the search of novel and targeted therapies for the management of IBS. In this review, we have summarized the gut microbial composition, interconnected signalling pathways and their regulators, available therapeutics, and the gaps needed to fill for a better management of IBS.
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Affiliation(s)
- Shiv Vardan Singh
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Risha Ganguly
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Kritika Jaiswal
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Aditya Kumar Yadav
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Ramesh Kumar
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
| | - Abhay K Pandey
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, Uttar Pradesh, India
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9
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Cheddadi R, Khandekar NN, Yeramilli V, Martin C. The impact of maternal stress on the development of necrotizing enterocolitis: A comprehensive review. Semin Pediatr Surg 2023:151324. [PMID: 37316382 DOI: 10.1016/j.sempedsurg.2023.151324] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Necrotizing Enterocolitis (NEC) is a devastating intestinal inflammatory disease with significant morbidity and mortality. Numerous predictors have been implicated in the development of NEC, with a relatively less emphasis on maternal factors. Pregnancy drives women into a new stage of life that increases their susceptibility to biological and psychological stress. Additionally, maternal stress during pregnancy has been linked to various complications that can negatively impact both the mother and the developing fetus. These detrimental effects are facilitated by various systemic modifications. Similarly, there is evidence from animal studies that suggest a relationship between maternal stress and the occurrence of NEC due to the alterations observed in neonates. In this review, we will (1) discuss the physiological and psychological burden of maternal stress and how it can be linked to NEC, (2) summarize various predictors and risk factors of NEC, and (3) discuss the most widely utilized animal models for assessing the effects of prenatal stress on offspring.
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Affiliation(s)
- Riadh Cheddadi
- Department of Surgery, Division of Pediatric Surgery, Children's of Alabama, University of Alabama at Birmingham, 1600 7th Ave. S., Lowder Building Suite 300, Birmingham, AL 35233, United States
| | | | - Venkata Yeramilli
- Department of Surgery, Division of Pediatric Surgery, Children's of Alabama, University of Alabama at Birmingham, 1600 7th Ave. S., Lowder Building Suite 300, Birmingham, AL 35233, United States
| | - Colin Martin
- Department of Surgery, Division of Pediatric Surgery, Children's of Alabama, University of Alabama at Birmingham, 1600 7th Ave. S., Lowder Building Suite 300, Birmingham, AL 35233, United States.
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10
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Bosnar LM, Shindler AE, Wood J, Patch C, Franks AE. Attempts to limit sporulation in the probiotic strain Bacillus subtilis BG01-4 TM through mutation accumulation and selection. Access Microbiol 2023; 5:acmi000419. [PMID: 37323944 PMCID: PMC10267654 DOI: 10.1099/acmi.0.000419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 03/16/2023] [Indexed: 06/17/2023] Open
Abstract
The use of bacterial spores in probiotics over viable loads of bacteria has many advantages, including the durability of spores, which allows spore-based probiotics to effectively traverse the various biochemical barriers present in the gastrointestinal tract. However, the majority of spore-based probiotics developed currently aim to treat adults, and there is a litany of differences between the adult and infant intestinal systems, including the immaturity and low microbial species diversity observed within the intestines of infants. These differences are only further exacerbated in premature infants with necrotizing enterocolitis (NEC) and indicates that what may be appropriate for an adult or even a healthy full-term infant may not be suited for an unhealthy premature infant. Complications from using spore-based probiotics for premature infants with NEC may involve the spores remaining dormant and adhering to the intestinal epithelia, the out-competing of commensal bacteria by spores, and most importantly the innate antibiotic resistance of spores. Also, the ability of Bacillus subtilis to produce spores under duress may result in less B. subtilis perishing within the intestines and releasing membrane branched-chain fatty acids. The isolate B. subtilis BG01-4TM is a proprietary strain developed by Vernx Biotechnology through accumulating mutations within the BG01-4TM genome in a serial batch culture. Strain BG01-4TM was provided as a non-spore-forming B. subtilis , but a positive sporulation status for BG01-4TM was confirmed through in vitro testing and suggested that selection for the sporulation defective genes could occur within an environment that would select against sporulation. The durability of key sporulation genes was ratified in this study, as the ability of BG01-4TM to produce spores was not eliminated by the attempts to select against sporulation genes in BG01-4TM by the epigenetic factors of high glucose and low pH. However, a variation in the genes in isolate BG01-4-8 involved in the regulation of sporulation is believed to have occurred during the mutation selection from the parent strain BG01-4TM. An alteration in selected sporulation regulation genes is expected to have occurred from BG01-4TM to BG01-4-8, with BG01-4-8 producing spores within 24 h, ~48 h quicker than BG01-4TM.
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Affiliation(s)
- Luke M. Bosnar
- Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, Victoria 3086, Australia
| | - Anya E. Shindler
- Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, Victoria 3086, Australia
| | - Jennifer Wood
- Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, Victoria 3086, Australia
| | - Craig Patch
- School of Allied Health, Human Services, and Sport, La Trobe University, Melbourne, Victoria 3086, Australia
- Vernx Pty Ltd, Level 17, 40 City Road, Southbank, Victoria 3066, Australia
| | - Ashley E. Franks
- Department of Physiology, Anatomy and Microbiology, School of Life Sciences, La Trobe University, Melbourne, Victoria 3086, Australia
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11
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Essock-Burns T, Lawhorn S, Wu L, McClosky S, Moriano-Gutierrez S, Ruby EG, McFall-Ngai MJ. Maturation state of colonization sites promotes symbiotic resiliency in the Euprymna scolopes-Vibrio fischeri partnership. MICROBIOME 2023; 11:68. [PMID: 37004104 PMCID: PMC10064550 DOI: 10.1186/s40168-023-01509-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Accepted: 03/05/2023] [Indexed: 06/18/2023]
Abstract
BACKGROUND Many animals and plants acquire their coevolved symbiotic partners shortly post-embryonic development. Thus, during embryogenesis, cellular features must be developed that will promote both symbiont colonization of the appropriate tissues, as well as persistence at those sites. While variation in the degree of maturation occurs in newborn tissues, little is unknown about how this variation influences the establishment and persistence of host-microbe associations. RESULTS The binary symbiosis model, the squid-vibrio (Euprymna scolopes-Vibrio fischeri) system, offers a way to study how an environmental gram-negative bacterium establishes a beneficial, persistent, extracellular colonization of an animal host. Here, we show that bacterial symbionts occupy six different colonization sites in the light-emitting organ of the host that have both distinct morphologies and responses to antibiotic treatment. Vibrio fischeri was most resilient to antibiotic disturbance when contained within the smallest and least mature colonization sites. We show that this variability in crypt development at the time of hatching allows the immature sites to act as a symbiont reservoir that has the potential to reseed the more mature sites in the host organ when they have been cleared by antibiotic treatment. This strategy may produce an ecologically significant resiliency to the association. CONCLUSIONS The data presented here provide evidence that the evolution of the squid-vibrio association has been selected for a nascent organ with a range of host tissue maturity at the onset of symbiosis. The resulting variation in physical and chemical environments results in a spectrum of host-symbiont interactions, notably, variation in susceptibility to environmental disturbance. This "insurance policy" provides resiliency to the symbiosis during the critical period of its early development. While differences in tissue maturity at birth have been documented in other animals, such as along the infant gut tract of mammals, the impact of this variation on host-microbiome interactions has not been studied. Because a wide variety of symbiosis characters are highly conserved over animal evolution, studies of the squid-vibrio association have the promise of providing insights into basic strategies that ensure successful bacterial passage between hosts in horizontally transmitted symbioses. Video Abstract.
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Affiliation(s)
- Tara Essock-Burns
- Kewalo Marine Laboratory, Pacific Biosciences Research Center, University of Hawai'i, Mānoa, Honolulu, HI, USA
- Present address: Carnegie Institution for Science, Division of Biosphere Sciences and Engineering, Pasadena, CA, USA
| | - Susannah Lawhorn
- Kewalo Marine Laboratory, Pacific Biosciences Research Center, University of Hawai'i, Mānoa, Honolulu, HI, USA
| | - Leo Wu
- Kewalo Marine Laboratory, Pacific Biosciences Research Center, University of Hawai'i, Mānoa, Honolulu, HI, USA
| | - Sawyer McClosky
- Kewalo Marine Laboratory, Pacific Biosciences Research Center, University of Hawai'i, Mānoa, Honolulu, HI, USA
| | - Silvia Moriano-Gutierrez
- Kewalo Marine Laboratory, Pacific Biosciences Research Center, University of Hawai'i, Mānoa, Honolulu, HI, USA
- Present address: Department of Fundamental Biology, University of Lausanne, Lausanne, Switzerland
| | - Edward G Ruby
- Kewalo Marine Laboratory, Pacific Biosciences Research Center, University of Hawai'i, Mānoa, Honolulu, HI, USA
- Present address: Carnegie Institution for Science, Division of Biosphere Sciences and Engineering, Pasadena, CA, USA
| | - Margaret J McFall-Ngai
- Kewalo Marine Laboratory, Pacific Biosciences Research Center, University of Hawai'i, Mānoa, Honolulu, HI, USA.
- Present address: Carnegie Institution for Science, Division of Biosphere Sciences and Engineering, Pasadena, CA, USA.
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12
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Du TT, Liu XC, He Y, Gao X, Liu ZZ, Wang ZL, Li LQ. Changes of gut microbiota and tricarboxylic acid metabolites may be helpful in early diagnosis of necrotizing enterocolitis: A pilot study. Front Microbiol 2023; 14:1119981. [PMID: 37007499 PMCID: PMC10050441 DOI: 10.3389/fmicb.2023.1119981] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 02/23/2023] [Indexed: 03/17/2023] Open
Abstract
PurposeWe aimed to explore the value of gut microbiota and tricarboxylic acid (TCA) metabolites in early diagnosis of necrotizing enterocolitis (NEC) among infants with abdominal manifestations.MethodsThirty-two preterm infants with abdominal manifestations at gestational age ≤ 34 weeks were included in the study and were divided into non-NEC (n = 16) and NEC (n = 16) groups. Faecal samples were collected when the infants were enrolled. The gut microbiota was analysed with high-throughput sequencing, and TCA metabolites were measured with multiple reaction monitoring (MRM) targeted metabolomics. Receiver operating characteristic (ROC) curves were generated to explore the predictive value of the obtained data.ResultsThere was no significant difference in alpha diversity or beta diversity between the two groups (p > 0.05). At the phylum level, Proteobacteria increased, and Actinomycetota decreased in the NEC group (p < 0.05). At the genus level, Bifidobacterium and Lactobacillaceae decreased significantly, and at the species level, unclassified Staphylococcus, Lactobacillaceae and Bifidobacterium animalis subsp. lactis decreased in the NEC group (p < 0.05). Further Linear discriminant analysis effect sizes (LEfSe) analysis showed that the change in Proteobacteria at the phylum level and Lactobacillaceae and Bifidobacterium at the genus level scored higher than 4. The concentrations of succinate, L-malic acid and oxaloacetate in the NEC group significantly increased (p < 0.05), and the areas under the ROC curve for these metabolites were 0.6641, 0.7617, and 0.7344, respectively.ConclusionDecreased unclassified Staphylococcus, Lactobacillaceae and Bifidobacterium animalis subsp. lactis at the species level as well as the increase in the contents of some TCA metabolites, including succinate, L-malic acid and oxaloacetate, have potential value for the early diagnosis of NEC.
