Preliminary Comparison of Lactobacillus reuteri and Bifidobacterium longum Subspecies Infantis Probiotics Impact on Preterm Infant Gut Microbiome and Length Growth

Abstract

Abstract Objectives The gut microbiome is associated with term infant growth. Here, we examine if use of a L. reuteri or a B. infantis probiotic in preterm infants is associated with changes in the gut microbiome and growth. Methods In this observational study, 26 preterm infants received L. reuteri and 13 infants received B. infantis. Infant length delta z-score was calculated by subtracting the birth length z-score (Fenton Growth Chart) from the discharge z-score value. Association between length delta z-score and probiotic was tested with a t-test. Gut microbiome was assessed by V4 sequencing using the first fecal sample collected in week 2 or 3 of life from each infant. Data analysis was done in QIIME2 and R. Alpha diversity (Shannon index) was compared by probiotic and length delta z-score using regression. Beta diversity (Bray-Curtis distance) was compared between probiotics and above/below median length delta z-score by PERMANOVA. Songbird was used for differential abundance testing. Results There was no association between length and the probiotic infants received, P = 0.34. There was no association between alpha diversity and probiotic, P = 0.58, or length, P = 0.43. There was an association between beta diversity and probiotic (P = 0.001), but not between beta diversity and length, P = 0.43. Songbird top and bottom ranked amplicon sequence variants (ASVs) are those most likely to be differentially abundant. For probiotic, top ranked ASVs (associated with L. reuteri) were Lactobacillus and L. reuteri. Bottom ranked ASVs (B. infantis) were Bifidobacterium and an Escherichia-Shigella. For length, top ranked ASVs (higher delta z-score) were Staphylococcus and probiotic associated Lactobacillus and L. reuteri. Bottom ranked ASVs (lower delta z-score) were Enterococcus, probiotic associated Escherchia-Shigella, Enterobacteriaceae, and Clostridium perfinigens. Conclusions Type of probiotic given was not associated with infant length growth, however, songbird identified ASVs that are likely to be differentially abundant by both probiotic and length. Additional work is needed to confirm the songbird results, and investigation into differences in probiotic administration methods and timing are on-going. Funding Sources F32HD093185 (DHT) and Peter J. Shields Endowed Chair in Dairy Food Science (DAM).