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

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. J Nutr 2022;152:2451–2460