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Affiliation(s)
- Ting-Ting Du
- Neonatal Diagnosis and Treatment Centre of Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Xiao-Chen Liu
- Neonatal Diagnosis and Treatment Centre of Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Yu He
- Neonatal Diagnosis and Treatment Centre of Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Xiong Gao
- Neonatal Diagnosis and Treatment Centre of Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Zhen-Zhen Liu
- Neonatal Diagnosis and Treatment Centre of Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Zheng-Li Wang
- Neonatal Diagnosis and Treatment Centre of Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
| | - Lu-Quan Li
- Neonatal Diagnosis and Treatment Centre of Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China
- Jiangxi Hospital Affiliated Children’s Hospital of Chongqing Medical University, Nanchang, China
- *Correspondence: Lu-Quan Li,
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13
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Comparison and Investigation of Exosomes from Human Amniotic Fluid Stem Cells and Human Breast Milk in Alleviating Neonatal Necrotizing Enterocolitis. Stem Cell Rev Rep 2022; 19:754-766. [PMID: 36385400 PMCID: PMC10070207 DOI: 10.1007/s12015-022-10470-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/18/2022] [Indexed: 11/17/2022]
Abstract
Abstract
In view of the devastating impact of neonatal necrotizing enterocolitis (NEC) on newborns, the research on its intervention is particularly important. Although exosomes from human amniotic fluid stem cells (AFSC) and human breast milk (HBM) can protect against NEC, their mechanisms remain unclear. Here, we intend to compare the intervention effects of two types of exosomes on NEC mouse model and reveal their respective regulatory mechanisms. In general, both AFSC-derived exosomes (AFSC-exos) and HBM-derived exosomes (HBM- exos) can alleviate NEC- associated intestinal injury, significantly reduce NEC score, and reduce systemic and ileal inflammation and NEC related brain injury during experimental NEC. However, the mode and mechanism of action of the two sources of exosomes were not identical. In vivo, the number of ileal crypts was more significantly restored after HBM-exos intervention than AFSC-exos, and in vitro, HBM-exos preferentially inhibited the inflammatory response of intestinal epithelial cells (IECs), whereas AFSC-exos preferentially regulated the migration of IECs. Mechanistically, GO and KEGG analyses revealed the different therapeutic mechanisms of AFSC-exos and HBM-exos in NEC. Taken together, our results illustrate that AFSC-exos and HBM-exos reduce the severity of experimental NEC and intestinal damage through different mechanisms, supporting the potential of cell-free or breast milk free exosome therapy for NEC.
Graphical Abstract
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14
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Cerdó T, García-Santos JA, Rodríguez-Pöhnlein A, García-Ricobaraza M, Nieto-Ruíz A, G. Bermúdez M, Campoy C. Impact of Total Parenteral Nutrition on Gut Microbiota in Pediatric Population Suffering Intestinal Disorders. Nutrients 2022; 14:4691. [PMID: 36364953 PMCID: PMC9658482 DOI: 10.3390/nu14214691] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 11/01/2022] [Accepted: 11/04/2022] [Indexed: 08/10/2023] Open
Abstract
Parenteral nutrition (PN) is a life-saving therapy providing nutritional support in patients with digestive tract complications, particularly in preterm neonates due to their gut immaturity during the first postnatal weeks. Despite this, PN can also result in several gastrointestinal complications that are the cause or consequence of gut mucosal atrophy and gut microbiota dysbiosis, which may further aggravate gastrointestinal disorders. Consequently, the use of PN presents many unique challenges, notably in terms of the potential role of the gut microbiota on the functional and clinical outcomes associated with the long-term use of PN. In this review, we synthesize the current evidence on the effects of PN on gut microbiome in infants and children suffering from diverse gastrointestinal diseases, including necrotizing enterocolitis (NEC), short bowel syndrome (SBS) and subsequent intestinal failure, liver disease and inflammatory bowel disease (IBD). Moreover, we discuss the potential use of pre-, pro- and/or synbiotics as promising therapeutic strategies to reduce the risk of severe gastrointestinal disorders and mortality. The findings discussed here highlight the need for more well-designed studies, and harmonize the methods and its interpretation, which are critical to better understand the role of the gut microbiota in PN-related diseases and the development of efficient and personalized approaches based on pro- and/or prebiotics.
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Affiliation(s)
- Tomás Cerdó
- Maimonides Institute for Research in Biomedicine of Córdoba (IMIBIC), Reina Sofia University Hospital, University of Córdoba, 14004 Córdoba, Spain
| | - José Antonio García-Santos
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Anna Rodríguez-Pöhnlein
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - María García-Ricobaraza
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Ana Nieto-Ruíz
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Mercedes G. Bermúdez
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
| | - Cristina Campoy
- EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, 18016 Granada, Spain
- Department of Paediatrics, School of Medicine, University of Granada, Avda. Investigación 11, 18016 Granada, Spain
- Instituto de Investigación Biosanitaria Ibs-GRANADA, Health Sciences Technological Park, 18012 Granada, Spain
- Spanish Network of Biomedical Research in Epidemiology and Public Health (CIBERESP), Granada’s Node, Carlos III Health Institute, Avda. Monforte de Lemos 5, 28028 Madrid, Spain
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15
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Balasundaram M, Land R, Miller S, Profit J, Porter M, Arnold C, Sivakumar D. Increasing early exposure to mother's own milk in premature newborns. J Perinatol 2022; 42:1126-1134. [PMID: 35396577 DOI: 10.1038/s41372-022-01376-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 03/02/2022] [Accepted: 03/17/2022] [Indexed: 11/09/2022]
Abstract
OBJECTIVE Increase the proportion of ≤33 weeks newborns exposed to mother's own milk (MOM) oral care by 12 h of age by 20% over 2 years to support a healthier microbiome. STUDY DESIGN We implemented interventions to support early expression of colostrum and reliable delivery of resultant MOM to premature newborns. Statistical process control charts were used to track progress and provide feedback to staff. Proportions of newborns exposed to MOM by 12 h were compared relative to baseline. RESULTS There were 46, 66, and 46 newborns in the baseline, implementation, and sustainability periods, respectively. The primary outcome improved from 48% to 61% in the implementation period (relative change 1.27, 95% CI 0.89, 1.81, p = 0.2), to 69% in sustainability period (relative to baseline 1.45, 95% CI 1.02, 2.08, p = 0.03). CONCLUSION An interdisciplinary team-based, multicycle, quality improvement intervention resulted in increased rates of early exposure to MOM.
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Affiliation(s)
- Malathi Balasundaram
- Division of Neonatal & Developmental Medicine, Stanford University School of Medicine, Palo Alto, CA, USA. .,Neonatal Intensive Care Unit, El Camino Health, Mountain View, CA, USA.
| | - Rachel Land
- Division of Neonatal & Developmental Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.,Neonatal Intensive Care Unit, El Camino Health, Mountain View, CA, USA
| | - Stephanie Miller
- Division of Neonatal & Developmental Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.,Neonatal Intensive Care Unit, El Camino Health, Mountain View, CA, USA
| | - Jochen Profit
- Division of Neonatal & Developmental Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.,California Perinatal Quality Care Collaborative, Palo Alto, CA, USA
| | - Melinda Porter
- Neonatal Intensive Care Unit, El Camino Health, Mountain View, CA, USA
| | - Cody Arnold
- Division of Neonatal & Developmental Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.,Neonatal Intensive Care Unit, El Camino Health, Mountain View, CA, USA
| | - Dharshi Sivakumar
- Division of Neonatal & Developmental Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.,Neonatal Intensive Care Unit, El Camino Health, Mountain View, CA, USA
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16
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Antibacterial and anti-inflammatory effects of Lactobacillus reuteri in its biofilm state contribute to its beneficial effects in a rat model of experimental necrotizing enterocolitis. J Pediatr Surg 2022; 57:1382-1390. [PMID: 34657737 DOI: 10.1016/j.jpedsurg.2021.09.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 08/25/2021] [Accepted: 09/02/2021] [Indexed: 01/26/2023]
Abstract
INTRODUCTION Necrotizing enterocolitis (NEC) remains a significant surgical emergency in neonates. We have demonstrated the efficacy of Lactobacillus reuteri (Lr) in protecting against experimental NEC when administered as a biofilm by incubation with maltose loaded dextranomer microspheres. Lr possesses antimicrobial and anti-inflammatory properties. We developed mutant strains of Lr to examine the importance of its antimicrobial and anti-inflammatory properties in protecting the intestines from NEC. METHODS Premature rat pups were exposed to hypoxia/hypothermia/hypertonic feeds to induce NEC. To examine the importance of antimicrobial reuterin and anti-inflammatory histamine, pups received either native or mutant forms of Lr, in either its planktonic or biofilm states, prior to induction of NEC. Intestinal histology was examined upon sacrifice. RESULTS Compared to no treatment, administration of a single dose of Lr in its biofilm state significantly decreased the incidence of NEC (67% vs. 18%, p < 0.0001), whereas Lr in its planktonic state had no significant effect. Administration of reuterin-deficient or histamine-deficient forms of Lr, in either planktonic or biofilm states, resulted in significant loss of efficacy. CONCLUSION Antimicrobial and anti-inflammatory effects of Lr contribute to its beneficial effects against NEC. This suggests that both infectious and inflammatory components contribute to the etiology of NEC.
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17
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Guo C, Shi Y. Editorial: Intestinal Microbiota in the Pathogenesis and Management of Necrotizing Enterocolitis in Preterm Infants. Front Pediatr 2022; 10:837925. [PMID: 35252069 PMCID: PMC8892253 DOI: 10.3389/fped.2022.837925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 01/03/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
- Chunbao Guo
- Department of Pediatric General Surgery, Children's Hospital of Chongqing Medical University, Chongqing, China.,Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.,China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Yuan Shi
- Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.,China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China.,Department of Neonatology, Chongqing Medical University, Chongqing, China
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18
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Jeziorczak PM, Frenette RS, Aprahamian CJ. Lack of Enteral Feeding Associated with Mortality in Prematurity and Necrotizing Enterocolitis. J Surg Res 2021; 270:266-270. [PMID: 34715538 DOI: 10.1016/j.jss.2021.09.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 08/24/2021] [Accepted: 09/21/2021] [Indexed: 11/25/2022]
Abstract
BACKGROUND Necrotizing Enterocolitis (NEC) remains a significant cause of morbidity and mortality. Recently, there has been an increased recognition of the importance of intestinal immunity and the associations with antibiotics and enteral feeds in the pathophysiology of NEC. The primary purpose of this study is to examine the association of enteral feeds on the survival of premature neonates with NEC. MATERIAL AND METHODS A retrospective review using the Vermont Oxford Network for a Level IV NICU from January 1, 2013 through December 31, 2019 was performed. All neonates had a gestational age between 22 to 29 weeks, weighed at least 300 grams (n = 653), had a reported enteral feed status and were treated for NEC (n = 43). Data analysis utilized two-tailed t-tests for NEC and infection rates then Fisher's exact tests for survival status. RESULTS The incidence of NEC in the population was 6.6% (43/653). Of the 43 neonates treated for NEC, 27 were enterally fed, while the other 16 were not. All 27 neonates with NEC that were able to achieve enteral feeds survived and had an infection rate of 22.2%. Meanwhile, all 16 neonates with NEC that were unable to achieve enteral feeds died and had an infection rate of 62.5%. CONCLUSIONS There is a significant association between enteral feeds and NEC, survival, and infection rates in premature neonates. These findings support the importance of intestinal immunity and the microbiota in NEC. Given the limitations of the retrospective review, the profound survival advantage with enteral feeds reinforces the need for further study.
