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

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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.

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Abbreviations

CD:

Crohn’s disease

DAPI:

4’6-diamidino-2-phenylindole

DM:

Donkey milk

GULDA:

GUt low-density array

IBD:

Inflammatory bowel disease

MD:

Microscopic damage

MDS:

Macroscopic damage scores

NSAIDs:

Non-steroidal anti-inflammatory drugs

PBS:

Phosphate-buffered saline

PCA:

Principal component analysis

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Acknowledgments

The authors acknowledge “Les Ânes d’Autan” and “La ferme du Hitton” for providing donkey milk. This work was supported by Ecole d’Ingénieurs de PURPAN (Toulouse, France) and Institut National Ânes et Mulets (Paris, France).

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Authors and Affiliations

  1. UMR 1331 Toxalim INRA, INP-ENVT, INP-PURPAN, Université de Toulouse 3 Paul Sabatier, Neuro-Gastroenterology and Nutrition Group, 180 chemin de Tournefeuille–BP.93173, 31027, Toulouse Cedex 3, France

    Sophie Yvon, Maïwenn Olier, Mathilde Leveque & Hélène Eutamène

  2. Département des Sciences Agronomiques et Agroalimentaire, équipe Agroalimentaire et Nutrition, Université de Toulouse INP-PURPAN, 75 voie du TOEC, 31076, Toulouse Cedex 3, France

    Sophie Yvon, Gwenaëlle Jard, Helene Tormo, Djamila Ali Haimoud-Lekhal, Magali Peter & Hélène Eutamène

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  1. Sophie Yvon
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Sophie Yvon, Maïwenn Olier, Mathilde Leveque, Gwenaëlle Jard, Helene Tormo, Djamila Ali Haimoud-Lekhal, Magali Peter, Hélène Eutamène have no conflict of interest.

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Yvon, S., Olier, M., Leveque, M. et al. 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 57, 155–166 (2018). https://doi.org/10.1007/s00394-016-1304-z

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