Fig. 2

Role of gut dysbiosis in the development of gut barrier disruption, endotoxemia and hepatic and hypothalamic inflammation under heat stress. A large body of evidence exists that gut dysbiosis, a term used to describe a perturbation of commensal gut bacteria community, develops in broilers and pigs kept at high ambient temperature exceeding the thermoneutral zone. At thermoneutral zone, commensal bacteria promote gut barrier integrity through inhibiting the colonization by pathogens, continuously stimulating intestinal epithelial cells (IEC) to secrete protective mucins (MUC1, MUC2) and antimicrobial peptides (AMP) and contributing to adaptive immunity by stimulating secretion of secretory immunoglobulin A (sIgA). In contrast, at high ambient temperature gut dysbiosis is occurring which leads to an overgrowth of opportunistic pathogens, thereby, leading to a weakening of all decisive structural, biochemical, and immunological elements of the gut barrier, which is visible by a decreased expression and relocalization of tight junction (TJ) proteins, loss of goblet cells, reduced production of mucins, thinning of mucin layer, IEC shedding and IEC villus shortening and hyperpermeability of the gut barrier. As a consequence, intact bacteria and bacterial components, such as lipopolysaccharide (LPS), translocate into the portal vein and cause hepatic inflammation via Toll-like receptor 4 (TLR4)-dependent activation of nuclear factor-kappa B (NF-κB). Activation of NF-κB stimulates production of pro-inflammatory cytokines, such as interleukin (IL1β), IL6 and tumor necrosis factor α (TNFα), which together with LPS enter the systemic circulation, thereby, causing endotoxemia and systemic inflammation. While elevated levels of proinflammatory cytokines and LPS stimulate muscle proteolysis and inhibit muscle protein synthesis, thereby, decreasing lean carcass growth, these cytokines and LPS cause TLR4-dependent hypothalamic inflammation. Hypothalamic inflammation causes activation of neuronal populations that produce anorexigenic neuropeptides, while inhibiting hypothalamic neurons expressing orexigenic neuropeptides, thereby, causing anorexia and decreasing feed intake, which are typical characteristics of broilers and pigs kept under heat stress conditions