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Defects in gut barrier function are implicated in gastrointestinal (GI) disorders like inflammatory bowel disease (IBD), as well as in systemic inflammation. With the increasing incidence of IBD worldwide, more attention should be paid to dietary interventions and therapeutics with the potential to boost the natural defense mechanisms of gut epithelial cells. The current study aimed to investigate the protective effects of Limosilactobacillus reuteri ATCC PTA 4659 in a colitis mouse model and delineate the mechanisms behind it. Wild-type mice were allocated to the control group; or given 3% dextran sulfate sodium (DSS) in drinking water for 7 days to induce colitis; or administered L. reuteri for 7 days as pretreatment; or for 14 days starting 7 days before subjecting to the DSS. Peroral treatment with L. reuteri improved colitis severity clinically and morphologically and reduced the colonic levels of Tumor necrosis factor-α (TNF-α) (Tnf), Interleukin 1-β (Il1β), and nterferon-γ (Ifng), the crucial pro-inflammatory cytokines in colitis onset. It also prevented the CD11b+Ly6G+ neutrophil recruitment and the skewed immune responses in mesenteric lymph nodes (MLNs) of CD11b+CD11c+ dendritic cell (DC) expansion and Foxp3+CD4+ T-cell reduction. Using 16S rRNA gene amplicon sequencing and RT-qPCR, we demonstrated a colitis-driven bacterial translocation to MLNs and gut microbiota dysbiosis that were in part counterbalanced by L. reuteri treatment. Moreover, the expression of barrier-preserving tight junction (TJ) proteins and cytoprotective heat shock protein (HSP) 70 and HSP25 was reduced by colitis but boosted by L. reuteri treatment. A shift in expression pattern was also observed with HSP70 in response to the pretreatment and with HSP25 in response to L. reuteri-DSS. In addition, the changes of HSPs were found to be correlated to bacterial load and epithelial cell proliferation. In conclusion, our results demonstrate that the human-derived L. reuteri strain 4659 confers protection in experimental colitis in young mice, while intestinal HSPs may mediate the probiotic effects by providing a supportive protein–protein network for the epithelium in health and colitis.

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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.