Polysaccharides derived from Shenling Baizhu San improve colitis via modulating tryptophan metabolism in mice.

Shenling Baizhu San has beneficial effects on the metabolism of the gut microbiota, however, the mechanisms underlying microbiota metabolites mediated anti-inflammation signaling are not well understood. Previously, we have demonstrated that supplementation with Shenling Baizhu San alleviated antibiotic-associated diarrhea (AAD). The current study intends to investigate the dynamic modulation of Shenling Baizhu San polysaccharides (SP) on colitis from the gut microbiota metabolites perspective. Administration of SP effectively relieved colitis induced by DSS in mice, including alleviating body weight loss, the downregulation of colon proinflammatory mediators, and the promotion of intestinal injury repair. Whereas, the efficacy was eliminated by antibiotics, which demonstrated that the efficacy of SP was dependent on the gut microbiota. Fecal microbiota transplantation (FMT) showed that the efficacy of SP can be transferred to gut microbiota. Serum metabolomics analysis showed that supplementation with SP significantly promoted tryptophan metabolism, which was consistent with the changed structure of the gut microbiota, including Bacteroides, Bifidobacterium and Ruminococcus regulated by SP. Especially, the tryptophan metabolites-kynurenine (KYN) activated the expression of amplifying aryl-hydrocarbon receptor (AhR) and Cyp1A1 to promote IL-10 expression in colon. These data suggested that SP positively affected colitis in mice by regulating tryptophan metabolic function of their gut microbiota.

Heat stress inhibits TLR4-NF-κB and TLR4-TBK1 signaling pathways in broilers infected with Salmonella Typhimurium.

With the global warming, the harm of heat stress (HS) to the breeding industry has become more common, which causes the decline of animal production performance and low immunity. This study aimed to analyze the effect of HS on the intestinal immune function of Salmonella-infected chickens. Fourteen-day-old broilers were divided into the following four groups of eight replicates: control (Control), heat stress (HS), Salmonella Typhimurium (ST), and heat stress + Salmonella Typhimurium (HS+ST). The broilers were subjected to a heat stress of 35 °C from 15 to 28 days of age. Salmonella Typhimurium (ST, 14028, 109 cfu/mL) was inoculated, via oral administration at 29 days of age, into ST and HS+ST group birds. On the 4th day after Salmonella Typhimurium administration, an increase in jejunum IgA levels was observed in chickens infected with Salmonella Typhimurium. Mechanistic regulation of TLR4-NFκB-NLRP3 and TLR4-TBK1 signaling by heat stress was evaluated in Salmonella Typhimurium-infected broilers. Heat stress markedly inhibited the expression of cytokines including TNF-α, IL-6, IL-1ß, NLRP3, caspase-1, NF-κB-p65, and p-NF-κB-p65, and the TLR4-TBK1 cytokines IFN-α, IFN-γ, p-IRF3, and p-TBK1 in jejunum of broilers infected with Salmonella Typhimurium. Collectively, our results demonstrate that heat stress can inhibit intestinal immune response by downregulating the expression of TLR4-NFκB-NLRP3 and TLR4-TBK1 signaling pathways in broilers infected with Salmonella Typhimurium.

Heat stress inhibits expression of the cytokines, and NF-κB-NLRP3 signaling pathway in broiler chickens infected with salmonella typhimurium.

High ambient temperature has potential influence on oxidative stress, or systemic inflammation affecting poultry production and immune status of chickens. Heat stress (HS) induces intestinal inflammation and increases susceptibility of harmful pathogens, such as Salmonella and Escherichia coli. Intestinal inflammation is a common result of body immune dysfunction. Therefore, we designed an experiment to analyze the effects of 35 ± 2 °C HS on salmonella infection in chickens through regulation of the immune responses. 40 broiler chickens were randomly divided into 4 groups: control group, heat stress (HS) group, salmonella typhimurium (ST) group and model group (heat stress + salmonella typhimurium, HS + ST). Birds in HS and model group were treated with 35 ± 2 °C heat stress 6 h a day and for 14 continuous days. Then, ST and model group birds were orally administrated with 1 mL ST inoculum (109 cfu/mL). Chickens were sacrificed at the 4th day after ST administration and ileum tissues were measured. We observed that heat stress decreased ileum TNF-α and IL-1ß protein expressions. Concomitantly heat stress decreased NLRP3 and Caspase-1 protein levels. The protein expressions of p-NF-κB-p65 and p-IκB-α in ileum. Heat stress also inhibited IFN-α, p-IRF3 and p-TBK1, showing a deficiency in the HS + ST group birds. Together, the present data suggested that heat stress suppressed intestinal immune activity in chickens infected by salmonella typhimurium, as observed by the decrease of immune cytokines levels, which regulated by NF-κB-NLRP3 signaling pathway.

Heat stress aggravates intestinal inflammation through TLR4-NF-κB signaling pathway in Ma chickens infected with Escherichia coli O157:H7.

Heat stress can decrease poultry performance indices, immune function, and intestinal development, which can reduce birds' innate protective mechanisms and may be more susceptible for pathogens. Ma chickens heat-stressed with 41°C for 12 h and recovered for 7 d had extremely low immunity. In this study, a susceptible chicken model induced by heat stress and then infected with Escherichia coli O157:H7 was established to explore the mechanisms of birds' intestinal immune function changes. Ma chickens in heat stress + E. coli (HS + E. coli) group were stressed at 41°C for 12 h and recovered for 7 d, then chickens in E. coli group and HS + E. coli group were orally administered with 1 mL E. coli O157:H7 (1 × 109 cfu/mL). Chickens were sacrificed at the fourth day after E. coli administration. Results showed that the HS + E. coli group had increased intestinal length and weight, had higher E. coli counts in cecum contents than the E. coli group. Heat stress also enhanced serum diamine oxidase and decreased IgA level in chickens infected by E. coli. Heat stress had protective effects in small intestinal morphology except for duodenum by using hematoxylin and eosin staining. Compared with the E. coli group birds, IL-1ß, TNF-α, and caspase-1 protein levels in the duodenum and ileum were significantly increased. Heat stress also can significantly enhance the gene and protein expression of Hsp70, TLR4, and NF-κB in the duodenum and ileum, respectively. The gene expression of Hsp70, TLR4, and NF-κB in the jejunum was not influenced, but the protein expression of Hsp70 and NF-κB was inhibited by heat stress. The results indicated heat stress can amplify the effect of E. coli on intestinal inflammatory injury of Ma chickens through increasing TLR4-NF-κB signaling pathway.