Colonisation of the proximal intestinal remnant in newborn infants with enterostomy: a longitudinal study protocol

Inês Barreiros Mota, Cláudia Marques, Ana Faria, Maria Teresa Neto, Gonçalo Cordeiro-Ferreira, Daniel Virella, Ana Pita, Luís Pereira-da-Silva, Conceição Calhau, Inês Barreiros Mota, Cláudia Marques, Ana Faria, Maria Teresa Neto, Gonçalo Cordeiro-Ferreira, Daniel Virella, Ana Pita, Luís Pereira-da-Silva, Conceição Calhau

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.

Keywords: congenital malformations of the gastrointestinal tract; dysbiosis; enterostomy; microbiota; necrotizing enterocolitis; newborn infants.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Schedule of effluent sampling during study period.

References

    1. Koh A, De Vadder F, Kovatcheva-Datchary P, et al. . From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 2016;165:1332–45. 10.1016/j.cell.2016.05.041
    1. Stecher B. The roles of inflammation, nutrient availability and the commensal microbiota in enteric pathogen infection. Microbiol Spectr 2015;3 10.1128/microbiolspec.MBP-0008-2014
    1. van den Elsen LWJ, Poyntz HC, Weyrich LS, et al. . Embracing the gut microbiota: the new frontier for inflammatory and infectious diseases. Clin Trans Immunol 2017;6:e125 10.1038/cti.2016.91
    1. DiBartolomeo ME, Claud EC. The developing microbiome of the preterm infant. Clin Ther 2016;38:733–9. 10.1016/j.clinthera.2016.02.003
    1. Hill CJ, Lynch DB, Murphy K, et al. . Evolution of gut microbiota composition from birth to 24 weeks in the INFANTMET cohort. Microbiome 2017;5 10.1186/s40168-016-0213-y
    1. Arrieta M-C, Stiemsma LT, Amenyogbe N, et al. . The intestinal microbiome in early life: health and disease. Front Immunol 2014;5:427 10.3389/fimmu.2014.00427
    1. Berrington JE, Stewart CJ, Embleton ND, et al. . Gut microbiota in preterm infants: assessment and relevance to health and disease. Arch Dis Child Fetal Neonatal Ed 2013;98:F286–90. 10.1136/archdischild-2012-302134
    1. Collado MC, Cernada M, Neu J, et al. . Factors influencing gastrointestinal tract and microbiota immune interaction in preterm infants. Pediatr Res 2015;77:726–31. 10.1038/pr.2015.54
    1. Cong X, Xu W, Janton S, et al. . Gut microbiome developmental patterns in early life of preterm infants: impacts of feeding and gender. PLoS One 2016;11:e0152751–19. 10.1371/journal.pone.0152751
    1. Hartz LE, Bradshaw W, Brandon DH, et al. . Potential NICU Environmental Influences on the Neonate’s Microbiome: A Systematic Review. Adv Neonatal Care 2015;15:324–35.
    1. Cilieborg MS, Boye M, Sangild PT. Bacterial colonization and gut development in preterm neonates. Early Hum Dev 2012;88:S41–9. 10.1016/j.earlhumdev.2011.12.027
    1. Sachin C. Amin, MDA, Cleo Pappas, MLISb, Hari Iyengar, MDC, and Akhil Maheshwari MD. Short Bowel Syndrome in the Nicu 2014;40:1–19.
    1. Younge N, Yang Q, Seed PC. Enteral high Fat-Polyunsaturated fatty acid blend alters the pathogen composition of the intestinal microbiome in premature infants with an enterostomy. J Pediatr 2017;181:93–101. 10.1016/j.jpeds.2016.10.053
    1. Kanamori Y, Iwanaka T, Sugiyama M, et al. . Early use of probiotics is important therapy in infants with severe congenital anomaly. Pediatr Int 2010;52:362–7. 10.1111/j.1442-200X.2009.02963.x
    1. Romano-Keeler J, Moore DJ, Wang C, et al. . Early life establishment of site-specific microbial communities in the gut. Gut Microbes 2014;5:192–201. 10.4161/gmic.28442
    1. Barrett E, Guinane CM, Ryan CA, et al. . Microbiota diversity and stability of the preterm neonatal ileum and colon of two infants. Microbiologyopen 2013;2:215–25. 10.1002/mbo3.64
