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The pathological mechanisms of gastrointestinal disorders, including inflammatory bowel disease (IBD), in pigs are poorly understood. We report the induction of intestinal inflammation in heat-stressed (HS) pigs, fecal microbiota transplantation from pigs to mice, and explain the role of microorganisms in IBD. 24 adult pigs were subjected to HS (34 ± 1 °C; 75–85% relative humidity for 24h) while 24 control pigs (CP) were kept at 25 ± 3°C and the same humidity. Pigs were sacrificed on days 1, 7, 14, 21. Colonic content microbiome analyses were conducted. Pseudo-germ-free mice were fed by gavage with fecal microbiota from HS-pigs and CP to induce pig-like responses in mice. From 7 d, HS-pigs exhibited fever and diarrhea, and significantly lower colonic mucosal thickness, crypt depth/width, and goblet cell number. Compared with each control group, the concentration of cortisol in the peripheral blood of HS pigs gradually increased, significantly so on days 7, 14, and 21 (P < 0.01). While the concentration of LPS in HS pigs' peripheral blood was significantly higher on days 7, 14 (P < 0.01), and 21 (P < 0.05) compared with that of the control group. The colonic microbiome composition of HS-pigs was different to that of CP. By day 14, opportunistic pathogens (e.g., Campylobacterales) had increased in HS-pigs. The composition of the colonic microbiome in mice administered feces from HS-pigs was different from those receiving CP feces. Bacteroides were significantly diminished, Akkermansia were significantly increased, and intestinal damage and goblet cell numbers were higher in mice that received HS-pig feces. Moreover, we verified the relevance of differences in the microbiota of the colon among treatments. Heat stress promotes changes in gut microbiome composition, which can affect the colonic microbial structure of mice through fecal microbiota transplantation; the molecular mechanisms require further investigation. This study enhanced our understanding of stress-induced inflammation in the colon and the increase in diarrhea in mammals subjected to prolonged HS. Our results provide useful information for preventing or ameliorating deficits in pig production caused by prolonged exposure to high temperatures.

Tea tree oil (TTO) exhibits a potent antioxidant, antibacterial, and anti-inflammatory activity and is commonly used in skincare products. However, it is not clear whether TTO can protect gut barrier damage in inflammatory bowel disease (IBD) patients. Herein, we report the impact of terpinen-4-ol (TER, the primary constituent of TTO), on lipopolysaccharide (LPS)-induced intestinal epithelial cell barrier function impairment in intestinal porcine epithelial cell lines (IPEC-J2) and dextran sulfate sodium (DSS)-induced IBD in mice. TER protected against LPS-induced damage in IPEC-J2 cells in vitro and attenuated DSS-induced colitis in vivo. Added TER promoted the tight junction (TJ) proteins expressing in vitro and in vivo and attenuated the LPS-induced upregulation of ERK phosphorylation in IPEC-J2 cells. However, when an inhibitor of ERK phosphorylation was added, TER did not promote the expression of TJ protein, denoting that the ERK signaling pathway mediates the upregulation of TJ proteins. Our data may propose the potential application of TER in treating IBD.

Herein, we assessed the anti-inflammatory and intestinal barrier protective effects of butyrolactone-I (BTL-1), derived from the coral-derived endophytic fungus (Aspergillus terreus), using the LPS-induced IPEC-J2 inflammation model and the DSS-induced IBD model in mice. In IPEC-J2 cells, pretreatment with BTL-I significantly inhibited TLR4/NF-κB signaling pathway and JNK phosphorylation, resulting in the decrease of IL-1β and IL-6 expression. Interestingly, BTL-1 pretreatment activated the phosphorylation of ERK and P38, which significantly enhanced the expression of TNF-α. Meanwhile, BTL-1 pretreatment upregulated tight junction protein expression (ZO-1, occludin, and claudin-1) and maintained intestinal barrier and intestinal permeability integrity. In mice, BTL-1 significantly alleviated the intestinal inflammatory response induced by DSS, inhibited TLR4/NF-κB signaling pathway, and MAPK signaling pathway, thus reducing the production of IL-1, IL-6, and TNF-α. Further, the expression of tight junction proteins (ZO-1, occludin, and claudin-1) was upregulated in BTL-1 administrated mice. Therefore, it has been suggested that butyrolactone-I alleviates inflammatory responses in LPS-stimulated IPEC-J2 and DSS-induced murine colitis by TLR4/NF-κB and MAPK signal pathway. Thereby, BTL-1 might potentially be used as an ocean drug to prevent intestinal bowel disease.

Heat stressed pigs show typical characteristics of inflammatory bowel disease (IBD). However, little is known about the pathogenesis of heat stress (HS)-induced IBD in pigs. In this study, we determined the effects of HS on colon morphology, intestinal microbiota diversity, transcriptome genes (transcripts), and short chain fatty acids (SCFAs) metabolism in pigs. In addition, the correlation among these parameters was analyzed by weighted gene co-expression network analysis. Results showed that the liver and kidney functions related to blood biochemical indexes were partially changed in pigs under HS. Furthermore, the levels of diamine oxidase and D-lactic acid were significantly increased, whereas the levels of secretory immunoglobulin A were decreased. The integrity of colonic tissue was damaged under HS, as bleeding, lymphatic infiltration, and villi injury were observed. The concentrations of SCFAs in the colon, such as acetic acid and butyric acid, were decreased significantly. In addition, the composition of colon microbiota, such as decrease in Lactobacillus johnsonii, Lactobacillus reuteri and increase in Clostridium sensu stricto 1 of day 7 and 14 while under HS. These changes were associated with changes in the concentration of SCFAs and biochemical indexes above mentioned. Differentially expressed genes were enriched in the nucleotide-binding oligomerization domain-like receptor signaling pathway, Th17 cell differentiation, and IBD pathway, which were also associated with the changes in SCFAs. Thus, the structure, diversity of intestinal microorganisms, and changes in the levels of SCFAs in colon of heat stressed pigs changed significantly, contributing to the activation of immune response and inflammatory signal pathways and causing abnormal physiological and biochemical indexes and intestinal mucosal damage. These results highlight the interconnections between intestinal microbiota, SCFAs, and immune response and their role in the pathogenesis of stress induced IBD therapy.