Gut dysbiosis as a risk factor of neonatal sepsis among preterm infants
Keywords:
gut dysbiosis; neonatal sepsis; preterm infantsAbstract
Background Preterm infants are at high risk of developing sepsis. An imbalance between the normal gut and pathogenic microbiomes, known as dysbiosis, has been proposed as a condition that leads to neonatal sepsis.
Objective To assess for an association between gut dysbiosis and neonatal sepsis.
Methods A prospective cohort study was conducted involving very preterm or very low birth weight infants admitted to the Neonatal Unit, Cipto Mangunkusumo Hospital, Jakarta, from November 2019 to January 2021. The primary outcome was proven and/or clinical neonatal sepsis. The independent variable was gut dysbiosis, defined as a ratio of normal-to-pathogenic gut microbiome <1.0. Gut microbiome analysis was performed using a polymerase chain reaction test from a fecal specimen. Multivariate analysis using multiple logistic regression was conducted with adjustments for potential confounders.
Results Forty-three infants were recruited during the study period, with a median gestational age of 30 (range 25-36) weeks and birth weight of 1,170 (range 630-1855) grams. Among them, 28 (65.1%) infants had dysbiosis and 25 (58.2%) developed sepsis. The incidence of sepsis was higher among infants with dysbiosis (20 infants; 71.4%) than those without dysbiosis (5 infants; 33.3%). Dysbiosis and hemodynamically significant patent ductus arteriosus increased the risk of sepsis, with aOR 6.93 (95%CI 1.04 to 46.14; P=0.045) and aOR 22.7 (95%CI 1.45 to 355.29; P=0.026), respectively, after adjusting for sex, birthweight, maternal and infant morbidities, as well as maternal and infant vitamin D status.
Conclusion Gut dysbiosis is a risk factor for neonatal sepsis. Maintaining the balance of the gut microbiome is essential from the first day of life.
References
2. Shane AL, Sanchez PJ, Stoll BJ. Neonatal sepsis. Lancet. 2017;390:1770-80. DOI: https://doi.org/10.1016/S0140-6736(17)31002-4
3. Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am. 2013;60:367-89. DOI: https://doi.org/10.1016/j.pcl.2012.12.003
4. Basu S. Neonatal sepsis: the gut connection. Eur J Clin Microbiol Infect Dis. 2015;34:215-22. DOI: https://doi.org/10.1007/s10096-014-2232-6
5. Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Reddy DN. Role of the normal gut microbiota. World J Gastroenterol. 2015;21:8787-803. DOI: https://doi.org/10.3748/wjg.v21.i29.8787
6. Huurre A, Kalliomaki M, Rautava S, Rinne M, Salminen S, Isolauri E. Mode of delivery – effects on gut microbiota and humoral immunity. Neonatology. 2008;93:236-40. DOI: https://doi.org/10.1159/000111102
7. Mazzola G, Murphy K, Ross RP, Gioia DD, Biavati B, Corvaglia LT, et al. Early gut microbiota perturbations following intrapartum antibiotic prophylaxis to prevent group B Streptococcal disease. PLoS One. 2016;11:e0157527. DOI: https://doi.org/10.1371/journal.pone.0157527
8. Pannaraj PS, Li F, Cerini C, Bender JM, Yang S, Rollie A, et al. Association between breast milk bacterial communities and establishment and development of the infant gut microbiome. JAMA Pediatr. 2017;171:647-54. DOI: https://doi.org/10.1001/jamapediatrics.2017.0378
9. DeGruttola AK, Low D, Mizoguchi A, Mizoguchi E. Current understanding of dysbiosis in disease in human and animal models. Inflamm Bowel Dis. 2016;22:1137-50. DOI: https://doi.org/10.1097/MIB.0000000000000750
10. Underwood, MA, Mukhopadhyay S, Lakshminrusimha S, Bevins CL. Neonatal intestinal dysbiosis. J Perinatol. 2020;40:1597–1608. DOI: https://doi.org/10.1038/s41372-020-00829-2
