Enteric Pathogens and Their Toxin-Induced Disruption of the Intestinal Barrier through Alteration of Tight Junctions in Chickens

Abstract

Maintaining a healthy gut environment is a prerequisite for sustainable animal production. The gut plays a key role in the digestion and absorption of nutrients and constitutes an initial organ exposed to external factors influencing bird’s health. The intestinal epithelial barrier serves as the first line of defense between the host and the luminal environment. It consists of a continuous monolayer of intestinal epithelial cells connected by intercellular junctional complexes which shrink the space between adjacent cells. Consequently, free passing of solutes and water via the paracellular pathway is prevented. Tight junctions (TJs) are multi-protein complexes which are crucial for the integrity and function of the epithelial barrier as they not only link cells but also form channels allowing permeation between cells, resulting in epithelial surfaces of different tightness. Tight junction’s molecular composition, ultrastructure, and function are regulated differently with regard to physiological and pathological stimuli. Both in vivo and in vitro studies suggest that reduced tight junction integrity greatly results in a condition commonly known as “leaky gut”. A loss of barrier integrity allows the translocation of luminal antigens (microbes, toxins) via the mucosa to access the whole body which are normally excluded and subsequently destroys the gut mucosal homeostasis, coinciding with an increased susceptibility to systemic infection, chronic inflammation and malabsorption. There is considerable evidence that the intestinal barrier dysfunction is an important factor contributing to the pathogenicity of some enteric bacteria. It has been shown that some enteric pathogens can induce permeability defects in gut epithelia by altering tight junction proteins, mediated by their toxins. Resolving the strategies that microorganisms use to hijack the functions of tight junctions is important for our understanding of microbial pathogenesis, because some pathogens can utilize tight junction proteins as receptors for attachment and subsequent internalization, while others modify or destroy the tight junction proteins by different pathways and thereby provide a gateway to the underlying tissue. This review aims to deliver an overview of the tight junction structures and function, and its role in enteric bacterial pathogenesis with a special focus on chickens. A main conclusion will be that the molecular mechanisms used by enteric pathogens to disrupt epithelial barrier function in chickens needs a much better understanding, explicitly highlighted for Campylobacter jejuni, Salmonella enterica and Clostridium perfringens. This is a requirement in order to assist in discovering new strategies to avoid damages of the intestinal barrier or to minimize consequences from infections.

Bacillus subtilis B21 and Bacillus licheniformis B26 improve intestinal health and performance of broiler chickens with Clostridium perfringens‐induced necrotic enteritis

“…Tight junctions are multi‐protein complexes which play a crucial role in the physiological functions of epithelial cells, Awad, Hess, and Hess (). Reduced TJ integrity greatly increases ion conductance across the paracellular route resulting in a leaky gut, Tomita and Hayashi ().…”

Montmorillonite improved the intestinal mucosal barrier functions of laying hens in late production

“…The claudin family and occludin are the chief components in the regulation of intestinal epithelial barrier function (Suzuki, ). Claudin 1 and claudin 5 have been characterized in chickens, and both claudins are known to interact and play an important role in ensuring the gut barrier functions (Awad, Hess, & Hess, ). Addition of MMT at increasing levels to the diet increased linearly the mRNA expression of claudin‐1 and claudin‐5 in the jejunum.…”

The bile salt sodium taurocholate inducesCampylobacter jejuniouter membrane vesicle production and increases OMV-associated proteolytic activity

“…Similar studies in E. coli and Salmonella enterica serovar Typhimurium also showed a pathogenic mechanism associated with occludin-specific redistribution (Bertelsen et al, 2004;McNamara et al, 2001;Sakakibara, Furuse, Saitou, Ando-Akatsuka, & Tsukita, 1997). It appears that a number of virulence-associated serine proteases secreted by different enteric pathogens preferentially alter the expression and distribution of occludin, indicating that occludin might be an important IEC target that shapes the bacterial-host interplay (Awad, Hess, & Hess, 2017;Eichner, Protze, Piontek, Krause, & Piontek, 2017;Guttman & Finlay, 2008). Future studies should focus on understanding the precise mechanisms of OMV-associated serine proteases that enteric pathogens including C. jejuni use to interact with and cleave/modify occludin.…”