Chronic heat stress induces the disorder of gut transport and immune function associated with endoplasmic reticulum stress in growing pigs

Although high temperatures influence gut health, data on underlying mechanisms remains scant. Using a pig model, this study performed a global analysis on how chronic heat stress affects the transport and immune function of the gut through transcriptome, proteome, microbial diversity and flow cytometry. A total of 27 pigs with similar body weights were assigned into 3 groups, control (Con) group (23 °C), chronic heat stressed (HS) group (33 °C), and pair-fed (PF) group, in a controlled environment for 21 days. Our results showed that pigs in the HS group had reduced growth performance and diminished height of ileal villi (P < 0.01). Transcriptome and proteome analyses demonstrated notable modification of expression of nutrients and ion transport-related transporters and gut mechanical barrier-related genes by chronic heart stress (P < 0.05), suggesting damage of transport functions and the gut barrier. Chronic heat stress-induced endoplasmic reticulum stress also increased the synthesis of misfolded proteins, leading to upregulation of misfolded protein degradation and synthesis, as well as vesicle transport disorder (P < 0.05). Energy supply processes were enhanced in the mitochondrion (P < 0.05) to maintain biological processes with high energy demands. Furthermore, chronic heat stress activated complement cascade response-related genes and proteins in the gut mucosa (P < 0.05). Our flow cytometry assays showed that the proportion of gut lymphocytes (CD4+ T cells, T cells, B cells in Peyer's patch lymphocytes and CD4+ CD25+ T cells in intraepithelial lymphocytes) were significantly altered in the HS group pigs (P < 0.05). In addition, the occurrence of gut microbial dysbiosis in the HS group pigs was characterized by increased potential pathogens (e.g., Asteroleplasma, Shuttleworthia, Mycoplasma) and suppression of beneficial bacteria (e.g., Coprococcus and Aeriscardovia), which are associated with gut immune function. Altogether, our data demonstrated that chronic heat stress induced gut transport and immune function disorder associated with endoplasmic reticulum stress in growing pigs.