Abstract
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.
Highlights
Complex interactions between the gut microbiota, the epithelial barrier, and the host immune system determine intestinal homeostasis
We found that the expression of cytoprotective HSPs was reduced by colitis that coincided with changes in TJ protein expression, inflammatory responses, and gut microbiota dysbiosis
We studied the protective effects of L. reuteri ATCC PTA 4659 by employing a chemical model of colitis with 3% dextran sulfate sodium (DSS) administration in young mice
Summary
Complex interactions between the gut microbiota, the epithelial barrier, and the host immune system determine intestinal homeostasis. A breakdown of regulatory pathways in any of these components may lead to chronic inflammatory conditions and inflammatory bowel disease (IBD) [1, 2]. Despite multiple contributors to disease pathogenesis, one common feature of IBD is identified, i.e., the disruption of the intestinal barrier or the so-called leaky gut [3]. Animal models [4–6] and clinical studies [2, 7, 8] have revealed that impaired gut barrier function may be an initial event of IBD, allowing bacteria to approach and leak through the mucosa. It leads to defective microbial clearance and aberrant immunoregulation and provokes an uncontrollable inflammatory signal cascade in the gastrointestinal (GI) tract and the whole body
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