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Affiliation(s)
- Paul M Jeziorczak
- OSF Healthcare- Children's Hospital of Illinois, Peoria, IL; University of Illinois College of Medicine at Peoria, Peoria, IL
| | - Riley S Frenette
- OSF Healthcare- Children's Hospital of Illinois, Peoria, IL; A.T. Still University-Kirksville College of Osteopathic Medicine, Kirksville, MO.
| | - Charles J Aprahamian
- OSF Healthcare- Children's Hospital of Illinois, Peoria, IL; University of Illinois College of Medicine at Peoria, Peoria, IL
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19
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Cassir N, Belkacemi S, Ballouche M, Khelaifia S, La Scola B. Evaluation of Culture Top transport systems for assessing the bacterial diversity of microbiota by culturomics as compared to a routine transport system. J Med Microbiol 2021; 70. [PMID: 34665113 DOI: 10.1099/jmm.0.001411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
In recent years, metagenomics and then culturomics, which consists of the multiplication of media and culture conditions and the rapid identification of all bacterial colonies, have generated renewed interest in the human microbiota, and diseases associated with modifications in its composition in particular. The sample transport media included in diverse swab transport systems and the storage conditions are among the factors that influence the results of the culturomics. In this study, we compared the results of culturomics from paired skin, oral and rectal swabs from intensive care unit (ICU) patients using Culture Top sample transport medium as compared to our routine one. From 152 clinical samples, we were able to isolate and identify 45 600 colonies, belonging to 338 different bacterial species. The transport system Culture Top identified 282 different bacterial species, while 244 were identified by our routine system. Of these, 188 different bacterial species were commonly identified using both transport systems, while 94 (27.8 %) and 56 (16.5 %) were only identified using Culture Top and our routine system, respectively (P<0.001), but there was no significant difference in bacterial diversity at the genus or phylum level, or in terms of their type of respiration and cell wall. In conclusion, the Culture Top transport system appears to be complementary to our routine system, although it seems slightly superior in terms of isolated bacterial species.
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Affiliation(s)
- Nadim Cassir
- Aix-Marseille Univ, IRD, APHM, MEPHI, Marseille, France.,Institut Hospitalo-Universitaire Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005 Marseillle, France
| | | | | | - Saber Khelaifia
- Aix-Marseille Univ, IRD, APHM, MEPHI, Marseille, France.,Institut Hospitalo-Universitaire Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005 Marseillle, France
| | - Bernard La Scola
- Aix-Marseille Univ, IRD, APHM, MEPHI, Marseille, France.,Institut Hospitalo-Universitaire Méditerranée Infection, 19-21 Boulevard Jean Moulin, 13005 Marseillle, France
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20
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Thomson P, Núñez P, Quera R, Bay C. Gastrointestinal microbiome, what is behind faecal microbiota transplantation? New Microbes New Infect 2021; 42:100898. [PMID: 34168881 PMCID: PMC8207221 DOI: 10.1016/j.nmni.2021.100898] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 05/06/2021] [Accepted: 05/09/2021] [Indexed: 12/19/2022] Open
Abstract
The intestinal microbiota is made up of billions of microorganisms that coexist in an organised ecosystem, where strict and facultative anaerobic bacteria predominate. The alteration or imbalance of these microorganisms, known as dysbiosis, can be associated with both gastrointestinal and extraintestinal diseases. Based on a review of the literature, the intestinal microbiota is described in its state of health, the changes associated with some gastrointestinal diseases and the potential role that faecal microbiota transplantation has in the reestablishment of an altered ecosystem. Undoubtedly, the information revealed makes us reflect on the indication of faecal microbiota transplantation in various pathologies of intestinal origin. However, to ensure the efficacy and safety of this therapy, more studies are needed to obtain more evidence.
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Affiliation(s)
- P. Thomson
- Veterinarian School of Medicine, Faculty of Life Science, Andrés Bello University, Avenida República 440, Santiago, Chile
| | - P. Núñez
- Department of Gastroenterology, Hospital San Juan De Dios – University of Chile, Huérfanos 3255, Santiago, Chile
- Gastroenterology Department, Clínica Universidad de los Andes, Avda. Plaza 2501, Chile
| | - R. Quera
- Gastroenterology Department, Clínica Universidad de los Andes, Avda. Plaza 2501, Chile
| | - C. Bay
- Department of Pediatrics, Medicine School, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, Chile
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21
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Maternal and Neonatal Oral Microbiome Developmental Patterns and Correlated Factors: A Systematic Review-Does the Apple Fall Close to the Tree? INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18115569. [PMID: 34071058 PMCID: PMC8197112 DOI: 10.3390/ijerph18115569] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 05/16/2021] [Accepted: 05/21/2021] [Indexed: 12/21/2022]
Abstract
(1) Background: The purpose of the study was to comprehensively analyze the relationship between the mother’s oral microbiome, modes of delivery and feeding, and the formation of the newborn child’s oral microbiome. (2) Methods: This systematic review included a search through MEDLINE (PubMed) database (from 2010 to July 2020). Research was registered in PROSPERO under the number CRD42021241044. (3) Results: Of the 571 studies, 11 met the inclusion criteria. Included studies were classified according to (i) child’s delivery mode, (ii) maternal exposure to antibiotics and disinfectants, and (iii) feeding type. (4) Conclusions: The interpretation of these papers shows that the type of delivery, maternal exposure to disinfectants and antibiotics during delivery, maternal health classed as overweight, gestational diabetes mellitus, and feeding type are correlated to changes in the maternal and neonatal early oral microbiomes, based on the analysis provided in this systematic review. Because no evidence exists regarding the impact of maternal diet and maternal oral health on the establishment and development of the early oral newborn microbiome, more studies are needed to deepen the knowledge and understanding of the subject and develop preventive and therapeutic strategies of support to pregnant women.
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22
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Sampah MES, Hackam DJ. Prenatal Immunity and Influences on Necrotizing Enterocolitis and Associated Neonatal Disorders. Front Immunol 2021; 12:650709. [PMID: 33968047 PMCID: PMC8097145 DOI: 10.3389/fimmu.2021.650709] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2021] [Accepted: 04/06/2021] [Indexed: 12/14/2022] Open
Abstract
Prior to birth, the neonate has limited exposure to pathogens. The transition from the intra-uterine to the postnatal environment initiates a series of complex interactions between the newborn host and a variety of potential pathogens that persist over the first few weeks of life. This transition is particularly complex in the case of the premature and very low birth weight infant, who may be susceptible to many disorders as a result of an immature and underdeveloped immune system. Chief amongst these disorders is necrotizing enterocolitis (NEC), an acute inflammatory disorder that leads to necrosis of the intestine, and which can affect multiple systems and have the potential to result in long term effects if the infant is to survive. Here, we examine what is known about the interplay of the immune system with the maternal uterine environment, microbes, nutritional and other factors in the pathogenesis of neonatal pathologies such as NEC, while also taking into consideration the effects on the long-term health of affected children.
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Affiliation(s)
| | - David J. Hackam
- Division of Pediatric Surgery, Department of Surgery, Johns Hopkins University School of Medicine , Baltimore, MD, United States
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23
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Antibiotics Modulate Intestinal Regeneration. BIOLOGY 2021; 10:biology10030236. [PMID: 33808600 PMCID: PMC8003396 DOI: 10.3390/biology10030236] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 03/09/2021] [Accepted: 03/17/2021] [Indexed: 02/02/2023]
Abstract
Simple Summary The impact of the microbial community on host’s biological functions has uncovered the potential outcomes of antibiotics on host physiology, introducing the caveats of the antibiotic usage. Within animals, the digestive function is closely related to the microorganisms that inhabit this organ. The proper maintenance of the digestive system requires constant regeneration. These processes vary from self-renewal of some cells or tissues in some species to the complete regeneration of the organ in others. Whether antibiotics influence digestive organ regeneration remains unknown. We employ the sea cucumber, Holothuria glaberrima, for its capacity to regenerate the whole intestine after ejection from its internal cavity. We explored the antibiotics’ effects on several intestinal regeneration processes. In parallel, we studied the effect of antibiotics on the animals’ survival, toxicity, and gut bacteria growth. Our results show that tested antibiotics perturbed key cellular processes that occur during intestinal regeneration. Moreover, this happens at doses that inhibited bacteria growth but did not alter holothurian’s metabolic activity. We propose that antibiotics can perturb the cellular events of intestinal regeneration via their impact on the microbiota. These results highlight H. glaberrima as a promising model to study the importance of the microbiota during organ regeneration. Abstract The increased antibiotics usage in biomedical and agricultural settings has been well documented. Antibiotics have now been shown to exert effects outside their purposive use, including effects on physiological and developmental processes. We explored the effect of various antibiotics on intestinal regeneration in the sea cucumber Holothuria glaberrima. For this, holothurians were eviscerated and left to regenerate for 10 days in seawater with different penicillin/streptomycin-based cocktails (100 µg/mL PS) including: 100 µg/mL kanamycin (KPS), 5 µg/mL vancomycin (VPS), and 4 µg/mL (E4PS) or 20 µg/mL (E20PS) erythromycin. Immunohistological and histochemical analyses were performed to analyze regenerative processes, including rudiment size, extracellular matrix (ECM) remodeling, cell proliferation, and muscle dedifferentiation. A reduction in muscle dedifferentiation was observed in all antibiotic-treated animals. ECM remodeling was decreased by VPS, E4PS, and E20PS treatments. In addition, organisms subjected to E20PS displayed a significant reduction in the size of their regenerating rudiments while VPS exposure altered cell proliferation. MTT assays were used to discard the possibility that the antibiotics directly affect holothurian metabolic activity while bacterial cultures were used to test antibiotic effects on holothurian enteric microbiota. Our results demonstrate a negative effect on intestinal regeneration and strongly suggest that these effects are due to alterations in the microbial community.
