Abstract
BackgroundMajor risk factors for necrotizing enterocolitis (NEC) include premature birth and formula feeding in the context of microbial colonization of the gastrointestinal tract. We previously showed that feeding formula composed of lactose vs. corn syrup solids protects against NEC in preterm pigs; however, the microbial and metabolic effects of these different carbohydrates used in infant formula has not been explored.ObjectiveOur objective was to characterize the effects of lactose- and corn syrup solid-based formulas on the metabolic and microbial profiles of preterm piglets and to determine whether unique metabolomic or microbiome signatures correlate with severity or incidence of NEC.Design/methodsPreterm piglets (103 days gestation) were given total parenteral nutrition (2 days) followed by gradual (5 days) advancement of enteral feeding of formulas matched in nutrient content but containing either lactose (LAC), corn syrup solids (CSS), or 1:1 mix (MIX). Gut contents and mucosal samples were collected and analyzed for microbial profiles by sequencing the V4 region of the 16S rRNA gene. Metabolomic profiles of cecal contents and plasma were analyzed by LC/GC mass spectrometry.ResultsNEC incidence was 14, 50, and 44% in the LAC, MIX, and CSS groups, respectively. The dominant classes of bacteria were Bacilli, Clostridia, and Gammaproteobacteria. The number of observed OTUs was lowest in colon contents of CSS-fed pigs. CSS-based formula was associated with higher Bacilli and lower Clostridium from clusters XIVa and XI in the colon. NEC was associated with decreased Gammaproteobacteria in the stomach and increased Clostridium sensu stricto in the ileum. Plasma from NEC piglets was enriched with metabolites of purine metabolism, aromatic amino acid metabolism, and bile acids. Markers of glycolysis, e.g., lactate, were increased in the cecal contents of CSS-fed pigs and in plasma of pigs which developed NEC.ConclusionsFeeding formula containing lactose is not completely protective against NEC, yet selects for greater microbial richness associated with changes in Bacilli and Clostridium and lower NEC incidence. We conclude that feeding preterm piglets a corn syrup solid vs. lactose-based formula increases the incidence of NEC and produces distinct metabolomic signatures despite modest changes in microbiome profiles.
Highlights
Major risk factors for necrotizing enterocolitis (NEC) include premature birth and formula feeding in the context of microbial colonization of the gastrointestinal tract
NEC was associated with decreased Gammaproteobacteria in the stomach and increased Clostridium sensu stricto in the ileum
Feeding formula containing lactose is not completely protective against NEC, yet selects for greater microbial richness associated with changes in Bacilli and Clostridium and lower NEC incidence
Summary
Major risk factors for necrotizing enterocolitis (NEC) include premature birth and formula feeding in the context of microbial colonization of the gastrointestinal tract. Necrotizing enterocolitis (NEC) persists as a major gastrointestinal disease among preterm infants that is characterized by a severe inflammatory response leading to necrosis of intestinal tissue and major morbidity [1, 2]. Recent evidence suggests that the preterm infant gut is not sterile [3, 4], but clearly the process of birth and especially enteral feeding sets off a cascade of physiological processes that lead to increased numbers and diversity of microbes. In preterm infants, gut microbes trigger an exaggerated proinflammatory response leading to necrosis and injury because of immature intestinal innate immune function
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