Effect of probiotic supplementation on the gut microbiota in very preterm infants: A systematic review

Objective There is increasing evidence that probiotic supplementation in very preterm infants decreases the risk of necrotising enterocolitis (NEC), sepsis and mortality. The underlying mechanisms, including effects on the gut microbiota, are largely unknown. We aimed to systematically review the available literature on the effects of probiotic supplementation in very preterm infants on gut microbiota development. Design A systematic review in Medline, Embase, Cochrane Library, CINAHL and Web of Science. Setting Neonatal intensive care unit. Patients Premature infants. Intervention Probiotic supplementation. Main outcome measures Gut microbiota. Results A total of 1046 articles were screened, of which 29 were included. There was a large heterogeneity in study design, dose and type of probiotic strains, timepoints of sample collection and analysing techniques. Bifidobacteria and lactobacilli were the most used probiotic strains. The effects of probiotics on alpha diversity were conflicting; however, beta diversity was significantly different between probiotic-supplemented infants and controls in the vast majority of studies. In most studies, probiotic supplementation led to increased relative abundance of the supplemented strains and decreased abundance of genera such as Clostridium, Streptococcus, Klebsiella and Escherichia. Conclusions Probiotic supplementation to preterm infants seems to increase the relative abundance of the supplemented strains with a concurrent decrease of potentially pathogenic species. These probiotic-induced microbial alterations may contribute to the decreased risk of health complications such as NEC. Future trials, including omics technologies to analyse both microbiota composition and function linked to health outcomes, are warranted to identify the optimal mixture and dosing of probiotic strains.