Routine Use of Probiotics in Preterm Infants: Longitudinal Impact on the Microbiome and Metabolome

Abstract

Background: Probiotics are live microbial supplements that colonize the gut and potentially exert health benefit to the host. Objectives: We aimed to determine the impact of a probiotic (Infloran®: Lactobacillus acidophilus-NCIMB701748 and Bifidobacterium bifidum-ATCC15696) on the bacterial and metabolic function of the preterm gut while in the neonatal intensive care unit (NICU) and following discharge. Methods: Stool samples (n = 88) were collected before, during, and after probiotic intake from 7 patients, along with time-matched controls from 3 patients. Samples were also collected following discharge home from the NICU. Samples underwent bacterial profiling analysis by 16S rRNA gene sequencing and quantitative PCR (qPCR), as well as metabolomic profiling using liquid chromatography mass spectrometry. Results: Bacterial profiling showed greater Bifidobacterium (15.1%) and Lactobacillus (4.2%) during supplementation compared to the control group (4.0% and 0%, respectively). While Lactobacillus became reduced after the probiotic had been stopped, Bifidobacterium remained high following discharge, suggestive of successful colonisation. qPCR analysis showed a significant increase (p ≤ 0.01) in B. bifidum in infants who received probiotic treatment compared to controls, but no significant increase was observed for L. acidophilus (p = 0.153). Metabolite profiling showed clustering based on receiving probiotic or matched controls, with distinct metabolites associated with probiotic administration. Conclusions: Probiotic species successfully colonise the preterm gut, reducing the relative abundance of potentially pathogenic bacteria, and effecting gut functioning. Bifidobacterium (but not Lactobacillus) colonised the gut in the long term, suggesting the possibility that therapeutically administered probiotics may continue to exert important functional effects on gut microbial communities in early infancy.

Randomized controlled trial on the impact of early-life intervention with bifidobacteria on the healthy infant fecal microbiota and metabolome

“…It is well accepted that the metabolite profile of the gut lumen is dependent on the structure and function of the resident microbiota (50,51). One recent study evaluated the use of probiotics in preterm infants and their impact on the microbiome and metabolome and concluded that metabolite profiles are different between probiotic and control groups, which strengthens our results on the discrimination of B and F infants over time (52). Although little insight is available for nontargeted metabolomics of healthy B and F infants, Wang et al (53) identified 15-methylhexadecanoic acid, galactitol, and maltose as discriminating metabolites for breastfeeding, and b-alanine, dodecanoic acid, glycolic acid, decanoic acid, and tyramine for formula feeding.…”

Dose-interval study of a dual probiotic in preterm infants

“…Our study contributes to a recent finding on the effects of Infloran in the infant gut, whereby increased levels of bifidobacteria were found during and after probiotic administration, and a reduction in the abundance of Lactobacillus  reported after discharge 17. However, the sample size in our study, 8–10 infants per group, is a major limitation as there are many confounding factors that can affect the growth of bifidobacteria during this initial developmental period in life.…”

Temporal bacterial and metabolic development of the preterm gut reveals specific signatures in health and disease

“…have generally shown reduced incidences of NEC [27, 28] and bifidobacteria are known to play fundamental roles in the development and maintenance of a healthy gut microbiome [29, 30]. Thus, the high abundance of bifidobacteria may contribute to the improved health status by aiding gut maturation and preventing over-expression of potentially damaging pathways, although it is also possible that a higher abundance of bifidobacteria simply acts as a marker for a more healthy gut, rather than being directly causative in preterm infants.…”