Probiotics and Human Milk Differentially Influence the Gut Microbiome and NEC Incidence in Preterm Pigs

Authors

Valeria Melendez Hebib
Diana H Taft
Barbara Stoll
Jinxin Liu
Lee Call
Gregory Guthrie
Nick Jensen
Amy B Hair
David A Mills
Douglas G Burrin

Publication Date

5-31-2023

Journal

Nutrients

DOI

10.3390/nu15112585

PMID

37299550

PMCID

PMC10255242

PubMedCentral® Posted Date

5-31-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Humans, Bifidobacterium longum subspecies infantis, Enterocolitis, Necrotizing, Gastrointestinal Microbiome, Incidence, Milk, Human, Probiotics, Swine, microbiome, necrotizing enterocolitis, premature infant, human milk, Clostridium sensu stricto 1, Clostridium perfringens, human milk oligosaccharide, Bifidobacterium longum subsp. infantis

Abstract

Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. Major risk factors include prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. infantis (BL. infantis), alone and in combination with a human milk oligosaccharide (HMO)—sialylactose (3′SL)—on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. We studied 50 preterm piglets randomized between 5 treatments: (1) Preterm infant formula, (2) Donor human milk (DHM), (3) Infant formula + 3′SL, (4) Infant formula + BL. infantis, and (5) Infant formula and BL. infantis + 3′SL. NEC incidence and severity were assessed through the evaluation of tissue from all the segments of the GI tract. The gut microbiota composition was assessed both daily and terminally through 16S and whole-genome sequencing (WGS) of rectal stool samples and intestinal contents. Dietary BL. infantis and 3′SL supplementation had no effect, yet DHM significantly reduced the incidence of NEC. The abundance of BL. infantis in the gut contents negatively correlated with disease severity. Clostridium sensu stricto 1 and Clostridium perfringens were significantly more abundant in NEC and positively correlated with disease severity. Our results suggest that pre- and probiotics are not sufficient for protection from NEC in an exclusively formula-based diet. The results highlight the differences in microbial species positively associated with both diet and NEC incidence.