Probiotics, gut microbiota, and diseases associated with the immaturity of the digestive tract in very preterm infants
DOI:
https://doi.org/10.15574/SP.2023.131.22Keywords:
probiotics, gut microbiota, necrotizing enterocolitis, sepsis, preterm infantsAbstract
Interruption of the formation of gut microbiota in preterm infants increases the probability of necrotizing enterocolitis (NEC) and late-onset neonatal sepsis (LOS). The use of probiotics can reduce the corresponding risk.
Purpose - to evaluate the clinical effectiveness of enteral administration of Lactobacillus reuteri DSM 17938 in reducing the incidence of NEC, LOS, and overall mortality in infants with gestational age (GA) ≤32 weeks, as well as the effect of the probiotic on the formation of the gut microbiota.
Materials and methods. 100 newborns with GA ≤32 weeks and birth weight ≤1500 g were enrolled in the open randomized study. 50 infants in the probiotic group until reaching postmenstrual age (PMA) of 36 weeks received Lactobacillus reuteri DSM 17938 at a dose of 108 CFU/day with enteral feeding (EF), and 50 infants in the comparison group received standard treatment. The primary effectiveness criteria were the incidence of NEC, LOS, and overall mortality. As the secondary criteria, the duration of the period to reach the full EF, the number of episodes of feeding intolerance, duration of antibacterial therapy, weight at PMA of 36 weeks, and length of hospital stay were used.
Results. The administration of Lactobacillus reuteri DSM 17938 at a dose of 108 CFU/day neither reduced the incidence of NEC and LOS nor overall mortality. This intervention, however, significantly reduced the length of hospital stay in infants with GA ≥28 weeks (56.0 (46.0-71.0) days vs 65.0 (60.0-87.9) days; р=0.03), and was associated with the earlier achievement of full enteral volume (23.0 (16.0-37.0) days vs 30.0 (18.0-37.0) days; р=0.26) and fewer episodes of feeding intolerance in infants with GA <28 weeks (1.0 (1.0-3.0) vs 3.0 (3.0-4.0); р=0.19). No effect of the probiotic therapy on the gut colonization by Lactobacillus spp. and Bifidobacterium spp. was observed.
Conclusions. Enteral administration of Lactobacillus reuteri DSM 17938 improves tolerance to EF and reduces the period to achieve full EF and the total length of hospital stay in preterm infants. The effect of this probiotic on the incidence of NEC and LOS, as well as the postnatal formation of the gut microbiota, requires further study.
The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of all participating institutions. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
References
Arboleya S, Sánchez B, Milani C et al. (2015). Intestinal Microbiota Development in Preterm Neonates and Effect of Perinatal Antibiotics. The Journal of Pediatrics. 166 (3): 538-544. https://doi.org/10.1016/j.jpeds.2014.09.041; PMid:25444008
Athalye-Jape G, Rao S, Patole S. (2016). Lactobacillus reuteri DSM 17938 as a Probiotic for Preterm Neonates. Journal of Parenteral and Enteral Nutrition. 40 (6): 783-794. https://doi.org/10.1177/0148607115588113; PMid:26059900
Chi C, Li C, Buys N et al. (2021). Effects of Probiotics in Preterm Infants: A Network Meta-analysis. Pediatrics. 147 (1): e20200706. https://doi.org/10.1542/peds.2020-0706; PMid:33323491
Cui X, Shi Y et al. (2019). Effects of Lactobacillus reuteri DSM 17938 in preterm infants : a double-blinded randomized controlled study: 1-7. https://doi.org/10.1186/s13052-019-0716-9; PMid:31706331 PMCid:PMC6842458
Cuna A, Morowitz MJ, Ahmed et al. (2021). Dynamics of the preterm gut microbiome in health and disease. American Journal of Physiology-Gastrointestinal and Liver Physiology. 320 (4): G411-G419. https://doi.org/10.1152/ajpgi.00399.2020; PMid:33439103 PMCid:PMC8238167
Didari T, Solki S, Mozaffari S et al. (2014). A systematic review of the safety of probiotics. Expert Opinion on Drug Safety. 13 (2): 227-239. https://doi.org/10.1517/14740338.2014.872627; PMid:24405164
Dobryk D, Dobryk O, Dobryanskyy D. (2022). The effect of enteral lactoferrin supplementation in prevention of morbidity associated with immature digestive tract in premature infants: prospective cohort study. Georgian Medical News. 323: 94-101. http://www.ncbi.nlm.nih.gov/pubmed/35271478.
