Rules of Engagement: Epithelial-Microbe Interactions and Inflammatory Bowel Disease

Abstract

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex, multifactorial disorders that lead to chronic and relapsing intestinal inflammation. The exact etiology remains unknown, however multiple factors including the environment, genetic, dietary, mucosal immunity, and altered microbiome structure and function play important roles in disease onset and progression. Supporting this notion that the gut microbiota plays a pivotal role in IBD pathogenesis, studies in gnotobiotic mice have shown that mouse models of intestinal inflammation require a microbial community to develop colitis. Additionally, antimicrobial therapy in some IBD patients will temporarily induce remission further demonstrating an association between gut microbes and intestinal inflammation. Finally, a dysfunctional intestinal epithelial barrier is also recognized as a key pathogenic factor in IBD. The intestinal epithelium serves as a barrier between the luminal environment and the mucosal immune system and guards against harmful molecules and microorganisms while being permeable to essential nutrients and solutes. Beneficial (i.e., mutualists) bacteria promote mucosal health by strengthening barrier integrity, increasing local defenses (mucin and IgA production) and inhibiting pro-inflammatory immune responses and apoptosis to promote mucosal homeostasis. In contrast, pathogenic bacteria and pathobionts suppress expression and localization of tight junction proteins, cause dysregulation of apoptosis/proliferation and increase pro-inflammatory signaling that directly damages the intestinal mucosa. This review article will focus on the role of intestinal epithelial cells (IECs) and the luminal environment acting as mediators of barrier function in IBD. We will also share some of our translational observations of interactions between IECs, immune cells, and environmental factors contributing to maintenance of mucosal homeostasis, as it relates to GI inflammation and IBD in different animal models.

Canine chronic enteropathy—Current state-of-the-art and emerging concepts

“…Under appropriate culture conditions, enteroids/colonoids produce all cell types normally found within the intestinal epithelium. Dogs represent a unique large animal model that naturally develops CIE, sharing remarkable similarities in etiology, clinical course, histologic lesions, and interventional strategies to human IBD ( 231 ). The advantages of the dog in relation to other common animal models of intestinal inflammation include their large body size, longer life span, spontaneous (natural) development of CIE, and they possess a GI tract of comparable size, structure, and function to that of humans.…”

Manipulation of the diet–microbiota–brain axis in Alzheimer’s disease

“…A layer of epithelial cells and mucus protects the intestinal barrier, facilitating the translocation of microbes, bacterial products, and other metabolites into the systemic circulation and lymphatic tissue (Zheng et al, 2020). Prominent bacterial molecules, such as SCFAs and LPS are major influencers of this semipermeable barrier by either promoting or inhibiting the translocation of proinflammatory cytokines, affecting the body's immune response (Jergens et al, 2021).…”

Evaluation of Anti-Inflammatory and Antioxidant Effectsof Chrysanthemum Stem and Leaf Extract on Zebrafish Inflammatory Bowel Disease Model

“…Some studies show that about 6.8 million people worldwide suffer from IBD [ 7 ]. In recent years, the pathogenesis of IBD has made some progress, involving environmental factors, psychological factors, genetic factors and intestinal microbes [ 8 , 9 ], but the specific pathogenesis is not clear. The main manifestations of the patient are abdominal pain, diarrhea, fever, weight loss, and possible sub-occlusion (spasm pain, vomiting, difficulty with feces/discharge) or other complications (i.e., abscess, fistula) [ 10 ].…”