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Al-Hadidi A, Navarro J, Goodman SD, Bailey MT, Besner GE. Lactobacillus reuteri in Its Biofilm State Improves Protection from Experimental Necrotizing Enterocolitis. Nutrients 2021; 13:nu13030918. [PMID: 33809097 PMCID: PMC8000340 DOI: 10.3390/nu13030918] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/09/2021] [Accepted: 03/10/2021] [Indexed: 12/11/2022] Open
Abstract
Necrotizing enterocolitis (NEC) is a devastating disease predominately found in premature infants that is associated with significant morbidity and mortality. Despite decades of research, medical management with broad spectrum antibiotics and bowel rest has remained relatively unchanged, with no significant improvement in patient outcomes. The etiology of NEC is multi-factorial; however, gastrointestinal dysbiosis plays a prominent role in a neonate's vulnerability to and development of NEC. Probiotics have recently emerged as a new avenue for NEC therapy. However, current delivery methods are associated with potential limitations, including the need for at least daily administration in order to obtain any improvement in outcomes. We present a novel formulation of enterally delivered probiotics that addresses the current limitations. A single enteral dose of Lactobacillus reuteri delivered in a biofilm formulation increases probiotic survival in acidic gastric conditions, increases probiotic adherence to gastrointestinal epithelial cells, and reduces the incidence, severity, and neurocognitive sequelae of NEC in experimental models.
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Affiliation(s)
- Ameer Al-Hadidi
- Department of Pediatric Surgery, Nationwide Children’s Hospital, The Ohio State University College of Medicine, Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA;
| | - Jason Navarro
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA; (J.N.); (S.D.G.); (M.T.B.)
| | - Steven D. Goodman
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA; (J.N.); (S.D.G.); (M.T.B.)
| | - Michael T. Bailey
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA; (J.N.); (S.D.G.); (M.T.B.)
| | - Gail E. Besner
- Department of Pediatric Surgery, Nationwide Children’s Hospital, The Ohio State University College of Medicine, Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA;
- Correspondence: ; Tel.: +1-614-722-3914
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25
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Gut microbes and health. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 44:519-535. [PMID: 33652061 DOI: 10.1016/j.gastrohep.2021.01.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 01/20/2021] [Accepted: 01/24/2021] [Indexed: 12/12/2022]
Abstract
The human body is populated by myriads of microorganisms throughout its surface and in the cavities connected to the outside. The microbial colonisers of the intestine (microbiota) are a functional and non-expendable part of the human organism: they provide genes (microbiome) and additional functions to the resources of our species and participate in multiple physiological processes (somatic development, nutrition, immunity, etc.). Some chronic non-communicable diseases of developed society (atopias, metabolic syndrome, inflammatory diseases, cancer and some behaviour disorders) are associated with dysbiosis: loss of species richness in the intestinal microbiota and deviation from the ancestral microbial environment. Changes in the vertical transmission of the microbiome, the use of antiseptics and antibiotics, and dietary habits in industrialised society appear to be at the origin of dysbiosis. Generating and maintaining diversity in the microbiota is a new clinical target for health promotion and disease prevention.
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26
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Cassir N, Grandvuillemin I, Boxberger M, Jardot P, Boubred F, La Scola B. Case Report: Clostridium neonatale Bacteremia in a Preterm Neonate With Necrotizing Enterocolitis. Front Pediatr 2021; 9:771467. [PMID: 34926348 PMCID: PMC8674942 DOI: 10.3389/fped.2021.771467] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 10/28/2021] [Indexed: 11/13/2022] Open
Abstract
Necrotizing enterocolitis is a life-threatening acquired gastrointestinal disorder among preterm neonates and is associated with a high mortality rate and long-term neurodevelopmental morbidity. No etiologic agent has been definitively established; nonetheless, the most implicated bacteria include members of the Clostridium genus. We reported here on a case of Clostridium neonatale bacteremia in a preterm neonate with necrotizing enterocolitis, providing more information regarding the potential role of this bacterium in pathogenesis of necrotizing enterocolitis. We emphasized the sporulating form of C. neonatale that confers resistance to disinfectants usually applied for the hospital environmental cleaning. Further works are needed to establish the causal relationship between the occurrence of NEC and the isolation of C. neonatale, with promising perspectives in terms of diagnostic and therapeutic management.
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Affiliation(s)
- Nadim Cassir
- Department of Clinical Microbiology, Aix Marseille Université, Institut de Recherche pour le Développement, Assistance Publique des Hôpitaux de Marseille, Microbes, Evolution, Phylogénie et Infection, Marseille, France.,Institut Hospitalo-Universitaire Méditerranée Infection, Marseillle, France
| | - Isabelle Grandvuillemin
- Department of Neonatology, Hôpital La Conception, Assistance Publique des Hôpitaux de Marseille, AMU, Marseille, France
| | - Manon Boxberger
- Department of Clinical Microbiology, Aix Marseille Université, Institut de Recherche pour le Développement, Assistance Publique des Hôpitaux de Marseille, Microbes, Evolution, Phylogénie et Infection, Marseille, France.,Institut Hospitalo-Universitaire Méditerranée Infection, Marseillle, France
| | - Priscilla Jardot
- Department of Clinical Microbiology, Aix Marseille Université, Institut de Recherche pour le Développement, Assistance Publique des Hôpitaux de Marseille, Microbes, Evolution, Phylogénie et Infection, Marseille, France.,Institut Hospitalo-Universitaire Méditerranée Infection, Marseillle, France
| | - Farid Boubred
- Department of Neonatology, Hôpital La Conception, Assistance Publique des Hôpitaux de Marseille, AMU, Marseille, France.,Neonatal Unit, C2 VN, Hospital University La Conception, Assistance Publique des Hôpitaux de Marseille, AMU, Marseille, France
| | - Bernard La Scola
- Department of Clinical Microbiology, Aix Marseille Université, Institut de Recherche pour le Développement, Assistance Publique des Hôpitaux de Marseille, Microbes, Evolution, Phylogénie et Infection, Marseille, France.,Institut Hospitalo-Universitaire Méditerranée Infection, Marseillle, France
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27
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Cost-effectiveness of probiotics for necrotizing enterocolitis prevention in very low birth weight infants. J Perinatol 2020; 40:1652-1661. [PMID: 32811974 DOI: 10.1038/s41372-020-00790-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 07/22/2020] [Accepted: 08/07/2020] [Indexed: 11/09/2022]
Abstract
OBJECTIVE To examine the cost-effectiveness of prophylactic probiotics on necrotizing enterocolitis (NEC) prevention in very low birth weight (VLBW) infants. STUDY DESIGN We built a decision-analytic model using TreeAge. Effectiveness was assessed using quality-adjusted life-years (QALY). Primary outcome was an incremental cost-effectiveness ratio (ICER) expressed as cost per QALY gained. Costs were expressed in 2017 US dollars. Deterministic and probabilistic sensitivity analyses (SA) were performed. RESULTS For the base case analysis, the ICER of probiotics versus no probiotics for the prevention of NEC in VLBW infants was $1868/QALY. SA revealed that probiotics became cost-saving at a NEC rate of 6.5% and higher or with incremental NEC cost of $37,500 or higher. CONCLUSIONS Our model demonstrated that prophylactic probiotics were a cost-effective strategy in NEC reduction. SA confirmed that the model is customizable to various clinical settings and thus, can aid in understanding the economic impact of this intervention.
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28
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Elvers KT, Wilson VJ, Hammond A, Duncan L, Huntley AL, Hay AD, van der Werf ET. Antibiotic-induced changes in the human gut microbiota for the most commonly prescribed antibiotics in primary care in the UK: a systematic review. BMJ Open 2020; 10:e035677. [PMID: 32958481 PMCID: PMC7507860 DOI: 10.1136/bmjopen-2019-035677] [Citation(s) in RCA: 135] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 06/12/2020] [Accepted: 07/02/2020] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE The gut microbiota influences many aspects of human health. We investigated the magnitude and duration of changes in gut microbiota in response to antibiotics commonly prescribed in UK primary care. METHODS We searched MEDLINE, EMBASE and AMED, all years up to May 2020 including all study designs, collecting and analysing data on the effect of antibiotics prescribed for respiratory and urinary tract infections. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane standard methods. Risk of bias was evaluated using the Critical Appraisal Skills Programme. Narrative synthesis was used to report the themes emerging from the data. MAIN OUTCOME MEASURES Primary outcomes were antibiotic-induced changes in the composition and/or diversity of the gut microbiota. Secondary outcome was the time for the microbiota to return to baseline. RESULTS Thirty-one articles with low or unclear risk of bias showed that antibiotics impact the gut microbiota by causing rapid and diminished levels of bacterial diversity and changes in relative abundances. After cessation of treatment, gut bacteria recover, in most individuals, to their baseline state within a few weeks. Some studies suggested longer term effects from 2 to 6 months. Considerable heterogeneity in methodology makes the studies prone to biases and other confounding factors. Doxycycline was associated with a marked short-term decrease in Bifidobacterium diversity. Clarithromycin decreased the populations of Enterobacteria, and the anaerobic bacteria Bifidobacterium sp and Lactobacillus sp in numbers and diversity for up to 5 weeks. Phenoxymethylpenicillin, nitrofurantoin and amoxicillin had very little effect on the gut microbiome. CONCLUSIONS Despite substantial heterogeneity of the studies and small sample sizes, there is evidence that antibiotics commonly used in primary care influence the composition of the gastrointestinal microbiota. Larger population-based studies are needed to fully understand how antibiotics modulate the microbiota, and to determine if these are associated with (longer term) health consequences. PROSPERO REGISTRATION NUMBER CRD42017073750.
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Affiliation(s)
- Karen T Elvers
- Centre for Academic Primare Care & NIHR Health Protection Research Unit in Behavioural Science and Evaluation, Bristol Medical School, University of Bristol, Bristol, UK
| | - Victoria J Wilson
- Centre of Academic Primary Care, Bristol Medical School, University of Bristol, Bristol, UK
| | - Ashley Hammond
- Centre of Academic Primary Care, Bristol Medical School, University of Bristol, Bristol, UK
| | - Lorna Duncan
- Centre of Academic Primary Care, Bristol Medical School, University of Bristol, Bristol, UK
| | - Alyson L Huntley
- Centre of Academic Primary Care, Bristol Medical School, University of Bristol, Bristol, UK
| | - Alastair D Hay
- Centre of Academic Primary Care, Bristol Medical School, University of Bristol, Bristol, UK
| | - Esther T van der Werf
- Centre of Academic Primary Care, Bristol Medical School, University of Bristol, Bristol, UK
- Department of Integrative Medicine, Louis Bolk Institute, Bunnik, The Netherlands
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29
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Alcon-Giner C, Dalby MJ, Caim S, Ketskemety J, Shaw A, Sim K, Lawson MA, Kiu R, Leclaire C, Chalklen L, Kujawska M, Mitra S, Fardus-Reid F, Belteki G, McColl K, Swann JR, Kroll JS, Clarke P, Hall LJ. Microbiota Supplementation with Bifidobacterium and Lactobacillus Modifies the Preterm Infant Gut Microbiota and Metabolome: An Observational Study. CELL REPORTS MEDICINE 2020; 1:100077. [PMID: 32904427 PMCID: PMC7453906 DOI: 10.1016/j.xcrm.2020.100077] [Citation(s) in RCA: 130] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 04/28/2020] [Accepted: 07/31/2020] [Indexed: 12/11/2022]
Abstract
Supplementation with members of the early-life microbiota as “probiotics” is increasingly used in attempts to beneficially manipulate the preterm infant gut microbiota. We performed a large observational longitudinal study comprising two preterm groups: 101 infants orally supplemented with Bifidobacterium and Lactobacillus (Bif/Lacto) and 133 infants non-supplemented (control) matched by age, sex, and delivery method. 16S rRNA gene profiling on fecal samples (n = 592) showed a predominance of Bifidobacterium and a lower abundance of pathobionts in the Bif/Lacto group. Metabolomic analysis showed higher fecal acetate and lactate and a lower fecal pH in the Bif/Lacto group compared to the control group. Fecal acetate positively correlated with relative abundance of Bifidobacterium, consistent with the ability of the supplemented Bifidobacterium strain to metabolize human milk oligosaccharides into acetate. This study demonstrates that microbiota supplementation is associated with a Bifidobacterium-dominated preterm microbiota and gastrointestinal environment more closely resembling that of full-term infants.