Dobryk DS, Dobryanskyy DO. (2022). Fecal calprotectin, lactoferrin and morbidity associated with immature digestive tract in preterm infants. Modern pediatrics. Ukraine. 7 (127): 38-45. https://doi.org/10.15574/SP.2022.127.38
European Medicines Agency (EMA). (2010). Report on the Expert Meeting on Neonatal and Paediatric Sepsis. URL: https://www.ema.europa.eu/en/documents/report/report-expert-meeting-neonatal-paediatric-sepsis_en.pdf.
Ford SL, Lohmann P, Preidis GA et al. (2019). Improved feeding tolerance and growth are linked to increased gut microbial community diversity in very-low-birth-weight infants fed mother's own milk compared with donor breast milk. American Journal of Clinical Nutrition. 109 (4): 1088-1097. https://doi.org/10.1093/ajcn/nqz006; PMid:30982856 PMCid:PMC6462428
Greenberg RG, Kandefer S, Smith PB et al. (2017). Late-onset Sepsis in Extremely Premature Infants. Pediatric Infectious Disease Journal. 36 (8): 774-779. https://doi.org/10.1097/INF.0000000000001570; PMid:28709162 PMCid:PMC5627954
Jain L, Vidyasagar D, Xanthou M et al. (1989). In vivo distribution of human milk leucocytes after ingestion by newborn baboons. Archives of Disease in Childhood. 64; 7: 930-933. https://doi.org/10.1136/adc.64.7_Spec_No.930; PMid:2774634 PMCid:PMC1590089
Kaban RK, Hegar B, Rohsiswatmo et al. (2019). Lactobacillus reuteri DSM 17938 Improves Feeding Intolerance in Preterm Infants. Pediatr Gastroenterol Hepatol Nutr. 22 (6): 545-553. https://doi.org/10.5223/pghn.2019.22.6.545; PMid:31777720 PMCid:PMC6856506
Kliegman RM, Walsh MC. (1987). Neonatal necrotizing enterocolitis: Pathogenesis, classification, and spectrum of illness. Current Problems in Pediatrics. 17 (4): 219-288. https://doi.org/10.1016/0045-9380(87)90031-4; PMid:3556038
Korpela K, Blakstad EW, Moltu SJ et al. (2018). Intestinal microbiota development and gestational age in preterm neonates. Scientific Reports. 8 (1): 1-9. https://doi.org/10.1038/s41598-018-20827-x; PMid:29410448 PMCid:PMC5802739
Mack DR. (2004). D(-)-Lactic Acid Producing Probiotics, D(-)-Lactic Acidosis and Infants. Canadian Journal of Gastroenterology. 18 (11): 671-675. https://doi.org/10.1155/2004/342583; PMid:15565207
Mara MA, Good M, Weitkamp J-H. (2018). Innate and adaptive immunity in necrotizing enterocolitis. Seminars in Fetal and Neonatal Medicine. 23 (6): 394-399. https://doi.org/10.1016/j.siny.2018.08.002; PMid:30146477 PMCid:PMC6269198
Martí M, Spreckels JE, Ranasinghe PD et al. (2021). Effects of Lactobacillus reuteri supplementation on the gut microbiota in extremely preterm infants in a randomized placebo-controlled trial. Cell reports. Medicine. 2(3): 100206. https://doi.org/10.1016/j.xcrm.2021.100206; PMid:33763652 PMCid:PMC7974321
Moore TA, Wilson ME. (2011). Feeding Intolerance. Advances in Neonatal Care. 11 (3): 149-154. https://doi.org/10.1097/ANC.0b013e31821ba28e; PMid:21730906
Nimwegen FA, Van Penders J, Stobberingh EE, Postma DS. (2008). Asthma and lower airway disease Mode and place of delivery , gastrointestinal microbiota , and their influence on asthma and atopy. Journal of Allergy and Clinical Immunology. 128 (5): 948-955.e3. https://doi.org/10.1016/j.jaci.2011.07.027; PMid:21872915