11. Groer MW, Miller EM, D'Agata A, Ho TTB, Dutra SV, Yoo JY, et al. Contributors to dysbiosis in very-low-birth-weight infants. J Obstet Gynecol Neonatal Nurs. 2020;49:232-42. DOI: https://doi.org/10.1016/j.jogn.2020.02.003
12. Madan JC, Salari RC, Saxena D, Davidson L, O’Toole GA, Moore JH, et al. Gut microbial colonization in premature neonates predicts neonatal sepsis. Arch Dis Child Fetal Neonatal Ed. 2012;97:F456-62. DOI: https://doi.org/10.1136/fetalneonatal-2011-301373
13. Mai V, Torrazza RM, Ukhanova M, Wang X, Sun Y, Li N, et al. Distortions in development of intestinal microbiota associated with late onset sepsis in preterm infants. PLoS One. 2013;8:e52876. DOI: https://doi.org/10.1371/journal.pone.0052876
14. Taft DH, Ambalavanan N, Schibler KR, Yu Z, Newburg DS, Deshmukh H, et al. Center variation in intestinal microbiota prior to late-onset sepsis in preterm infants. PLoS One. 2015;10:e0130604. DOI: https://doi.org/10.1371/journal.pone.0130604
15. Alverdy JC, Krezalek MA. Collapse of the microbiome emergence of the pathobiome, and the immunopathology of sepsis. Crit Care Med. 2017;45:337-47. DOI: https://doi.org/10.1097/ccm.0000000000002172
16. Lee CC, Feng Y, Yeh YM, Lien R, Chen CL, Zhou YL, et al. Gut dysbiosis, bacterial colonization and translocation, and neonatal sepsis in very-low-birth-weight preterm infants. Front Microbiol. 2021;12:746111. DOI: https://doi.org/10.3389/fmicb.2021.746111
17. Marsubrin PMT, Firmansyah A, Rohsiswatmo R, Purwosunu Y, Munasir Z, Yuniati T. Vitamin D and T regulator cells are not independent factors for RDS in premature neonates. Pediatr Indones. 2021;61:192-7. DOI: https://doi.org/10.14238/pi61.4.2021.192-7
18. Satar M, Ar?soy AE, Çelik ?H. Turkish Neonatal Society guideline on neonatal infections-diagnosis and treatment. Turk Pediatri Ars. 2018;53(Suppl 1):S88-S100. DOI: https://doi.org/10.5152/TurkPediatriArs.2018.01809
19. Fleischmann C, Reichert F, Cassini A, Horner R, Harder T, Markwart R, et al. Global incidence and mortality of neonatal sepsis: a systematic review and meta-analysis. Arch Dis Child. 2021;106:745–52. DOI: https://doi.org/10.1136/archdischild-2020-320217
20. Wang C, Cui ML, Wang SN, Zhu XP. Intestinal microbiome and its relationship with necrotizing enterocolitis in very low birth weight preterm infants. Zhonghua Er Ke Za Zhi Chin J Pediatr. 2022;60:101–7. DOI: https://doi.org/10.3760/cma.j.cn112140-20211104-00928
21. Verma J, Sankar MJ, Atmakuri K, Agarwal R, Das B. Gut microbiome dysbiosis in neonatal sepsis. Prog Mol Biol Transl Sci. 2022;192:125-47. DOI: https://doi.org/10.1016/bs.pmbts.2022.07.010
22. Milton R, Gillespie D, Dyer C, Taiyari K, Carvalho MJ, Thomson K, et al. Neonatal sepsis and associated factors among newborns in Woldia and Dessie Comprehensive Specialized Hospitals, North?East Ethiopia, 2021. Lancet Glob Health. 2022;10:e661–72. DOI: http://dx.doi.org/10.21203/rs.3.rs-3309937/v1
23. Birrie E, Sisay E, Tibebu NS, Tefera BD, Zeleke M, Tefera Z. Neonatal sepsis and associated factors among newborns in Woldia and Dessie Comprehensive Specialized Hospitals, North?East Ethiopia, 2021. Infect Drug Resist. 2022;15:4169-79. DOI: https://doi.org/10.2147/IDR.S374835
24. Barnette BW, Schumacher BT, Armenta RF, Wynn JL, Richardson A, Bradley JS, Lazar S, Lawrence SM. Contribution of concurrent comorbidities to sepsis-related mortality in preterm infants ?32 weeks of gestation at an academic neonatal intensive care network. Am J Perinatol. 2021;10.1055/a-1675-2899. DOI: https://doi.org/10.1055/a-1675-2899
Downloads
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
Accepted 2025-03-10
Published 2025-04-25
