Lactoferrin Attenuates Intestinal Barrier Dysfunction and Inflammation by Modulating the MAPK Pathway and Gut Microbes in Mice

J Nutr. 2022 Nov;152(11):2451-2460. doi: 10.1093/jn/nxac200. Epub 2022 Sep 2.

Abstract

Background: Deoxynivalenol (DON) is a major mycotoxin present in staple foods (particularly in cereal products) that induces intestinal inflammation and disrupts intestinal integrity. Lactoferrin (LF) is a multifunctional protein that contributes to maintaining intestinal homeostasis and improving host health. However, the protective effects of LF on DON-induced intestinal dysfunction remain unclear.

Objectives: This study aimed to investigate the effects of LF on DON-induced intestinal dysfunction in mice, and its underlying protective mechanism.

Methods: Male BALB/c mice (5 wk old) with similar body weights were divided into 4 groups (n = 6/group) and treated as follows for 5 wk: Veh [peroral vehicle daily, commercial (C) diet]; LF (peroral 10 mg LF/d, C diet); DON (Veh, C diet containing 12 mg DON/kg); and LF + DON (peroral 10 mg LF/d, DON diet). Intestinal morphology, tight junction proteins, cytokines, and microbial community were determined. Data were analyzed by 2-factor ANOVA or Kruskal-Wallis test.

Results: The DON group exhibited lower final body weight (-12%), jejunal villus height (VH; -41%), and jejunal occludin expression (-36%), and higher plasma IL-1β concentration (+85%) and jejunal Il1b mRNA expression (+98%) compared with the Veh group (P < 0.05). In contrast, final body weight (+19%), jejunal VH (+49%), jejunal occludin (+53%), and intelectin 1 protein expression (+159%) were greater in LF + DON compared with DON (P < 0.05). Additionally, jejunal Il1b mRNA expression (-31%) and phosphorylation of p38 and extracellular signal regulated kinase 1/2 (-40% and - 38%) were lower in LF + DON compared with DON (P < 0.05). Furthermore, the relative abundance of Clostridium XIVa (+181%) and colonic butyrate concentration (+53%) were greater in LF + DON compared with DON (P < 0.05).

Conclusions: Our study highlights a promising antimycotoxin approach using LF to alleviate DON-induced intestinal dysfunction by modulating the mitogen-activated protein kinase pathway and gut microbial community in mice.

Keywords: MAPK pathway; deoxynivalenol; gut microbial community; intestinal dysfunction; lactoferrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gastrointestinal Microbiome*
  • Inflammation / chemically induced
  • Intestinal Diseases*
  • Lactoferrin / pharmacology
  • MAP Kinase Signaling System*
  • Male
  • Mice
  • Occludin / genetics
  • RNA, Messenger
  • Trichothecenes* / toxicity

Substances

  • Lactoferrin
  • Occludin
  • RNA, Messenger
  • Trichothecenes
  • deoxynivalenol