Donkey milk consumption exerts anti-inflammatory properties by normalizing antimicrobial peptides levels in Paneth's cells in a model of ileitis in mice

Eur J Nutr. 2018 Feb;57(1):155-166. doi: 10.1007/s00394-016-1304-z. Epub 2016 Aug 31.

Abstract

Purpose: In this study, we showed the beneficial effects of donkey milk (DM) on inflammatory damages, endogenous antimicrobial peptides levels and fecal microbiota profile in a mice model of Crohn's disease. Nowadays, new strategies of microbiome manipulations are on the light involving specific diets to induce and/or to maintain clinical remission. Interest of DM is explained by its high levels of antimicrobial peptides which confer it anti-inflammatory properties.

Methods: C57BL/6 mice were orally administered with or without indomethacin for 5 days and co-treated with vehicle, DM or heated DM during 7 days. Intestinal length and macroscopic damage scores (MDSs) were determined; ileal samples were taken off for microscopic damage (MD), lysozyme immunostaining and mRNA α-defensin assessments. Ileal luminal content and fecal pellets were collected for lysozyme enzymatic activity and lipocalin-2 (LCN-2) evaluations. Fecal microbiota profiles were compared using a real-time quantitative PCR-based analysis.

Results: Administration of indomethacin caused an ileitis in mice characterized by (1) a decrease in body weight and intestinal length, (2) a significant increase in MDS, MD and LCN-2, (3) a reduction in both α-defensin mRNA expression and lysozyme levels in Paneth's cells reflected by a decrease in lysozyme activity in feces, and (4) a global change in relative abundance of targeted microbial communities. DM treatment significantly reduced almost of all these ileitis damages, whereas heated DM has no impact on ileitis.

Conclusions: DM consumption exerts anti-inflammatory properties in mice by restoring the endogenous levels of antimicrobial peptides which contribute in turn to reduce microbiota imbalance.

Keywords: Antimicrobial peptides; Crohn’s disease; Donkey milk; Dysbiosis; Ileitis.

MeSH terms

  • Animals
  • Anti-Infective Agents / analysis*
  • Anti-Inflammatory Agents / administration & dosage*
  • Equidae*
  • Feces / enzymology
  • Feces / microbiology
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / physiology
  • Ileitis / chemically induced
  • Ileitis / metabolism*
  • Ileitis / pathology
  • Indole Alkaloids / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Milk / chemistry*
  • Muramidase / analysis
  • Muramidase / metabolism
  • Paneth Cells / chemistry
  • Peptides / analysis*
  • RNA, Messenger / analysis
  • alpha-Defensins / genetics

Substances

  • Anti-Infective Agents
  • Anti-Inflammatory Agents
  • Indole Alkaloids
  • Peptides
  • RNA, Messenger
  • alpha-Defensins
  • indimicin B
  • Muramidase