Bifidobacterium dominates the gut microbiota in supplemented preterm infants Supplemented preterm infants have lower abundance of potential pathobionts Metabolomic analysis show higher fecal acetate and lower pH in supplemented infants In vitro and genomic analysis confirm HMO metabolism in Bifidobacterium supplement
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Affiliation(s)
- Cristina Alcon-Giner
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Matthew J. Dalby
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Shabhonam Caim
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Jennifer Ketskemety
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Alex Shaw
- Department of Medicine, Section of Pediatrics, Imperial College London, London, UK
| | - Kathleen Sim
- Department of Medicine, Section of Pediatrics, Imperial College London, London, UK
| | - Melissa A.E. Lawson
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Raymond Kiu
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Charlotte Leclaire
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Lisa Chalklen
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Magdalena Kujawska
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
| | - Suparna Mitra
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
- Leeds Institute of Medical Research, University of Leeds, Leeds, UK
| | - Fahmina Fardus-Reid
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
| | - Gustav Belteki
- Neonatal Intensive Care Unit, The Rosie Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Katherine McColl
- Neonatal Intensive Care Unit, Norfolk and Norwich University Hospital, Norwich, UK
| | - Jonathan R. Swann
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
| | - J. Simon Kroll
- Department of Medicine, Section of Pediatrics, Imperial College London, London, UK
| | - Paul Clarke
- Neonatal Intensive Care Unit, Norfolk and Norwich University Hospital, Norwich, UK
- Norwich Medical School, University of East Anglia, Norwich, UK
| | - Lindsay J. Hall
- Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
- Norwich Medical School, University of East Anglia, Norwich, UK
- Chair of Intestinal Microbiome, School of Life Sciences, Technical University of Munich, Freising, Germany
- ZIEL – Institute for Food & Health, Technical University of Munich, Freising, Germany
- Corresponding author
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30
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Interactions of Symbiotic Partners Drive the Development of a Complex Biogeography in the Squid-Vibrio Symbiosis. mBio 2020; 11:mBio.00853-20. [PMID: 32457244 PMCID: PMC7251207 DOI: 10.1128/mbio.00853-20] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
The complexity, inaccessibility, and time scales of initial colonization of most animal microbiomes present challenges for the characterization of how the bacterial symbionts influence the form and function of tissues in the minutes to hours following the initial interaction of the partners. Here, we use the naturally occurring binary squid-vibrio association to explore this phenomenon. Imaging of the spatiotemporal landscape of this symbiosis during its onset provides a window into the impact of differences in both host-tissue maturation and symbiont strain phenotypes on the establishment of a dynamically stable symbiotic system. These data provide evidence that the symbionts shape the host-tissue landscape and that tissue maturation impacts the influence of strain-level differences on the daily rhythms of the symbiosis, the competitiveness for colonization, and antibiotic sensitivity. Microbes live in complex microniches within host tissues, but how symbiotic partners communicate to create such niches during development remains largely unexplored. Using confocal microscopy and symbiont genetics, we characterized the shaping of host microenvironments during light organ colonization of the squid Euprymna scolopes by the bacterium Vibrio fischeri. During embryogenesis, three pairs of invaginations form sequentially on the organ’s surface, producing pores that lead to interior compressed tubules at different stages of development. After hatching, these areas expand, allowing V. fischeri cells to enter and migrate ∼120 μm through three anatomically distinct regions before reaching blind-ended crypt spaces. A dynamic gatekeeper, or bottleneck, connects these crypts with the migration path. Once V. fischeri cells have entered the crypts, the bottlenecks narrow, and colonization by the symbiont population becomes spatially restricted. The actual timing of constriction and restriction varies with crypt maturity and with different V. fischeri strains. Subsequently, starting with the first dawn following colonization, the bottleneck controls a lifelong cycle of dawn-triggered expulsions of most of the symbionts into the environment and a subsequent regrowth in the crypts. Unlike other developmental phenotypes, bottleneck constriction is not induced by known microbe-associated molecular patterns (MAMPs) or by V. fischeri-produced bioluminescence, but it does require metabolically active symbionts. Further, while symbionts in the most mature crypts have a higher proportion of live cells and a greater likelihood of expulsion at dawn, they have a lower resistance to antibiotics. The overall dynamics of these distinct microenvironments reflect the complexity of the host-symbiont dialogue.
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Jiao X, Fu MD, Wang YY, Xue J, Zhang Y. Bifidobacterium and Lactobacillus for preventing necrotizing enterocolitis in very-low-birth-weight preterm infants: a systematic review and meta-analysis. World J Pediatr 2020; 16:135-142. [PMID: 31482480 DOI: 10.1007/s12519-019-00297-5] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 07/18/2019] [Indexed: 01/12/2023]
Abstract
BACKGROUND The therapeutic effect of Bifidobacterium and Lactobacillus on necrotizing enterocolitis (NEC) in very-low-birth-weight preterm infants was controversial, and we aimed to explore the exact impact of the two probiotics. METHODS The PubMed, EMBASE, Web of Science and Cochrane Library were systematically searched for studies published from January 1, 2010 to February 28, 2019. Results were combined with fixed-effect model or random-effect model with specific conditions. Sensitivity analysis was conducted by the trim-and-fill method, and the Begger's and Egger's test were used to measure publication bias. RESULTS The meta-analysis included 16 original articles with 4632 very-low-birth-weight preterm infants. With respect to the intervention of Bifidobacterium, we estimated non-significant decrease in the morbidity of NEC with a risk ratio (RR) of 0.75 [95% confidence internal (CI) 0.56-1.01, P = 0.06]. Regarding the effect of Lactobacillus, there was no evidence of significant lower risk in the incidence of NEC (RR = 0.67, 95% CI 0.39-1.17, P = 0.16). The use of mixture of probiotics (Bifidobacterium and Lactobacillus) reduced the risk of NEC in the probiotics group (RR = 0.45, 95% CI 0.25-0.80, P = 0.007). CONCLUSION The mixture of Bifidobacterium and Lactobacillus could prevent the morbidity of NEC in very-low-birth-weight preterm infants. But Bifidobacterium or Lactobacillus alone did not show this effect.
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Affiliation(s)
- Xue Jiao
- School of Medicine, Shandong University, Jinan, China
| | - Meng-Di Fu
- School of Medicine, Shandong University, Jinan, China
| | - Ya-Yun Wang
- Department of Neonatology, Second Hospital of Shandong University, 247# Beiyuan Road, Jinan, China
| | - Jiang Xue
- Department of Neonatology, Second Hospital of Shandong University, 247# Beiyuan Road, Jinan, China
| | - Yuan Zhang
- Center of Evidence-Based Medicine, Institute of Medical Sciences, Second Hospital of Shandong University, 247# Beiyuan Road, Jinan, China. .,School of Public Health, Shandong University, Jinan, China.
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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: 106] [Impact Index Per Article: 21.2] [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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Kappel SS, Sangild PT, Hilsted L, Hartmann B, Thymann T, Aunsholt L. Gastric Residual to Predict Necrotizing Enterocolitis in Preterm Piglets As Models for Infants. JPEN J Parenter Enteral Nutr 2020; 45:87-93. [PMID: 32100882 DOI: 10.1002/jpen.1814] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 01/23/2020] [Accepted: 02/04/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Necrotizing enterocolitis (NEC) is a serious intestinal inflammatory disease in preterm infants. High volume of gastric residual (GR) after oral feedings is often used as a predictor of NEC, but evidence is limited. Using NEC-sensitive preterm piglets as models, we hypothesized that GR mass and related plasma biomarkers predict early onset of NEC. METHODS In total, 258 newborn preterm piglets were fed bovine milk-based formulas for 5 days. At euthanasia, the stomach, small intestine, and colon were evaluated for NEC lesions. Mass, acidity, gastrin, and bile acid levels were determined for GR content, together with gastrin, glucagon-like peptide 2 (GLP-2), and gastric inhibitory polypeptide (GIP) levels in plasma. RESULTS In total, 48% of piglets had NEC lesions in the small intestine and/or colon. These piglets had higher GR mass (+32%, P < 0.001) and lower gastric bile acid concentrations (-22%, P < 0.05) than piglets without NEC lesions. The positive and negative predictive values for these markers were 34%-61%. Gastric acidity, gastrin, GLP-2, and GIP levels were similar for piglets with and without NEC lesions. CONCLUSION Elevated GR mass correlates positively with NEC lesions but may be a poor predictor of NEC, even when combined with other biomarkers. More knowledge about gastric emptying and gut transit in preterm neonates is required to understand how GR volume and composition relate to morbidities, such as NEC, in preterm neonates.
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Affiliation(s)
- Susanne Soendergaard Kappel
- Comparative Pediatrics and Nutrition, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark
| | - Per Torp Sangild
- Comparative Pediatrics and Nutrition, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark
| | - Linda Hilsted
- Department of Clinical Biochemistry, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark
| | - Bolette Hartmann
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.,Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Thomas Thymann
- Comparative Pediatrics and Nutrition, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark
| | - Lise Aunsholt
- Department of Neonatology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark
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Early Biomarkers in Neonatal Necrotizing Enterocolitis: A Pilot Study. JOURNAL OF POPULATION THERAPEUTICS AND CLINICAL PHARMACOLOGY 2019; 26:e1-e8. [PMID: 31904200 DOI: 10.15586/jptcp.v26i3.602] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 08/20/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Necrotizing enterocolitis (NEC) is a frequent serious disease of the digestive system in neonates. It is considered as an important cause of serious neonatal complication and death. Therefore, its early suspicion and proper management are important. AIM Early and sensitive detection of neonatal NEC through determination of levels of fecal calprotectin (FCP), serum levels of procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), epithelial neutrophil activating peptide-78 (ENA-78), and interleukin 18 (IL-18). METHOD This prospective case control study was conducted in Tanta University Hospital from June 2016 to March 2018. The study included 20 healthy neonates (control group) and 20 NEC newborn patients. They were all subjected to the measurement of levels of FCP and serum levels of hs-CRP, PCT, ENA-78, IL-18, Malondialdehyde (MDA), and total antioxidant capacity (TAC). Receiver operating characteristic (ROC) curve analysis was conducted for FCP, ENA-78, PCT, hs-CRP, and IL-18. RESULTS The study found a detectable increase in FCP level and serum levels of hs-CRP, PCT, ENA-78, IL-18, and MDA in NEC group in comparison to their levels in the control group. Also, it found a detectable decline in the levels of TAC in comparison to its level in the control group. CONCLUSION FCP, ENA-78, and PCT can be considered as early markers for diagnosis of NEC.
