Glycerol monolaurate ameliorates DSS-induced acute colitis by inhibiting infiltration of Th17, neutrophils, macrophages and altering the gut microbiota

Abstract

Background and aimsInflammatory bowel disease (IBD) places a heavy medical burden on countries and families due to repeated and prolonged attacks, and the incidence and prevalence of IBD are increasing worldwide. Therefore, finding an effective treatment is a matter of great urgency. Glycerol monolaurate (GML), which has a twelve-carbon chain, is a compound naturally found in human breast milk. Some studies have shown that GML has antibacterial and anti-inflammatory effects. However, the specific mechanism of action remains unclear.MethodsAcute colitis was established in mice using 3% DSS, and glycerol monolaurate (500 mg·kg−1) was administered for two weeks. QPCR and western blotting were performed to examine the inflammatory status. Mice described were subjected to flow cytometry analysis for immune cell activation.ResultsGML treated alleviated macroscopic symptoms such as shortened colons, increased spleen weight, and caused weight loss in mice with DSS-induced colitis. In addition, GML decreased the expression of pro-inflammatory factors (NF-α, IL-1β and IL-1α) and increased the expression of anti-inflammatory factors (IL-10 and TGF-β). GML inhibited the activation of the MAPK and NF-κB signalling pathways, improved tissue damage, and increased the expression of intestinal tight junction proteins. In addition, LPMCs extracted from intestinal tissue via flow cytometry showed that GML treatment led to a decrease of Th17 cells, Neutrophils and Macrophages. 16S rDNA sequencing showed that GML increased the abundance of commensal bacterium such as Akkermansia and Lactobacillus murinus.ConclusionsWe showed that oral administration of GML ameliorated DSS-induced colitis by inhibiting infiltration of Th17 cells, Neutrophils, and Macrophages, protecting the intestinal mucosal barrier and altered the abundance of commensal bacterium. This study provides new insights into the biological function and therapeutic potential of GML in the treatment of IBD.

Effects of dietary supplementation of glycerol monolaurate on laying performance, egg quality, antioxidant capacity, intestinal morphology and immune function in late-phase laying hens

“…Moreover, GML showed immunomodulatory activities as evidenced by inhibited T cell receptor ( TCR )-induced the production of the cytokines IL-2, IFN-γ, TNF-α, and IL-10 ( Zhang, 2018 ). Glycerol monolaurate alleviates dextran sodium sulphate ( DSS )-induced colitis by increasing the expression of anti-inflammatory cytokines (IL-10, TGF-β), and decreasing the expression of proinflammatory cytokines (TNF-α, IL-1β, IL-1α) ( He et al, 2022 ). Mo et al (2019) demonstrated that GML modulated the composition of gut microbiota and short chain fatty acid concentrations in a dose-dependent manner to improve intestinal health in mice.…”

Glycerol monolaurate regulates apoptosis and inflammation by suppressing lipopolysaccharide-induced ROS production and NF-κB activation in avian macrophages

“…Glycerol monolaurate has also been shown to inhibit B cell receptor-induced cytokine production, phosphorylation of signaling proteins, and protein clustering ( Fosdick et al, 2022 ). Moreover, oral administration of GML inhibits the infiltration of macrophages and reduces the expression of proinflammatory factors, thereby contributing to the alleviation of experimental colitis in mice ( He et al, 2022 ). However, the modulatory effects of GML on avian macrophages are not yet known.…”

Discovery of a Bromodomain and Extra Terminal Domain (BET) Inhibitor with the Selectivity for the Second Bromodomain (BD2) and the Capacity for the Treatment of Inflammatory Diseases

“… − Th17 cells secrete cytokines interleukin-17 (IL-17), which stimulates the secretion and expression of several inflammatory factors and chemokines, such as IL-6, TNF-α, IL-1β, and IL-22, by activating the NF-κB and MAPK pathways. This leads to the recruitment and activation of multiple immune cells, causing or worsening tissue inflammation. − Targeting Th17 cells has become a promising approach to treat inflammatory diseases. − The production of Th17 cells from CD4 + T cells is tightly regulated by chromatin gene transcription, a complex process involving the collective activity of critical transcription factors. Among them, the bromodomain and extra terminal domain (BET) proteins play significant roles in the complex process. − The classical Pan-BET inhibitor JQ-1 has been shown to effectively suppress the Th17 cell differentiation …”