Heat stress in pigs and broilers: role of gut dysbiosis in the impairment of the gut-liver axis and restoration of these effects by probiotics, prebiotics and synbiotics

Abstract

Heat stress is one of the most challenging stressors for animal production due to high economic losses resulting from impaired animal's productivity, health and welfare. Despite the fact that all farm animal species are susceptible to heat stress, birds and pigs are particularly sensitive to heat stress due to either lacking or non-functional sweat glands. Convincing evidence in the literature exists that gut dysbiosis, a term used to describe a perturbation of commensal gut microbiota, develops in broilers and pigs under heat stress. Owing to the protective role of commensal bacteria for the gut barrier, gut dysbiosis causes a disruption of the gut barrier leading to endotoxemia, which contributes to the typical characteristics of heat stressed broilers and growing and growing-finishing pigs, such as reduced feed intake, decreased growth and reduced lean carcass weight. A substantial number of studies have shown that feeding of probiotics, prebiotics and synbiotics is an efficacious strategy to protect broilers from heat stress-induced gut barrier disruption through altering the gut microbiota and promoting all decisive structural, biochemical, and immunological elements of the intestinal barrier. In most of the available studies in heat stressed broilers, the alterations of gut microbiota and improvements of gut barrier function induced by feeding of either probiotics, prebiotics or synbiotics were accompanied by an improved productivity, health and/or welfare when compared to non-supplemented broilers exposed to heat stress. These findings indicate that the restoration of gut homeostasis and function is a key target for dietary interventions aiming to provide at least partial protection of broilers from the detrimental impact of heat stress conditions. Despite the fact that the number of studies dealing with the same feeding strategy in heat stressed pigs is limited, the available few studies suggest that feeding of probiotics might also be a suitable approach to enhance productivity, health and welfare in pigs kept under heat stress conditions.

Keywords: Broilers; Commensal bacteria; Gut dysbiosis; Heat stress; Pigs; Prebiotics; Probiotics; Synbiotics.

Fig. 1

Important mechanisms of commensals involved in colonization resistance. The commensals in the gut play a key role in preventing the expansion of potential pathogens, thereby, contributing to colonization resistance. The most important mechanisms of commensals involved in colonization resistance comprise: (A) Commensals provide a direct barrier to colonization by pathogens through competing for space and nutrients; (B) Commensals continuously stimulate pathogen recognition receptors (PRR), like Toll-like receptors (TLR), on intestinal epithelial cells (IEC) to secrete protective mucins (MUC) and antimicrobial peptides (AMP); (C) Commensals contribute to adaptive immunity by stimulating secretion of secretory immunoglobulin A (IgA) which provides protection against pathogens by crosslinking of pathogenic bacteria and neutralizing bacterial toxins; (D) Commensals generate microbial fermentation products, such as butyrate, which has trophic effects on the intestinal mucosa, thereby, enhancing the intestinal barrier

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

Fig. 3

Efficacy of dietary probiotics, prebiotics, synbiotics and postbiotics to restore the gut-liver axis function, metabolic health and performance in broilers and pigs exposed to heat stress. Convincing evidence exists that feeding of probiotics (mainly Lactobacillus (L.) ssp. and Bifidobacterium (B.) ssp.), prebiotics (cello-, fructo-, galacto- and mannan-oligosaccharides) and synbiotics (different probiotic mixtures with either cello- or galacto-oligosaccharides) is an efficacious strategy to protect broilers from heat stress-induced gut dysbiosis, impairment of gut barrier integrity and gut morphology and function, hepatic inflammation, hypothalamic inflammation, impairment of metabolic health and reduction of performance. In addition, results from a few studies show that dietary postbiotics based on inactivated L. plantarum strains alleviate the adverse impact of heat stress in broilers. In pigs, only a few studies demonstrated that feeding of probiotics (probiotic mixtures or a specific Saccharomyces cerevisiae strain) is also a suitable approach to protect from heat stress-induced impairment of gut integrity and function, metabolic health and performance. However, no studies are available in pigs investigating the efficacy of prebiotics, synbiotics and postbiotics on gut health, metabolic health and productivity under heat stress