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Barreiros Mota I, Marques C, Faria A, Neto MT, Cordeiro-Ferreira G, Virella D, Pita A, Pereira-da-Silva L, Calhau C. Colonisation of the proximal intestinal remnant in newborn infants with enterostomy: a longitudinal study protocol. BMJ Open 2019; 9:e028916. [PMID: 31767579 PMCID: PMC6886948 DOI: 10.1136/bmjopen-2019-028916] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 09/17/2019] [Accepted: 10/15/2019] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION The gut microbiota plays a main role in the maintenance of host's health. Exposure to different conditions in early life contributes to distinct 'pioneer' bacterial communities in the intestine, which shape the newborn infant development. Newborn infants with congenital malformations of the gastrointestinal tract (CMGIT), necrotising enterocolitis (NEC) and spontaneous intestinal perforation (SIP) commonly require abdominal surgery and enterostomy. The knowledge about the colonisation of these newborns' intestine by microorganisms is scarce. This protocol is designed to explore the microbial colonisation over time of the proximal intestinal remnant in newborn infants who underwent surgery for CMGIT, NEC or SIP and require enterostomy. METHODS AND ANALYSIS The literature about microbiota colonisation in newborn infants with enterostomy was reviewed and an observational, longitudinal, prospective study was designed. The infants will be recruited at the Neonatal Intensive Care Unit of the Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central. Samples of the enterostomy effluent will be collected every 3 days, through 21 days after the first collection. The microorganisms colonising the proximal intestinal remnant will be identified using the 16S rRNA sequence analysis and a subset of microorganisms will be quantified using real-time PCR. This protocol may serve as basis for future observational and interventional studies on the modulation of the intestinal microbiota (eg, probiotics) on short and long-term outcomes in this population. ETHICS AND DISSEMINATION This study protocol was approved by the Ethics Committee of Centro Hospitalar Universitário de Lisboa Central (441/2017) and by the Ethics Committee of NOVA Medical School, Universidade Nova de Lisboa (n°50/2018/CEFCM). The results will be spread through peer-reviewed publications and presentations at international scientific meetings. TRIAL REGISTRATION NUMBER NCT03340259.
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Affiliation(s)
- Inês Barreiros Mota
- Nutrition and Metabolism, NOVA Medical School | Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
- CINTESIS - Center for Health Technology and Services Research, Porto, Portugal
| | - Cláudia Marques
- Nutrition and Metabolism, NOVA Medical School | Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
- CINTESIS - Center for Health Technology and Services Research, Porto, Portugal
| | - Ana Faria
- Nutrition and Metabolism, NOVA Medical School | Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
- CINTESIS - Center for Health Technology and Services Research, Porto, Portugal
- Comprehensive Health Research Centre, Universidade NOVA de Lisboa, Lisbon, Portugal
| | - Maria Teresa Neto
- Neonatal Intensive Care Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
- Medicine of Woman, Childhood and Adolescence, NOVA Medical School | Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
| | - Gonçalo Cordeiro-Ferreira
- Neonatal Intensive Care Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
| | - Daniel Virella
- Neonatal Intensive Care Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
- Research Unit, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
| | - Ana Pita
- Neonatal Intensive Care Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
| | - Luís Pereira-da-Silva
- Neonatal Intensive Care Unit, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
- Medicine of Woman, Childhood and Adolescence, NOVA Medical School | Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
- Research Unit, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
| | - Conceição Calhau
- Nutrition and Metabolism, NOVA Medical School | Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal
- CINTESIS - Center for Health Technology and Services Research, Porto, Portugal
- Unidade Universitária Lifestyle Medicine, José de Mello Saúde by NOVA Medical School, Lisbon, Portugal
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Hosny M, Baptiste E, Levasseur A, La Scola B. Molecular epidemiology of Clostridium neonatale and its relationship with the occurrence of necrotizing enterocolitis in preterm neonates. New Microbes New Infect 2019; 32:100612. [PMID: 31737279 PMCID: PMC6849425 DOI: 10.1016/j.nmni.2019.100612] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Revised: 10/02/2019] [Accepted: 10/07/2019] [Indexed: 12/15/2022] Open
Abstract
Clostridia-especially Clostridium butyricum-are among the taxa most frequently identified from stool samples of preterm neonates with necrotizing enterocolitis (NEC). Recently, Clostridium neonatale has also been detected from epidemic cases, but using a culture-based approach we were unable to confirm this discovery in a local cohort. In order to investigate this link by a molecular approach, a specific rpoB-based quantitative real-time PCR was developed to detect C. neonatale directly from patients' stool specimens. Design of this rpoB-based quantitative real-time PCR was based on the genomic analysis of seven clinical isolates of C. neonatale. It was tested on stool samples from 88 preterm neonates with necrotizing enterocolitis and 71 matched controls. C. neonatale was significantly more prevalent in stools from preterm neonates with necrotizing enterocolitis than in controls (respectively 30/88 (34%) versus 9/71 (13%); p 0.003). Whole-genome analysis also allowed the identification of three genomic clusters of C. neonatale. This clustering was associated with a geographical location regardless of isolation from the NEC or control, suggesting asymptomatic carriage. Although less prevalent than C. butyricum in our cohort, C. neonatale is significantly associated with the occurrence of necrotizing enterocolitis.
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Affiliation(s)
| | | | | | - B. La Scola
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique, Hôpitaux de Marseille (AP-HM), Microbes, Evolution, Phylogeny and Infection (MEΦI), Institut Hospitalo-Universitaire (IHU), Méditerranée Infection, France
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Li YF, Zhu CR, Gong XL, Li HL, Xiong LK, Wang KJ, Liu GS. Beneficial Effects of Probiotic Treatment on Gut Microbiota in Very Low Birth Weight Infants. Gastroenterol Res Pract 2019; 2019:3682836. [PMID: 31772570 PMCID: PMC6854177 DOI: 10.1155/2019/3682836] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2019] [Revised: 08/12/2019] [Accepted: 09/09/2019] [Indexed: 02/05/2023] Open
Abstract
The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiota. In the present study, a total of 36 VLBW infants were randomly divided into two groups, who were treated with combined probiotics and placebo, and 72 fecal specimens on days 14 and 28 of life were collected from them. Finally, 32 fecal specimens extracted from 16 preterm VLBW infants were qualified and analyzed using 16S rRNA gene sequencing. The primary outcome was to evaluate the change of gut microbiota in VLBW infants after combined probiotic supplement. The secondary outcome was to analyze the correlation gut microbial composition and levels of cytokines. We found that probiotic treatment, but not placebo, decreased the α-diversity of gut microbiota in VLBW infants. At the phylum level, probiotic treatment strongly increased the abundance of Firmicutes, whereas that of Proteobacteria was significantly reduced. At the family level, Streptococcaceae and Lactobacillaceae became prevalent after probiotic treatment, while the relative abundance of Enterobacteriaceae was reduced in the meantime. Most notably, significant correlations were observed between Lactobacillaceae abundance and serum cytokine levels. Further studies are required to shed more light on the characteristics of gut microbiota of VLBW neonates. And the modulation of microbiota should be considered to improve the survival rate of VLBW infants.
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Affiliation(s)
- Yue-feng Li
- Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China
- Department of Pediatrics, Shenzhen Luohu Maternity and Child Health Hospital, 518019, China
| | - Chuan-rui Zhu
- Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China
| | - Xue-lei Gong
- Department of Pediatrics, Shenzhen Luohu Maternity and Child Health Hospital, 518019, China
| | - Hui-ling Li
- Department of Neonatology, Bao'an Maternal and Child Health Hospital, Shenzhen 518133, China
| | - Li-kuan Xiong
- Central Laboratory, Bao'an Maternal and Child Health Hospital, Shenzhen 518133, China
| | - Ke-jian Wang
- Lin He's Academician Workstation of New Medicine and Clinical Translation, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou 510150, China
| | - Guo-Sheng Liu
- Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China
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Hosny M, Abdallah RA, Bou Khalil J, Fontanini A, Baptiste E, Armstrong N, La Scola B. Clostridium pacaense: a new species within the genus Clostridium. New Microbes New Infect 2019; 28:6-10. [PMID: 30740227 PMCID: PMC6357548 DOI: 10.1016/j.nmni.2018.12.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 12/21/2018] [Accepted: 12/21/2018] [Indexed: 11/29/2022] Open
Abstract
Using the strategy of taxonogenomics, we described Clostridium pacaense sp. nov. strain Marseille-P3100T, a Gram-variable, nonmotile, spore-forming anaerobic bacillus. This strain was isolated from a 3.3-month-old Senegalese girl with clinical aspects of marasmus. The closest species based on 16S ribosomal RNA was Clostridium aldenense, with a similarity of 98.4%. The genome length was 2 672 129 bp, with a 50% GC content; 2360 proteins were predicted. Finally, predominant fatty acids were hexadecanoic acid, tetradecanoic acid and 9-hexadecenoic acid.
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Affiliation(s)
- M. Hosny
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique—Hôpitaux de Marseille (AP-HM), Microbes, Evolution, Phylogeny and Infection (MEΦI), Institut Hospitalo-Universitaire (IHU)-Méditerranée Infection, Marseille, France
| | - R. Abou Abdallah
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique—Hôpitaux de Marseille (AP-HM), Vecteurs—Infections Tropicales et Méditerrannéennes (VITROME), Service de Santé des Armées, IHU-Méditerranée Infection, Marseille, France
| | - J. Bou Khalil
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique—Hôpitaux de Marseille (AP-HM), Microbes, Evolution, Phylogeny and Infection (MEΦI), Institut Hospitalo-Universitaire (IHU)-Méditerranée Infection, Marseille, France
| | - A. Fontanini
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique—Hôpitaux de Marseille (AP-HM), Microbes, Evolution, Phylogeny and Infection (MEΦI), Institut Hospitalo-Universitaire (IHU)-Méditerranée Infection, Marseille, France
| | - E. Baptiste
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique—Hôpitaux de Marseille (AP-HM), Microbes, Evolution, Phylogeny and Infection (MEΦI), Institut Hospitalo-Universitaire (IHU)-Méditerranée Infection, Marseille, France
| | - N. Armstrong
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique—Hôpitaux de Marseille (AP-HM), Microbes, Evolution, Phylogeny and Infection (MEΦI), Institut Hospitalo-Universitaire (IHU)-Méditerranée Infection, Marseille, France
| | - B. La Scola
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique—Hôpitaux de Marseille (AP-HM), Microbes, Evolution, Phylogeny and Infection (MEΦI), Institut Hospitalo-Universitaire (IHU)-Méditerranée Infection, Marseille, France
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Hosny M, Bou Khalil JY, Caputo A, Abdallah RA, Levasseur A, Colson P, Cassir N, La Scola B. Multidisciplinary evaluation of Clostridium butyricum clonality isolated from preterm neonates with necrotizing enterocolitis in South France between 2009 and 2017. Sci Rep 2019; 9:2077. [PMID: 30765857 PMCID: PMC6376027 DOI: 10.1038/s41598-019-38773-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Accepted: 12/12/2018] [Indexed: 01/28/2023] Open
Abstract
The association between Clostridium species identification from stool samples in preterm neonates and the occurrence of necrotizing enterocolitis has been increasingly reported. To confirm the specific impact of Clostridium butyricum in this pathology, selective culture procedure was used for Clostridia isolation. Whole-genome analysis was employed to investigate genomic relationships between isolates. Stool samples from present study, as well as from previously investigated cases, were implicated including 88 from preterm neonates with necrotizing enterocolitis and 71 from matched controls. Quantitative real-time polymerase chain reaction was performed to evaluate the presence of C. butyricum from stools of new cases. Clostridium species prevalence isolated by culture was compared between patients with necrotizing enterocolitis and controls. By combining results of both culture and quantitative polymerase chain reaction methods, C. butyricum was significantly more frequent in stool samples from preterm neonates with necrotizing enterocolitis than in controls. Whole-genome analysis of 81 genomes including 58 neonates' isolates revealed that cases were clustered depending on geographical origin of isolation. Controls isolates presented genomic relations with that of patients suggesting a mechanism of asymptomatic carriage. Overall, this suggests an epidemiology comparable to that observed in Clostridium difficile colitis in adults.
