Abstract

BackgroundThe gut microbiota of breast-fed and formula-fed infants differ significantly, as do the risks for allergies, gut dysfunction, and upper respiratory tract infections. The connections between breast milk, various formulas, and the profiles of gut bacteria to these childhood illnesses, as well as the mechanisms underlying the effects, are not well understood.MethodsWe investigated distal colon microbiota by 16S RNA amplicon sequencing, morphology by histomorphometry, immune response by cytokine expression, and tryptophan metabolism in a pig model in which piglets were sow-fed, or fed soy or dairy milk-based formula from postnatal day (PND) 2 to 21.ResultsFormula feeding significantly (p < 0.05) altered the colon microbiota relative to the sow feeding. A significant reduction in microbial diversity was noted with formula groups in comparison to sow-fed. Streptococcus, Blautia, Citrobacter, Butrycimonas, Parabacteroides, Lactococcus genera were increased with formula feeding relative to sow feeding. In addition, relative to sow feeding, Anaerotruncus, Akkermansia, Enterococcus, Acinetobacter, Christensenella, and Holdemania were increased in milk-fed piglets, and Biliophila, Ruminococcus, Clostridium were increased in soy-fed piglets. No significant gut morphological changes were noted. However, higher cytokine mRNA expression (BMP4, CCL11, CCL21) was observed in the distal colon of formula groups. Formula feeding reduced enterochromaffin cell number and serotonin, but increased tryptamine levels relative to sow feeding.ConclusionOur data confirm that formula diet alters the colon microbiota and appears to shift tryptophan metabolism from serotonin to tryptamine, which may lead to greater histamine levels and risk of allergies in infants.

Highlights

  • The gut microbiota of breast-fed and formula-fed infants differ significantly, as do the risks for allergies, gut dysfunction, and upper respiratory tract infections

  • Non-metric multidimensional scaling (NMDS) plots of β-diversity revealed no dietary difference at the phylum level; a significant diet effect was observed at the genus level with sow-fed animals discriminated from soy- or milk-fed piglets (Fig. 1a)

  • Relative to sow-fed piglets, Biliophila, Ruminococcus, Clostridium were greater with soy formula feeding while Anaerotruncus, Akkermansia, Enterococcus, Acinetobacter, Christensenella, Holdemania were greater with milk feeding

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Summary

Introduction

The gut microbiota of breast-fed and formula-fed infants differ significantly, as do the risks for allergies, gut dysfunction, and upper respiratory tract infections. The connections between breast milk, various formulas, and the profiles of gut bacteria to these childhood illnesses, as well as the mechanisms underlying the effects, are not well understood. Given the similarity of the infant and piglet intestine [8], the neonatal piglet is arguably the most useful model to explore the interaction between infant diets and gut microbiota to understand the mechanisms underlying health complications in infants. Diet-associated alterations in the composition of the infant gut microbiota are well documented, the functional effect on gastrointestinal tract physiology and immune response remains to be fully elucidated. Several exogenous factors including specific dietary components and microbiota alter serotonin release [10, 11] It is not currently known whether the serotonergic pathway is altered by the microbiota in infants and, may be a potential pathway influencing gut immune system development and function

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