Elevated Systemic and Intestinal Inflammatory Response Are Associated With Gut Microbiome Disorder After Cardiovascular Surgery.

Systemic inflammatory response after cardiovascular surgery is associated with poor prognosis, to which gut barrier impairment is related. To investigate whether perioperative changes of the gut microbiome are associated with systemic and intestinal inflammatory response, we examined changes of the gut microbiome, intestinal homeostasis, and systemic inflammatory response in cardiovascular patients before (Pre) surgery and on the first defecation day [postoperative time 1 (Po1)] or a week [postoperative time 2 (Po2)] postsurgery. Markedly, the enhanced systemic inflammatory response was observed in Po1 and Po2 compared with that in Pre. In line with inflammatory response, impaired gut barrier and elevated gut local inflammation were observed in Po1 and Po2. Microbiome analysis showed a remarkable and steady decline of alpha diversity perioperatively. In addition, microbial composition in the postoperation period was characterized by significant expansion of Enterococcus along with a decrease in anaerobes (Blautia, Faecalibacterium, Bifidobacterium, Roseburia, Gemmiger, [Ruminococcus], and Coprococcus), which were typically health-associated bacteria. Spearman correlation analysis showed microbiome disorder was associated with enhanced systemic inflammatory response and intestinal dysbiosis. These results suggest that microbiome disorder was related to disturbed gut homeostatic and subsequently elevates plasma endotoxin and systemic inflammatory response after cardiovascular surgery. This study not only highlights gut microbiome would be considered in future clinical practice but also proposes a promising perspective of potential diagnostic and therapeutic options for perioperative management of cardiovascular surgery patients.

GPA peptide inhibits NLRP3 inflammasome activation to ameliorate colitis through AMPK pathway.

Ulcerative colitis (UC) is a chronic and idiopathic inflammatory disease that affects the colon, resulting in immune dysregulation and the production of large amounts of pro-inflammatory cytokines. Pyroptosis and NLRP3 inflammasome are associated with various kinds of inflammatory diseases including colitis. The purpose of this study is to investigate the protective effects and regulatory mechanism of Gly-Pro-Ala (GPA) peptide on DSS-induced colitis. In vivo, we find GPA peptide could exert anti-inflammatory effects on DSS-induced mice colitis, and its anti-inflammatory effects are abolished in NLRP3-/- mice. In macrophage, GPA suppresses the assembly of NLRP3 inflammasome and GSDMD cleavage. Furthermore, GPA maintains mitochondrial homeostasis through inhibiting ROS, mtDNA and NLRP3 mitochondrial localization, with other signals related to NLRP3 inflammasome unaffected. Furthermore, the inhibitory effects of GPA on reactive oxygen species (ROS) are found to be achieved by increasing AMPK phosphorylation. Our results suggest that GPA inhibits NLRP3 inflammasome activation through increasing AMPK phosphorylation to suppress ROS, and can be applied in the prevention of colitis through targeting NLRP3.

FSGHF3 and peptides, prepared from fish skin gelatin, exert a protective effect on DSS-induced colitis via the Nrf2 pathway.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. We previously found that fish skin gelatin hydrolysate fraction 3 (FSGHF3), isolated from fish skin gelatin hydrolysate, could exert antioxidant effects and maintain tight junctions in IPEC-J2 cells. Further HPLC-ESI-QqQ-MS results revealed that this fraction mainly included some peptides. Here, we aim to evaluate the effects of FSGHF3 and peptides in the mice model of dextran sodium sulfate (DSS)-induced colitis and LPS induced inflammation in IECs. The results show that FSGHF3 significantly ameliorates the clinical symptoms of DSS-induced colitis in mice, such as weight loss, disease activity index (DAI), colon shortening, spleen hypertrophy, histological scores, and MPO activity. FSGHF3 and peptide treatment inhibits pro-inflammatory cytokine production, leading to the maintenance of intestinal architecture in vivo and in vitro. Meanwhile, FSGHF3 and peptide treatment promotes antioxidant enzyme expression via activating Nrf2, which results in the removal of ROS and inhibition of NF-κB activation. Overall, our results suggest that FSGHF3 and peptides may be promising potential candidates for the alleviation of colitis.