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Affiliation(s)
- Michel Hosny
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique - Hôpitaux de Marseille (AP-HM), Microbes, Evolution, Phylogeny and Infection (MEΦI), Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, Marseille, France
| | - Jacques Yaacoub Bou Khalil
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique - Hôpitaux de Marseille (AP-HM), Microbes, Evolution, Phylogeny and Infection (MEΦI), Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, Marseille, France
| | - Aurelia Caputo
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique - Hôpitaux de Marseille (AP-HM), Microbes, Evolution, Phylogeny and Infection (MEΦI), Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, Marseille, France
| | - Rita Abou Abdallah
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique - Hôpitaux de Marseille (AP-HM), Vecteurs - Infections TROpicales et MÉditerrannéennes (VITROME), Service de Santé des Armées, Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, Marseille, France
| | - Anthony Levasseur
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique - Hôpitaux de Marseille (AP-HM), Microbes, Evolution, Phylogeny and Infection (MEΦI), Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, Marseille, France
| | - Philippe Colson
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique - Hôpitaux de Marseille (AP-HM), Microbes, Evolution, Phylogeny and Infection (MEΦI), Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, Marseille, France
| | - Nadim Cassir
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique - Hôpitaux de Marseille (AP-HM), Microbes, Evolution, Phylogeny and Infection (MEΦI), Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, Marseille, France
| | - Bernard La Scola
- Aix-Marseille Université UM63, Institut de Recherche pour le Développement IRD 198, Assistance Publique - Hôpitaux de Marseille (AP-HM), Microbes, Evolution, Phylogeny and Infection (MEΦI), Institut Hospitalo-Universitaire (IHU) - Méditerranée Infection, Marseille, France.
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Abstract
Necrotizing enterocolitis is a devastating intestinal disease affecting preterm infants. In spite of ongoing research and advancement in neonatal care, mortality remains high, especially in infants with advanced disease. The mechanism of disease development, the progression of intestinal injury, and management remain areas of ongoing research and controversy. In this review, we examine our current understanding of the disease, its epidemiology, the risk factors associated with the development of the disease, and its pathophysiology. We also describe current management and new emerging research highlighting potential future directions.
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Affiliation(s)
- Mashriq Alganabi
- Division of General and Thoracic Surgery, Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Carol Lee
- Division of General and Thoracic Surgery, Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Edoardo Bindi
- Division of General and Thoracic Surgery, Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Bo Li
- Division of General and Thoracic Surgery, Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Agostino Pierro
- Division of General and Thoracic Surgery, Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada
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Avelar Rodriguez D, Peña Vélez R, Toro Monjaraz EM, Ramirez Mayans J, Ryan PM. The Gut Microbiota: A Clinically Impactful Factor in Patient Health and Disease. ACTA ACUST UNITED AC 2018. [DOI: 10.1007/s42399-018-0036-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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42
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Olson JK, Navarro JB, Allen JM, McCulloh CJ, Mashburn-Warren L, Wang Y, Varaljay VA, Bailey MT, Goodman SD, Besner GE. An enhanced Lactobacillus reuteri biofilm formulation that increases protection against experimental necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol 2018; 315:G408-G419. [PMID: 29848024 PMCID: PMC6415713 DOI: 10.1152/ajpgi.00078.2018] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 05/09/2018] [Accepted: 05/23/2018] [Indexed: 02/06/2023]
Abstract
One significant drawback of current probiotic therapy for the prevention of necrotizing enterocolitis (NEC) is the need for at least daily administration because of poor probiotic persistence after enteral administration, increasing the risk of the probiotic bacteria causing bacteremia or sepsis if the intestines are already compromised. We previously showed that the effectiveness of Lactobacillus reuteri ( Lr) in preventing NEC is enhanced when Lr is grown as a biofilm on the surface of dextranomer microspheres (DM). Here we sought to test the efficacy of Lr administration by manipulating the Lr biofilm state with the addition of biofilm-promoting substances (sucrose and maltose) to DM or by mutating the Lr gtfW gene (encoding an enzyme central to biofilm production). Using an animal model of NEC, we determined that Lr adhered to sucrose- or maltose-loaded DM significantly reduced histologic injury, improved host survival, decreased intestinal permeability, reduced intestinal inflammation, and altered the gut microbiome compared with Lr adhered to unloaded DM. These effects were abolished when DM or GtfW were absent from the Lr inoculum. This demonstrates that a single dose of Lr in its biofilm state decreases NEC incidence. Importantly, preloading DM with sucrose or maltose further enhances Lr protection against NEC in a GtfW-dependent fashion, demonstrating the tunability of the approach and the potential to use other cargos to enhance future probiotic formulations. NEW & NOTEWORTHY Previous clinical trials of probiotics to prevent necrotizing enterocolitis have had variable results. In these studies, probiotics were delivered in their planktonic, free-living form. We have developed a novel probiotic delivery system in which Lactobacillus reuteri (Lr) is delivered in its biofilm state. In a model of experimental necrotizing enterocolitis, this formulation significantly reduces intestinal inflammation and permeability, improves survival, and preserves the natural gut microflora compared with the administration of Lr in its free-living form.
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Affiliation(s)
- Jacob K Olson
- Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Department of Pediatric Surgery, Nationwide Children's Hospital , Columbus, Ohio
| | - Jason B Navarro
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital , Columbus, Ohio
| | - Jacob M Allen
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital , Columbus, Ohio
| | - Christopher J McCulloh
- Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Department of Pediatric Surgery, Nationwide Children's Hospital , Columbus, Ohio
| | - Lauren Mashburn-Warren
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital , Columbus, Ohio
| | - Yijie Wang
- Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Department of Pediatric Surgery, Nationwide Children's Hospital , Columbus, Ohio
| | - Vanessa A Varaljay
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital , Columbus, Ohio
| | - Michael T Bailey
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital , Columbus, Ohio
| | - Steven D Goodman
- Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital , Columbus, Ohio
| | - Gail E Besner
- Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Department of Pediatric Surgery, Nationwide Children's Hospital , Columbus, Ohio
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43
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Rosa CP, Brancaglion GA, Miyauchi-Tavares TM, Corsetti PP, de Almeida LA. Antibiotic-induced dysbiosis effects on the murine gastrointestinal tract and their systemic repercussions. Life Sci 2018; 207:480-491. [DOI: 10.1016/j.lfs.2018.06.030] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Revised: 06/20/2018] [Accepted: 06/28/2018] [Indexed: 02/07/2023]
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Gan X, Li J. [Research advances in necrotizing enterocolitis in neonates]. ZHONGGUO DANG DAI ER KE ZA ZHI = CHINESE JOURNAL OF CONTEMPORARY PEDIATRICS 2018; 20:164-168. [PMID: 29429468 PMCID: PMC7389245 DOI: 10.7499/j.issn.1008-8830.2018.02.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 11/18/2017] [Accepted: 01/02/2018] [Indexed: 06/08/2023]
Abstract
Necrotizing enterocolitis (NEC) is a catastrophic disease caused by a variety of factors in neonates, especially preterm infants. Severe NEC has a high fatality rate, and most survivors may face short- and long-term adverse prognosis. Risk factors for NEC include preterm birth, non-breastfeeding, microbial abnormalities in the digestive tract, and ischemia-reperfusion injury. High-resolution abdominal ultrasound helps with the early diagnosis of NEC. The preventive measures for NEC include protecting the intestinal mucosa through nutritional intervention, interfering with intestinal injury signals, changing intestinal microflora, and performing early minimal enteral nutrition. This disease progresses rapidly, and there are still no effective measures. Supportive care is mainly used for the treatment of this disease, and patients in severe conditions may need surgical treatment. Celastrol, lipopolysaccharide, and fecal transplantation help with the treatment of NEC, but further studies are needed to confirm their clinical effects.
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Affiliation(s)
- Xin Gan
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.
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45
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The Changes of Colonic Bacterial Composition and Bacterial Metabolism Induced by an Early Food Introduction in a Neonatal Porcine Model. Curr Microbiol 2018; 75:745-751. [PMID: 29368025 DOI: 10.1007/s00284-018-1442-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 01/19/2018] [Indexed: 01/12/2023]
Abstract
The impact of an early food introduction on the microbiota composition and microbial metabolism in colon was investigated using a new-born piglet model. At day 4 after birth, 10 litters of piglets were randomly allocated to a sow-rearing group (SR group) and a milk-replacer supplementing group (MRS group) (n = 5). A commercial milk replacer was given to the suckling piglets in the MRS group from the 4th day to the 28th day. Pyrosequencing of the V3-V4 region of the 16S rRNA genes showed that the milk replacer supplementation significantly decreased the relative abundance of Lactobacillus, Clostridium XI, Blautia, Clostridium sensustricto and Escherichia (p = 0.08) in the colon of the piglets, but significantly increased the relative abundance of Paraprevotella on the 28th day. In addition, the abundance of Rumminococcus, Clostridium XlVa, Succiniclasticum, Clostridium IV tended to increase in the MRS group. The concentrations of acetate, propionate, butyrate, valerate and branch-chain fatty acids (BCFAs) in the colonic digesta increased with the milk replacer supplementary in the MRS group. In addition, the milk replacer supplementary increased the expression level of Toll-like receptor 4 (TLR4), but decreased the expression level of interleukin-6 (IL-6) in the colonic mucosa of the piglets. In conclusion, an early food introduction can influence the gut bacterial composition and metabolism, and may further affect the intestinal health by modifying the gene transcription related to the colonic function. These findings may provide some guidelines for the early nutrition supplementation for infants during the lactation period.