Patel RM, Kandefer S, Walsh MC et al. (2015). Causes and Timing of Death in Extremely Premature Infants from 2000 through 2011. New England Journal of Medicine. 372 (4): 331-340. https://doi.org/10.1056/NEJMoa1403489; PMid:25607427 PMCid:PMC4349362
Persaud R, Azad MB, Konya T et al. (2014). IMMUNOLOGY Impact of perinatal antibiotic exposure on the infant gut microbiota at one year of age. Allergy, Asthma & Clinical Immunology. 10; 1: 2-3. https://doi.org/10.1186/1710-1492-10-S1-A31; PMCid:PMC4126021
Rojas MA, Lozano JM, Rojas MX et al. (2012). Prophylactic Probiotics to Prevent Death and Nosocomial Infection in Preterm Infants. Pediatrics. 130 (5): e1113-e1120. https://doi.org/10.1542/peds.2011-3584; PMid:23071204
Sadeghirad B et al. (2020). Probiotics Reduce Mortality and Morbidity in Preterm. Gastroenterology. 159 (2): 467-480. https://doi.org/10.1053/j.gastro.2020.05.096; PMid:32592699 PMCid:PMC8014956
Shadkam MN, Jalalizadeh F, Nasiriani K. (2015). Effects of Probiotic Lactobacillus Reuteri (DSM 17938) on the Incidence of Necrotizing Enterocolitis in Very Low Birth Weight Premature Infants. Iranian Journal of Neonatology. 6; 4: 15-20.
Sharif S, Meader N, Oddie SJ et al. (2020). Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD005496.pub5; PMid:33058137 PMCid:PMC8094746
Spreckels JE, Wejryd E, Marchini G et al. (2021). Lactobacillus reuteri Colonisation of Extremely Preterm Infants in a Randomised Placebo-Controlled Trial. Microorganisms. 9 (5): 915. https://doi.org/10.3390/microorganisms9050915; PMid:33923278 PMCid:PMC8190634
Van den Akker CHP, van Goudoever JB, Shamir R et al. (2020). Probiotics and Preterm Infants: A Position Paper by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Committee on Nutrition and the European Society for Paediatric Gastroenterology Hepatology and Nutrition Working Group for Pr. Journal of Pediatric Gastroenterology and Nutrition. 70 (5): 664-680. https://doi.org/10.1097/MPG.0000000000002655; PMid:32332478
Wandro S, Osborne S, Enriquez C et al. (2018). The Microbiome and Metabolome of Preterm Infant Stool Are Personalized and Not Driven by Health Outcomes, Including Necrotizing Enterocolitis and Late-Onset Sepsis. MSphere. 3: 3. https://doi.org/10.1128/mSphere.00104-18; PMid:29875143 PMCid:PMC5990886
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Modern pediatrics. Ukraine
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The policy of the Journal “MODERN PEDIATRICS. UKRAINE” is compatible with the vast majority of funders' of open access and self-archiving policies. The journal provides immediate open access route being convinced that everyone – not only scientists - can benefit from research results, and publishes articles exclusively under open access distribution, with a Creative Commons Attribution-Noncommercial 4.0 international license (СС BY-NC).
Authors transfer the copyright to the Journal “MODERN PEDIATRICS. UKRAINE” when the manuscript is accepted for publication. Authors declare that this manuscript has not been published nor is under simultaneous consideration for publication elsewhere. After publication, the articles become freely available on-line to the public.
Readers have the right to use, distribute, and reproduce articles in any medium, provided the articles and the journal are properly cited.
The use of published materials for commercial purposes is strongly prohibited.