Effectiveness of Saccharomyces boulardii combined with phototherapy in the treatment of hyperbilirubinemia in neonates: a prospective randomized controlled trial
TANG Wei1,2, LU Hong-Yan1, SUN Qin1, XU Wei-Min1
Department of Pediatrics, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212000, China
Abstract:Objective To study the effectiveness of Saccharomyces boulardii combined with phototherapy in the treatment of hyperbilirubinemia in neonates. Methods The neonates with hyperbilirubinemia who were hospitalized from January to December 2018 were enrolled and randomly divided into an observation group (n=61) and a control group (n=63). The neonates in the observation group were treated with phototherapy combined with Saccharomyces boulardii, and those in the control group were treated with phototherapy combined with placebo. Treatment outcomes were compared between the two groups. Fecal samples were collected 72 hours after treatment and 16s rRNA high-throughput sequencing was used to compare the features of gut microbiota between the two groups. Results There was no significant difference in the total serum bilirubin level between the two groups before treatment (P > 0.05). At 24, 48, and 72 hours after treatment, the observation group had a significantly lower level of total serum bilirubin than the control group (P < 0.05). Compared with the control group, the observation group had a significantly lower proportion of neonates requiring phototherapy again[20% (12/61) vs 75% (47/63), P < 0.05]. Compared with the control group, the observation group had a significantly higher abundance of Bacteroides (P < 0.05) and a significantly lower abundance of Escherichia coli and Staphylococcus in the intestine at 72 hours after treatment (P < 0.05). Conclusions In neonates with hyperbilirubinemia, phototherapy combined with Saccharomyces boulardii can effectively reduce bilirubin level and prevent the recurrence of jaundice. Saccharomyces boulardii can favour the treatment outcome by regulating the gut microbiota of neonates.
TANG Wei,LU Hong-Yan,SUN Qin et al. Effectiveness of Saccharomyces boulardii combined with phototherapy in the treatment of hyperbilirubinemia in neonates: a prospective randomized controlled trial[J]. CJCP, 2020, 22(11): 1149-1153.
Bhutani VK, Vilms RJ, Hamerman-Johnson L. Universal bilirubin screening for severe neonatal hyperbilirubinemia[J]. J Perinatol, 2010, 30(Suppl 1):S6-S15.
[2]
Najati N, Gharebaghi MM, Mortazavi F. Underlying etiologies of prolonged icterus in neonates[J]. Pak J Biol Sci, 2010, 13(14):711-714.
[3]
Henny-Harry C, Trotman H. Epidemiology of neonatal jaundice at the University Hospital of the West Indies[J]. West Indian Med J, 2012, 61(1):37-42.
[4]
Dollberg S, Atherton HD, Hoath SB. Effect of different phototherapy lights on incubator characteristics and dynamics under three modes of servocontrol[J]. Am J Perinatol, 1995, 12(1):55-60.
[5]
Maayan-Metzger A, Yosipovitch G, Hadad E, et al. Transepidermal water loss and skin hydration in preterm infants during phototherapy[J]. Am J Perinatol, 2001, 18(7):393-396.
[6]
Kopelman AE, Brown RS, Odell GB. The "bronze" baby syndrome:a complication of phototherapy[J]. J Pediatr, 1972, 81(3):466-472.
[7]
Rubaltelli FF, Jori G, Reddi E. Bronze baby syndrome:a new porphyrin-related disorder[J]. Pediatr Res, 1983, 17(5):327-330.
[8]
Aspberg S, Dahlquist G, Kahan T, et al. Is neonatal phototherapy associated with an increased risk for hospitalized childhood bronchial asthma?[J]. Pediatr Allergy Immunol, 2007, 18(4):313-319.
[9]
Martin CR, Cloherty JP. Neonatal hyperbilirubinemia[M]//Cloherty JP, Eichenwald EC, Stark AR. Manual of Neonatal Care. 6th ed. Philadelphia PA:Lippincott Williams and Wilkins, 2008:201.
[10]
Singh M. Jaundice:Care of the Newborn[M]. 7th ed. New Delhi:Sagar Publication, 2010:254-274.
[11]
Demirel G, Celik IH, Erdeve O, et al. Impact of probiotics on the course of indirect hyperbilirubinemia and phototherapy duration in very low birth weight infants[J]. J Matern Fetal Neonatal Med, 2013, 26(2):215-218.
Liu W, Liu H, Wang T, et al. Therapeutic effects of probiotics on neonatal jaundice[J]. Pak J Med Sci, 2015, 31(5):1172-1175.
[14]
Serce O, Gursoy T, Ovali F, et al. Effects of Saccharomyces boulardii on neonatal hyperbilirubinemia:a randomized controlled trial[J]. Am J Perinatol, 2015, 30(2):137-142.
[15]
Jiménez E, Marín ML, Martín R, et al. Is meconium from healthy newborns actually sterile?[J]. Res Microbiol, 2008, 159(3):187-193.
[16]
Palmer C, Bik EM, DiGiulio DB, et al. Development of the human infant intestinal microbiota[J]. PLoS Biol, 2007, 5(7):e177.
[17]
Leser TD, Amenuvor JZ, Jensen TK, et al. Culture-independent analysis of gut bacteria:the pig gastrointestinal tract microbiota revisited[J]. Appl Environ Microbiol, 2002, 68(2):673-690.
[18]
Dave M, Higgins PD, Middha S, et al. The human gut microbiome:current knowledge, challenges, and future directions[J]. Transl Res, 2012, 160:246-257.
Foster TJ, Geoghegan JA, Ganesh VK, et al. Adhesion, invasion and evasion:the many functions of the surface proteins of Staphylococcus aureus[J]. Nat Rev Microbiol, 2014, 12(1):49-62.
[21]
Winstel V, Missiakas D, Schneewind O. Staphylococcus aureus targets the purine salvage pathway to kill phagocytes[J]. Proc Natl Acad Sci U S A, 2018, 115(26):6846-6851.
[22]
Creech CB, Frenck RW, Sheldon EA, et al. Safety, tolerability and immunogenicity of a single dose 4-antigen or 3-antigen Staphylococcus aureus vaccine in healthy older adults[J]. Open Forum Infect Di, 2015, 2(Suppl 1):746.
[23]
Lee E, Kim BJ, Kang MJ, et al. Dynamics of gut microbiota according to the delivery mode in healthy Korean infants[J]. Allergy Asthma Immunol Res, 2016, 8(5):471-477.
[24]
Rocha ER, Smith CJ. Ferritin-like family proteins in the anaerobe Bacteroides fragilis:when an oxygen storm is coming, take your iron to the shelter[J]. Biometals, 2013, 26(4):577-591.
[25]
Wexler AG, Goodman AL. An insider's perspective:Bacteroides as a window into the microbiome[J]. Nat Microbiol, 2017, 2:17026.
[26]
Wallace BD, Roberts AB, Pollet RM, et al. Structure and inhibition of microbiome β-glucuronidases essential to the alleviation of cancer drug toxicity[J]. Chem Biol, 2015, 22(9):1238-1249.
[27]
Pollet RM, D'agostino EH, Walton WG, et al. An Atlas of β-glucuronidases in the human intestinal microbiome[J]. Structure, 2017, 25(7):967-977.e1-e5.
[28]
Madan A, MacMahon JR, Stevenson DK. Neonatal hyperbilirubinemia[M]//Taeusch HV, Ballard RA, Gleason CA. Avery's Diseases of the Newborn. 8th ed. Philadelphia, PA:Elsevier Publication, 2005:1226-1256.