Probiotics, gut microbiota, and diseases associated with the immaturity of the digestive tract in very preterm infants

Abstract

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.