The Combination of Bifidobacterium breve and Three Prebiotic Oligosaccharides Modifies Gut Immune and Endocrine Functions in Neonatal Mice

J Nutr. 2019 Feb 1;149(2):344-353. doi: 10.1093/jn/nxy248.

Abstract

Background: Several types of oligosaccharides are used in infant formula to improve the gut microbiota of formula-fed infants. We previously reported that a combination of 3 oligosaccharides (lactulose, raffinose, and galacto-oligosaccharides; LRG) and Bifidobacterium breve effectively increased B. breve numbers, acetate, and the expression of several immune- and gut hormone-related mRNAs in neonatal mice gut.

Objective: We investigated whether changes in neonatal gut microbiota alter gut immune and endocrine development.

Methods: We first compared postnatal day (PD) 14 with PD21 in C57BL/6J male mouse pups to identify the physiologic immune and endocrine changes during development. In a separate study, we administered phosphate-buffered saline (control group; CON), B. breve M-16V (M-16V), or M-16V + LRG to male mouse pups from PD6 to PD13, and analyzed the gut microbiota and immune and endocrine parameters on PD14 to evaluate whether M-16V + LRG accelerates gut immune and endocrine development.

Results: The proportion of regulatory T (Treg) cells in the CD4+ cells of large intestinal lamina propria lymphocytes (LPLs) was significantly increased (63% higher) at PD21 compared with PD14. The serum glucagon-like peptide (GLP)-1 tended to be lower (P = 0.0515) and that of GLP-2 was significantly lower (58% lower) at PD21 than at PD14. M-16V + LRG significantly increased the Treg proportion in large intestinal LPL CD4+ cells (20% and 29% higher compared with CON and M-16V, respectively) at PD14. M-16V + LRG also caused significant changes in expression of large intestinal mRNAs that are consistent with developmental progression, and increased serum concentrations of GLP-1 (207% and 311% higher compared with CON and M-16V, respectively) and GLP-2 (57% and 97% higher compared with CON and M-16V, respectively) at PD14.

Conclusions: Neonatal administration of M-16V + LRG alters the gut microbiota and enhances gut immune and endocrine development in suckling mice.

Keywords: Bifidobacteria; Th17 cell; oligosaccharides; regulatory T cell; short-chain fatty acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Bifidobacterium breve*
  • Intestines / immunology*
  • Intestines / physiology*
  • Lymph Nodes / cytology
  • Lymphocytes / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mucous Membrane / cytology
  • Oligosaccharides / pharmacology*
  • Prebiotics / administration & dosage*
  • Probiotics / administration & dosage
  • Probiotics / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • T-Lymphocytes, Regulatory

Substances

  • Oligosaccharides
  • Prebiotics
  • RNA, Messenger