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), which 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 the 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 two-way ANOVA or Kruskal-Wallis test. Results The DON group exhibited lower final body weight (−12%), jejunal villi height (−41%), jejunal occludin expression (−36%), and higher plasma interleukin (IL)-1β level (+85%) and jejunal Il1b mRNA expression (+98%) than the Veh group (P < 0.05). In contrast, final body weight (+19%), jejunal villi height (+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 p38 and ERK1/2 (−40% and − 38%) were lower in LF + DON compared with DON (P < 0.05). Furthermore, relative abundance of Clostridium XIVa (+181%) and colonic butyrate levels (+53%) were greater in LF + DON compared with DON (P < 0.05). Conclusion Our study highlights a promising antimycotoxin approach of LF to alleviate DON-induced intestinal dysfunction via modulating the mitogen-activated protein kinase (MAPK) pathway and gut microbial community in mice.

Lactoferrin Relieves Deoxynivalenol-Induced Oxidative Stress and Inflammatory Response by Modulating the Nrf2/MAPK Pathways in the Liver

“…Previous research revealed that DON induced a hepatic inflammatory response by promoting the production of pro-inflammatory cytokines, such as IL-1β and TNF-α . Congruently, our previous study showed that DON increased the plasma IL-1β level, and the present findings further support this by revealing that DON upregulated the hepatic mRNA levels of IL1β , IL8 , and TNFα in mice. As expected, LF treatment inhibited the expression of IL1β and TNFα in the liver of DON-exposed mice.…”

“…The groups were as follows: the vehicle group (Veh group) received peroral physiological saline daily with a commercial diet; the LF group received peroral 10 mg of LF/day with a commercial diet; the DON group received peroral physiological saline daily with a DON diet (commercial diet containing 12 mg of DON/kg); and the LF + DON group received peroral 10 mg of LF/day with a DON diet. More detailed information regarding the grouping can be found in previous literature . The composition of the diet is shown in Table S1 of the Supporting Information.…”

“…More detailed information regarding the grouping can be found in previous literature. 23 The composition of the diet is shown in Table S1 of the Supporting Information. The diets were contaminated with fungal culture material that produced DON using the method described previously.…”

Lactoferrin, Osteopontin and Lactoferrin–Osteopontin Complex: A Critical Look on Their Role in Perinatal Period and Cardiometabolic Disorders

“…In fact, LF concomitantly stimulated intestinal epithelium growth and up-regulated the expression of jejunal tight-junction proteins such as zonula occludens and claudins in response to caloric restriction-mediated malnutrition [ 45 ]. The restoration of intestinal integrity, reflected by raised occludin mass and tight junction structure normalization, was caused by the inactivation of the MAPK pathway, in particular via the decrease of p38 and ERK1/2 phosphorylation [ 27 ]. The strengthening of the intestinal barrier was also accompanied by elevated alkaline phosphatase activity and transepithelial electrical resistance, the latter as an indicator of the strength of tight-junction proteins [ 46 ].…”

“…(The images used were extracted from Servier Medical Art). Related references cited in the Figure: ( a : [ 11 , 12 , 13 , 14 , 15 , 16 ]; b : [ 16 , 17 ]; c : [ 18 ]; d : [ 11 , 19 ]; e : [ 19 ]; f : [ 20 , 21 ]; g : [ 20 , 22 ]; h : [ 23 ]; i : [ 24 , 25 , 26 ]; j : [ 25 , 27 , 28 , 29 ]; k : [ 30 , 31 ]; l : [ 32 ]; m : [ 33 , 34 ]; n : [ 11 , 19 ]; o : [ 15 ]; p : [ 11 , 15 , 19 ]; q : [ 16 , 35 , 36 ]; r : [ 16 , 37 ]; s : [ 11 , 35 , 38 ]; t : [ 16 , 38 ]; u : [ 16 ]; v : [ 39 ]; ...…”