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Itani T, Ayoub Moubareck C, Melki I, Rousseau C, Mangin I, Butel MJ, Karam-Sarkis D. Preterm infants with necrotising enterocolitis demonstrate an unbalanced gut microbiota. Acta Paediatr 2018; 107:40-47. [PMID: 28921627 DOI: 10.1111/apa.14078] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 07/21/2017] [Accepted: 09/13/2017] [Indexed: 02/04/2023]
Abstract
AIM This Lebanese study tested the hypothesis that differences would exist in the gut microbiota of preterm infants with and without necrotising enterocolitis (NEC), as reported in Western countries. METHODS This study compared 11 infants with NEC and 11 controls, all born at 27-35 weeks, in three neonatal intensive care units between January 2013 and March 2015. Faecal samples were collected at key time points, and microbiota was analysed by culture, quantitative PCR (qPCR) and temperature temporal gel electrophoresis (TTGE). RESULTS The cultures revealed that all preterm infants were poorly colonised and harboured no more than seven species. Prior to NEC diagnosis, significant differences were observed by qPCR with a higher colonisation by staphylococci (p = 0.034) and lower colonisations by enterococci (p = 0.039) and lactobacilli (p = 0.048) in the NEC group compared to the healthy controls. Throughout the study, virtually all of the infants were colonised by Enterobacteriaceae at high levels. TTGE analysis revealed no particular clusterisation, showing high interindividual variability. CONCLUSION The NEC infants were poorly colonised with no more than seven species, and the controls had a more diversified and balanced gut microbiota. Understanding NEC aetiology better could lead to more effective prophylactic interventions and a reduced incidence.
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Affiliation(s)
- Tarek Itani
- Microbiology Laboratory; Faculty of Pharmacy; Saint-Joseph University; Beirut Lebanon
| | - Carole Ayoub Moubareck
- Microbiology Laboratory; Faculty of Pharmacy; Saint-Joseph University; Beirut Lebanon
- College of Natural and Health Sciences; Zayed University; Dubai UAE
| | - Imad Melki
- Hôtel Dieu de France Hospital; Beirut Lebanon
| | - Clotilde Rousseau
- Department Risk in pregnancy; Hospital University; Paris Descartes University; Sorbonne Paris Cité; Paris France
- Microbiology; Saint-Louis Hospital; APHP; Paris France
| | - Irène Mangin
- Department Risk in pregnancy; Hospital University; Paris Descartes University; Sorbonne Paris Cité; Paris France
- Laboratoire MIEL; Conservatoire national des arts et métiers; Paris France
| | - Marie-José Butel
- Department Risk in pregnancy; Hospital University; Paris Descartes University; Sorbonne Paris Cité; Paris France
| | - Dolla Karam-Sarkis
- Microbiology Laboratory; Faculty of Pharmacy; Saint-Joseph University; Beirut Lebanon
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Anderson G, Vaillancourt C, Maes M, Reiter RJ. Breastfeeding and the gut-brain axis: is there a role for melatonin? Biomol Concepts 2017; 8:185-195. [DOI: 10.1515/bmc-2017-0009] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2017] [Accepted: 06/05/2017] [Indexed: 12/12/2022] Open
Abstract
AbstractThe benefits of breastfeeding over formula feed are widely appreciated. However, for many mothers breastfeeding is not possible, highlighting the need for a significant improvement in the contents of formula feed. In this article, the overlooked role of melatonin and the melatonergic pathways in breast milk and in the regulation of wider breast milk components are reviewed. There is a growing appreciation that the benefits of breastfeeding are mediated by its effects in the infant gut, with consequences for the development of the gut-brain axis and the immune system. The melatonergic pathways are intimately associated with highly researched processes in the gut, gut microbiome and gut-brain axis. As the melatonergic pathways are dependent on the levels of serotonin availability as a necessary precursor, decreased melatonin is linked to depression and depression-associated disorders. The association of breastfeeding and the gut-brain axis with a host of medical conditions may be mediated by their regulation of processes that modulate depression susceptibility. The biological underpinnings of depression include increased levels of pro-inflammatory cytokines, oxidative stress, kynurenine pathway activity and dysregulation of the hypothalamic-pituitary adrenal axis, all of which can decrease melatonergic pathway activity. The inclusion of the melatonergic pathways in the biological interactions of breast milk and gut development has significant theoretical and treatment implications, as well as being important to the prevention of a host of infant-, child- and adult-onset medical conditions.
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Affiliation(s)
- George Anderson
- CRC Scotland & London, Eccleston Square, London SWIV 1PG, UK
| | - Cathy Vaillancourt
- INRS-Armand-Frappier Institute and Center for Interdisciplinary Research on Well-Being, Health, Society and Environment (CINBIOSE), Laval, QC, Canada
| | - Michael Maes
- Deakin University, Department of Psychiatry, Geelong, Australia
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48
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Updating on gut microbiota and its relationship with the occurrence of necrotizing enterocolitis. ACTA ACUST UNITED AC 2017. [DOI: 10.1016/j.humic.2016.09.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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49
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Chang HY, Chen JH, Chang JH, Lin HC, Lin CY, Peng CC. Multiple strains probiotics appear to be the most effective probiotics in the prevention of necrotizing enterocolitis and mortality: An updated meta-analysis. PLoS One 2017; 12:e0171579. [PMID: 28182644 PMCID: PMC5300201 DOI: 10.1371/journal.pone.0171579] [Citation(s) in RCA: 104] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2016] [Accepted: 01/22/2017] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Some oral probiotics have been shown to prevent necrotizing enterocolitis (NEC) and decrease mortality effectively in preterm very low birth weight (PVLBW) infants. However, it is unclear whether a single probiotic or a mixture of probiotics is most effective for the prevention of NEC. OBJECTIVE A meta-analysis was conducted by reviewing the most up to date literature to investigate whether multiple strains probiotics are more effective than a single strain in reducing NEC and death in PVLBW infants. DATA SOURCES Relevant studies were identified by searches of the MEDLINE, EMBASE, and Cochrane CENTRAL databases, from 2001 to 2016. DATA EXTRACTION AND SYNTHESIS The inclusion criteria were randomized controlled trials of any enteral probiotic supplementation that was initiated within the first 7 days and continued for at least 14 days in preterm infants (≤ 34 weeks' gestation) and/or those of a birth weight ≤1500 g. RESULTS A total of 25 trials (n = 7345 infants) were eligible for inclusion in the meta-analysis using a fixed-effects model. Multiple strains probiotics were associated with a marked reduction in the incidence of NEC, with a pooled OR of 0.36 (95% CI, 0.24-0.53; P < .00001). Single strain probiotic using Lactobacillus species had a borderline effect in reducing NEC (OR of 0.60; 95% CI 0.36-1.0; P = .05), but not mortality. Multiple strains probiotics had a greater effectiveness in reducing mortality and were associated with a pooled OR of 0.58 (95% CI, 0.43-0.79; P = .0006). Trials using single strain of Bifidobacterium species and Saccharomyces boulardii did not reveal any beneficial effects in terms of reducing NEC or mortality. CONCLUSION This updated report found that multiple strains probiotics appear to be the most feasible and effective strategy for the prevention of NEC and reduction of mortality in PVLBW neonates. Further clinical trials should focus on which probiotic combinations are most effective.
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MESH Headings
- Enterocolitis, Necrotizing/epidemiology
- Enterocolitis, Necrotizing/microbiology
- Enterocolitis, Necrotizing/mortality
- Enterocolitis, Necrotizing/prevention & control
- Humans
- Infant, Newborn
- Infant, Premature
- Infant, Premature, Diseases/epidemiology
- Infant, Premature, Diseases/microbiology
- Infant, Premature, Diseases/mortality
- Infant, Premature, Diseases/prevention & control
- Infant, Very Low Birth Weight
- Probiotics/administration & dosage
- Probiotics/classification
- Probiotics/therapeutic use
- Randomized Controlled Trials as Topic
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Affiliation(s)
- Hung-Yang Chang
- Department of Pediatrics, MacKay Children’s Hospital, Taipei, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
- Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan
| | - Jin-Hua Chen
- School of Public Health and Biostatistics Center, Taipei Medical University, Taipei, Taiwan
| | - Jui-Hsing Chang
- Department of Pediatrics, MacKay Children’s Hospital, Taipei, Taiwan
| | - Hung-Chih Lin
- Department of Pediatrics, Children’s Hospital and School of Chinese Medicine, China Medical University, Taichung, Taiwan
- * E-mail:
| | - Chien-Yu Lin
- Department of Pediatrics, Hsinchu MacKay Memorial Hospital, Hsinchu city, Taiwan
| | - Chun-Chih Peng
- Department of Pediatrics, MacKay Children’s Hospital, Taipei, Taiwan
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
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50
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Slattery J, MacFabe DF, Frye RE. The Significance of the Enteric Microbiome on the Development of Childhood Disease: A Review of Prebiotic and Probiotic Therapies in Disorders of Childhood. Clin Med Insights Pediatr 2016; 10:91-107. [PMID: 27774001 PMCID: PMC5063840 DOI: 10.4137/cmped.s38338] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 08/30/2016] [Accepted: 09/05/2016] [Indexed: 02/07/2023] Open
Abstract
Recent studies have highlighted the fact that the enteric microbiome, the trillions of microbes that inhabit the human digestive tract, has a significant effect on health and disease. Methods for manipulating the enteric microbiome, particularly through probiotics and microbial ecosystem transplantation, have undergone some study in clinical trials. We review some of the evidence for microbiome alteration in relation to childhood disease and discuss the clinical trials that have examined the manipulation of the microbiome in an effort to prevent or treat childhood disease with a primary focus on probiotics, prebiotics, and/or synbiotics (ie, probiotics + prebiotics). Studies show that alterations in the microbiome may be a consequence of events occurring during infancy and/or childhood such as prematurity, C-sections, and nosocomial infections. In addition, certain childhood diseases have been associated with microbiome alterations, namely necrotizing enterocolitis, infantile colic, asthma, atopic disease, gastrointestinal disease, diabetes, malnutrition, mood/anxiety disorders, and autism spectrum disorders. Treatment studies suggest that probiotics are potentially protective against the development of some of these diseases. Timing and duration of treatment, the optimal probiotic strain(s), and factors that may alter the composition and function of the microbiome are still in need of further research. Other treatments such as prebiotics, fecal microbial transplantation, and antibiotics have limited evidence. Future translational work, in vitro models, long-term and follow-up studies, and guidelines for the composition and viability of probiotic and microbial therapies need to be developed. Overall, there is promising evidence that manipulating the microbiome with probiotics early in life can help prevent or reduce the severity of some childhood diseases, but further research is needed to elucidate biological mechanisms and determine optimal treatments.
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Affiliation(s)
- John Slattery
- Arkansas Children’s Research Institute, Little Rock, AR, USA
- Division of Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Derrick F. MacFabe
- The Kilee Patchell-Evans Autism Research Group, Departments of Psychology (Neuroscience) and Psychiatry, Division of Developmental Disabilities, University of Western Ontario, London, ON, Canada
| | - Richard E. Frye
- Arkansas Children’s Research Institute, Little Rock, AR, USA
- Division of Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
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