Role of Bifidobacterium in Modulating the Intestinal Epithelial Tight Junction Barrier: Current Knowledge and Perspectives.

The intestinal tight junction (TJ) barrier is a crucial defense mechanism that prevents the passage of intestinal content into the intestinal wall, tissue, and systemic circulation. A compromised intestinal TJ barrier has been identified as a significant factor in inflammatory bowel disease (IBD), necrotizing enterocolitis, and other gut-related inflammatory conditions. Recent studies have revealed the importance of the probiotic bacterial strains of Bifidobacterium in protecting against intestinal inflammation and IBD pathogenesis via the regulation of intestinal TJ barrier function. Numerous species and strains of Bifidobacterium have been found to regulate TJ proteins and the signaling pathways responsible for maintaining intestinal barrier integrity and permeability. In this review, we provide a summary of recent studies that highlight the regulatory role of Bifidobacterium species and the strain effect on the intestinal TJ barrier. We also discuss the intracellular mechanisms involved in Bifidobacterium modulation of the intestinal barrier and the potential therapeutic efficacy of targeting the barrier function to regulate intestinal inflammation.

Behavioural differences underlie toxicity and predation variation in blooms of Prymnesium parvum.

Much of the evolutionary ecology of toxic algal blooms (TABs) remains unclear, including the role of algal toxins in the adaptive 'strategies' of TAB-forming species. Most eukaryotic TABs are caused by mixotrophs that augment autotrophy with organic nutrient sources, including competing algae (intraguild predation). We leverage the standing diversity of TABs formed by the toxic, invasive mixotroph Prymnesium parvum to identify cell-level behaviours involved in toxin-assisted predation using direct observations as well as comparisons between genetically distinct low- and high-toxicity isolates. Our results suggest that P. parvum toxins are primarily delivered at close range and promote subsequent prey capture/consumption. Surprisingly, we find opposite chemotactic preferences for organic (prey-derived) and inorganic nutrients between differentially toxic isolates, respectively, suggesting behavioural integration of toxicity and phagotrophy. Variation in toxicity may, therefore, reflect broader phenotypic integration of key traits that ultimately contribute to the remarkable flexibility, diversity, and success of invasive populations.

Matrix Metalloproteinase-9 (MMP-9) induced disruption of intestinal epithelial tight junction barrier is mediated by NF-κB activation.

BACKGROUND: Matrix Metalloproteinase-9 (MMP-9) has been shown to play a key role in mediating inflammation and tissue damage in inflammatory bowel disease (IBD). In patients with IBD, the intestinal tight junction (TJ) barrier is compromised as characterized by an increase in intestinal permeability. MMP-9 is elevated in intestinal tissue, serum and stool of patients with IBD. Previous studies from our laboratory showed that MMP-9 causes an increase in intestinal epithelial TJ permeability and that the MMP-9 induced increase in intestinal permeability is an important pathogenic factor contributing to the development of intestinal inflammation in IBD. However, the intracellular mechanisms that mediate the MMP-9 modulation of intestinal barrier function remain unclear. AIMS: The main aim of this study was to further elucidate the molecular mechanisms involved in MMP-9 induced increase in intestinal epithelial TJ permeability using Caco-2 monolayers as an in-vitro model system. RESULTS: MMP-9 induced increase in Caco-2 TJ permeability was associated with activation and cytoplasmic-to-nuclear translocation of NF-κB p65. Knocking-down NF-κB p65 by siRNA transfection prevented the MMP-9 induced expression of the NF-κB target gene IL-8, myosin light chain kinase (MLCK) protein expression, and subsequently prevented the increase in Caco-2 TJ permeability. In addition, the effect of MMP-9 on Caco-2 intestinal epithelial TJ barrier function was not mediated by apoptosis or necrosis. CONCLUSION: Our data show that the MMP-9 induced disruption of Caco-2 intestinal epithelial TJ barrier function is regulated by NF-κB pathway activation of MLCK.

Talk about micromanaging! Role of microRNAs in intestinal barrier function.

Defective intestinal tight-junction (TJ) barrier has been implicated in the pathogenesis of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), and other inflammatory conditions of the gut. The role of microRNAs (miRNA's or miR's) has also been demonstrated in the last two decades in the pathogenesis of IBD and in the regulation of intestinal TJ barrier function. MiRNAs are noncoding regulators of gene expression at the posttranscription level that have an essential role in targeting transcripts encoding proteins of intestinal TJs and their regulators. Many miRNAs have been reported to regulate or deregulate the TJ proteins responsible for the intestinal barrier integrity and intestinal permeability. Many of those miRNAs have been reported to have essential roles in the pathogenesis of IBD. In this mini-review, we summarize the results of studies in the last three years that implicate miRNAs in the defective TJ barrier in relation to IBD. The therapeutic potential of using specific miRNAs to target the intestinal TJ barrier might be of great insight for IBD therapy.