Effects of Probiotics on Preterm Infant Gut Microbiota Across Populations: A Systematic Review and Meta-Analysis

Microbiota in early life is closely associated with the health of infants, especially premature ones. Probiotics are important drivers of gut microbiota development in preterm infants; however, there is no consensus regarding the characteristics of specific microbiota in preterm infants receiving probiotics. In this study, we performed a meta-analysis of 5 microbiome data sets (1816 stool samples from 706 preterm infants) to compare the gut microbiota of preterm infants exposed to probiotics with that of preterm infants not exposed to probiotics across populations. Despite study-specific variations, we found consistent differences in gut microbial composition and predicted functional pathways between the control and probiotic groups across different cohorts of preterm infants. The enrichment of Acinetobacter, Bifidobacterium, and Lactobacillus spp and the depletion of the potentially pathogenic bacteria Finegoldia, Veillonella, and Klebsiella spp. were the most consistent changes in the gut microbiota of preterm infants supplemented with probiotics. Probiotics drove microbiome transition into multiple preterm gut community types, and notably, preterm gut community type 3 had the highest alpha-diversity, with enrichment of Bifidobacterium and Bacteroides spp. At the functional level, the major predicted microbial pathways involved in peptidoglycan biosynthesis consistently increased in preterm infants supplemented with probiotics; in contrast, the crucial pathways associated with heme biosynthesis consistently decreased. Interestingly, Bifidobacterium sp. rather than Lactobacillus sp. gradually became dominant in gut microbiota of preterm infants using mixed probiotics, although both probiotic strains were administered at the same dosage. Taken together, our metaanalysis suggests that probiotics contribute to reshaping the microbial ecosystem of preterm infants at both the taxonomic and functional levels of the bacterial community. More standardized and relevant studies may contribute to better understanding the crosstalk among probiotics, the gut microbiota, and subsequent disease risk, which could help to give timely nutritional feeding guidance to preterm infants. This systematic review and meta-analysis was registered at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/) as CRD42023447901.