Premature Infant Fecal Metabolite Profiles Are Modulated in a Probiotic Specific Manner

Abstract

Abstract Objectives The acquisition and succession of intestinal microbiota represents a critical factor in early life development. However, infants born prematurely exhibit a delayed assembly of microbial communities. Supplementation of probiotics help to shift the community to a more favorable structure, thereby promoting a functional benefit. We investigated the effect of two different probiotics, Lactobacillus reuteri (L. reuteri) or Bifidobacterium longum subsp. Infantis (B. infantis) on fecal metabolite profiles in premature infants. Methods This study included 43 very low birth weight (< 1500 grams) premature infants. A dose of L. reuteri (1 × 109 CFU) or B. infantis (8 × 1010 CFU) was provided daily as standard of care until 34 weeks corrected gestational age (CGA). Samples of feces and milk were collected at 30 and 32 weeks CGA. Fecal and milk metabolites were assessed by 1H nuclear magnetic resonance spectroscopy at 298K using a NOESY 1H pre-saturation experiment on a Bruker Avance 600 MHz spectrometer (Bruker BioSpin, Germany). Results Fecal metabolite profiles separated by probiotic group revealing distinct compositions at 30 weeks CGA (Adonis R2 = 0.082, p = 0.023) and was maintained at 32 weeks CGA (Adonis R2 = 0.108, p = 0.001). The separation of groups by fecal metabolites was observed despite similar human milk oligosaccharide (HMO) composition from diet at both 30 weeks (Adonis R2 = 0.034, p = 0.378) and 32 weeks CGA (Adonis R2 = 0.016, p = 0.544). Correlations between milk 2’-fucosyllactose and fecal metabolites revealed trends with fecal acetate and pyruvate at 32 weeks (Pearson's, R = 0.41, p = 0.06 and R = 0.4, p = 0.068 respectively) in the B. infantis group only. Conclusions Fecal metabolite profiles in premature infants are affected by probiotic administration despite similar HMO composition in their diet. Infants receiving L. reuteri exhibit an HMO dominant fecal profile, whereas those receiving B. infantis are more closely oriented with HMO fermentation products indicating a saccharolytic gut microbiota. Funding Sources CS would like to acknowledge funding from the Kinsella endowed chair in Food, Nutrition, and Health as well as USDA-NIFA Hatch project 1021411.