    1. Wall R, Hussey SG, Ryan CA, et al. . Presence of two Lactobacillus and Bifidobacterium probiotic strains in the neonatal ileum. Isme J 2008;2:83–91. 10.1038/ismej.2007.69
    1. Marques C, Meireles M, Norberto S, et al. . High-Fat diet-induced obesity rat model: a comparison between Wistar and Sprague-Dawley rat. Adipocyte 2015;5:1–11.
    1. Zoetendal EG, Heilig HGHJ, Klaassens ES, et al. . Isolation of DNA from bacterial samples of the human gastrointestinal tract. Nat Protoc 2006;1:870–3. 10.1038/nprot.2006.142
    1. Marques C, Fernandes I, Meireles M, et al. . Gut microbiota modulation accounts for the neuroprotective properties of anthocyanins. Sci Rep 2018;8:1–9. 10.1038/s41598-018-29744-5
    1. Wang I-K, Lai H-C, Yu C-J, et al. . Real-Time PCR analysis of the intestinal microbiotas in peritoneal dialysis patients. Appl Environ Microbiol 2012;78:1107–12. 10.1128/AEM.05605-11
    1. Gosiewski T, Salamon D, Szopa M, et al. . Quantitative evaluation of fungi of the genus Candida in the feces of adult patients with type 1 and 2 diabetes - a pilot study. Gut Pathog 2014;6:43 10.1186/s13099-014-0043-z
    1. Linetzky Waitzberg D, Alves Pereira CC, Logullo L, et al. . Microbiota benefits after inulin and partially hydrolized guar gum supplementation: a randomized clinical trial in constipated women. Nutr Hosp 2012;27:123–9.
    1. Pereira EM, Schuenck RP, Malvar KL, et al. . Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus: methicillin-resistant isolates are detected directly in blood cultures by multiplex PCR. Microbiol Res 2010;165:243–9. 10.1016/j.micres.2009.03.003
    1. Milani C, Duranti S, Bottacini F, et al. . The first microbial colonizers of the human gut: composition, activities, and health implications of the infant gut microbiota. Microbiol Mol Biol Rev 2017;81:1–67. 10.1128/MMBR.00036-17
    1. Hourigan SK, Ta A, Wong WSW, et al. . The microbiome in necrotizing enterocolitis: a case report in twins and minireview. Clin Ther 2016;38:747–53. 10.1016/j.clinthera.2016.02.014
    1. Underwood MA, Sohn K. The microbiota of the extremely preterm infant. Clin Perinatol 2017;44:407–27. 10.1016/j.clp.2017.01.005
    1. Cassir N, Simeoni U, La Scola B. Gut microbiota and the pathogenesis of necrotizing enterocolitis in preterm neonates. Future Microbiol 2016;11:273–92. 10.2217/fmb.15.136
    1. Guyton K, Alverdy JC. The gut microbiota and gastrointestinal surgery. Nat Rev Gastroenterol Hepatol 2017;14:43–54. 10.1038/nrgastro.2016.139
    1. Moles L, Gómez M, Jiménez E, et al. . Preterm infant gut colonization in the neonatal ICU and complete restoration 2 years later. Clin Microbiol Infect 2015;21:936.e1–10. 10.1016/j.cmi.2015.06.003
    1. Patel AL, Mutlu EA, Sun Y, et al. . Longitudinal survey of microbiota in hospitalized preterm very-low-birth-weight infants. J Pediatr Gastroenterol Nutr 2016;62:292–303. 10.1097/MPG.0000000000000913
    1. Unger S, Stintzi A, Shah P, et al. . Gut microbiota of the very-low-birth-weight infant. Pediatr Res 2015;77:205–13. 10.1038/pr.2014.162
    1. Hosny M, Cassir N, La Scola B. Updating on gut microbiota and its relationship with the occurrence of necrotizing enterocolitis. Hum Microbiome J 2017;4:14–19. 10.1016/j.humic.2016.09.002
    1. Vongbhavit K, Underwood MA. Intestinal perforation in the premature infant. J Neonatal Perinatal Med 2017;10:281–9. 10.3233/NPM-16148
    1. Brower-Sinning R, Zhong D, Good M, et al. . Mucosa-Associated bacterial diversity in necrotizing enterocolitis. PLoS One 2014;9:e105046 10.1371/journal.pone.0105046

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa