Persistence of Suspected Probiotic Organisms in Preterm Infant Gut Microbiota Weeks After Probiotic Supplementation in the NICU

Abstract

Probiotics are becoming a prevalent supplement to prevent necrotizing enterocolitis in infants born preterm. However, little is known about the ability of these live bacterial supplements to colonize the gut or how they affect endogenous bacterial strains and the overall gut community. We capitalized on a natural experiment resulting from a policy change that introduced the use of probiotics to preterm infants in a single Neonatal Intensive Care Unit. We used amplicon sequence variants (ASVs) derived from the v3 region of the 16S rRNA gene to compare the prevalence and abundance of Bifidobacterium and Lactobacillus in the gut of preterm infants who were and were not exposed to a probiotic supplement in-hospital. Infants were followed to 5 months corrected age. In the probiotic-exposed infants, ASVs belonging to species of Bifidobacterium appeared at high relative abundance during probiotic supplementation and persisted for up to 5 months. In regression models that controlled for the confounding effects of age and antibiotic exposure, probiotic-exposed infants had a higher abundance of the suspected probiotic bifidobacteria than unexposed infants. Conversely, the relative abundance of Lactobacillus was similar between preterm groups over time. Lactobacillus abundance was inversely related to antibiotic exposure. Furthermore, the overall gut microbial community of the probiotic-exposed preterm infants at term corrected age clustered more closely to samples collected from 10day old full-term infants than to samples from unexposed preterm infants at term age. In conclusion, routine in-hospital administration of probiotics to preterm infants resulted in the potential for colonization of the gut with probiotic organisms post-discharge and effects on the gut microbiome as a whole. Further research is needed to fully discriminate probiotic bacterial strains from endogenous strains and to explore their functional role in the gut microbiome and in infant health.

To Probiotic or Not to Probiotic: A Metagenomic Comparison of the Discharge Gut Microbiome of Infants Supplemented With Probiotics in NICU and Those Who Are Not

“…However, our results suggest that Bifidobacterium persists beyond this time point, as the genus was present in all 23 infants with samples collected > 36-weeks gestation. This supports previous studies that have observed long-term probiotic-species colonization, at least with Bifidobacterium ( 14 , 83 ). As moderate to late-preterm infants are at a lower risk of acute disorders than those born very-preterm ( 34 , 35 ), long-term benefits provided through probiotic-treatment may be more significant for the moderate to late-preterm demographic.…”

Colonization of Supplemented Bifidobacterium breve M-16V in Low Birth Weight Infants and Its Effects on Their Gut Microbiota Weeks Post-administration

“…These findings suggest that infant-type HRB are more effective colonizers of the infant gut. Consistent with this finding, it was shown the persistent colonization of probiotic strains of B. longum , B. bifidum , and B. breve up to 5 months after supplementation of commercially probiotics containing these Bifidobacterium strains and Lactobacillus rhamnosus strain in preterm infants ( Yousuf et al, 2020 ). Another study also indicated that the administration of B. longum subsp.…”

“…Probiotics supplementation is a promising approach to improve dysbiosis and prevent gut microbiota-associated diseases in LBW infants. However, it is unclear whether the microbial components in probiotic treatments can persist in the gut during early life, although some studies indicated the potential for some probiotics ( Frese et al, 2017 ; Alcon-Giner et al, 2020 ; Yousuf et al, 2020 ) as described below. This study found the colonization of B. breve M-16V in the intestinal tract of most LBW infants for at least several weeks following cessation of its administration as a probiotic.…”

“…lactis BB-12 from soon after birth increased the abundance of Bifidobacterium in the gut microbiota of very preterm infants during supplementation period. Furthermore, potential long-term contribution of probiotic strains on development of gut microbiota in preterm infants have been indicated by some researches ( Alcon-Giner et al, 2020 ; Yousuf et al, 2020 ). On the other hand, a double-blind, randomized placebo-controlled intervention showed that intake of Lactobacillus acidophilus NCFM or B. animalis subsp.…”

The effect of probiotic supplementation on the gut microbiota of preterm infants

“…infantis, B. lactis and S. thermophilus exist between probiotic and control infants. Finally, the detection of the probiotic species in samples collected prior to supplementation could indicate some cross-colonization took place while the infants were in the neonatal unit, which has previously been reported [20,[28][29][30].…”