Project description:Inflammatory bowel disease, an intestinal relapsing inflammatory disease, not only impairs gastrointestinal function but also increases the chances of developing colon cancer. Currently, the effects of shrimp peptide (SP) in mice model of ulcerative colitis (UC) are still unclear. In particular, it is uncertain whether SP affects the gut flora with UC mice. In this study, we investigated the anti-inflammatory effects of SP on a dextran sulfate sodium (DSS)-induced mouse model of UC. Firstly, the molecular weight of SP was mainly distributed in the range of 180-1,000 Da (61.95% proportion), and the amino acid composition showed that SP contained 17 amino acids, of which, the essential amino acids accounted for 54.50%. In vivo, oral SP significantly attenuated the severity of colitis, such as diarrhea, weight loss, and rectal bleeding. Furthermore, treatment with SP remarkably ameliorated intestinal barrier integrity, thus lowering the levels of the inflammatory cytokines and ameliorating antioxidant indices and intestinal injury indicators in the serum and colon. Lastly, the cecal contents were used to sequence and analyze the 16S rRNA genes of bacteria. Results suggested that treatment with SP could restore the balance of intestinal flora in modeled mice by regulating the abundance of pathogenic and beneficial bacteria. Furthermore, SP could significantly improve intestinal flora dysfunction in mice with UC. In summary, our findings show that SP has a prophylactic and therapeutic effect in UC in vivo, thereby highlighting its broad medicinal applications.
Project description:As a known inhibitor of pyridoxal phosphate-dependent transaminase glutamic-oxaloacetic transaminase 1 (GOT1), aminooxyacetic acid (AOAA) has been pointed out to have potential pharmacological effects in antiepileptic, anticonvulsant, antibacterial, cancer cell proliferation inhibition, and acute myocardial infarction (MI) relief. However, its role in inflammatory bowel disease (IBD) has not been reported. Through the in vivo experiment of dextran sulfate sodium- (DSS-) induced colitis in mice, it was found that AOAA significantly attenuated the symptoms, signs, and pathological changes of colitis. In addition, AOAA treatment prevented gut barrier damages by enhancing the expression of zona occludens- (ZO-) 1, occludin, claudin-1, and E-cadherin and recovering the upregulation of the most abundant intermediate filament protein (vimentin). Moreover, the release of interleukin- (IL-) 1β, IL-6, and tumour necrosis factor- (TNF-) α was suppressed, yet the level of IL-10 was upregulated by AOAA treatment compared to the model group. Furthermore, it was shown that AOAA administration boosted M2-like phenotype and effectively reduced M1 macrophage phenotype in the lamina propria of mouse colonic epithelium. Similarly, the effect of AOAA was verified in vitro. AOAA effectively inhibited the classically activated M1 macrophage phenotype and proinflammatory cytokine (IL-1β, TNF-α, and IL-6) expression induced by lipopolysaccharide (LPS) and promoted M2-like phenotype. Collectively, this study reveals for the first time that short-term treatment of AOAA can significantly alleviate DSS-induced acute colitis by regulating intestinal barrier function and macrophage polarization, which provides a theoretical basis for the potential use of AOAA in the treatment of IBD.
Project description:A high-fat diet (HFD) is recognized as an important contributor to inflammatory bowel disease (IBD). However, the precise underlying mechanism of HFD on IBD remains elusive. This study aimed to investigate the potential mechanism by which HFD affects IBD using 16S rRNA-sequencing and RNA-seq technology. Results indicated that HFD-treated mice exhibited notable alternations in the structure and composition of the gut microbiota, with some of these alternations being associated with the pathogenesis of IBD. Analysis of the colon transcriptome revealed 11 hub genes and 7 hub pathways among control, DSS-induced colitis, and HFD + DSS-treated groups. Further analysis explores the relationship between the hub pathways and genes, as well as the hub genes and gut microbiota. Overall, the findings indicate that the impact of HFD on DSS-induced colitis may be linked to intestinal dysbiosis and specific genes such as Abca8b, Ace2, Apoa1, Apoa4, Apoc3, Aspa, Dpp4, Maob, Slc34a2, Slc7a9, and Trpm6. These results provide valuable insights for determining potential therapeutic targets for addressing HFD-induced IBD.
Project description:Salvianolic acid A (SAA) is an active phenolic acid derived from Salvia miltiorrhiza Bunge (Danshen). To explore whether SAA has a therapeutic effect against inflammatory bowel disease (IBD), an acute colitis model was induced in rats by administering 3% dextran sodium sulphate (DSS) for one week. SAA in doses of 4 and 8 mg/kg/day was given by tail vein injection during DSS administration. Both dosages of SAA ameliorated the colitis symptoms, with decreases observed in the disease activity index. A high dosage of SAA (8 mg/kg/day) promoted a longer colon length and an improved colonic tissue structure, compared with the DSS-treated rats not receiving SAA. SAA dose-dependently decreased colonic gene expression of pro-inflammatory cytokines (IL-1β, MCP-1 and IL-6). Moreover, a high dosage of SAA protected against DSS-induced damage to tight junctions (TJ) in the rats’ colons, by increasing TJ-related gene expression (ZO-1 and occuldin). Finally, using 16S rRNA phylogenetic sequencing, we found that SAA modulated gut microbiota imbalance during colitis by increasing the gut microbial diversity as well as selectively promoting some probiotic populations, including Akkermansia spp. Our study suggests that SAA is a promising candidate for the treatment of IBD.
Project description:Dietary polyphenols are reported to alleviate colitis by interacting with gut microbiota which plays an important role in maintaining the integrity of the intestinal barrier. As a type of dietary polyphenol, whether ligustroside (Lig) could alleviate colitis has not been explored yet. Here, we aimed to determine if supplementation of ligustroside could improve colitis. We explored the influence of ligustroside intake with different dosages on colitis induced with dextran sulfate sodium (DSS). Compared to the DSS group, supplementation of ligustroside could reduce body weight (BW) loss, decrease disease activity indices (DAI), and relieve colon damage in colitis mice. Furthermore, ligustroside intake with 2 mg/kg could decrease proinflammatory cytokine concentrations in serum and increase immunoglobulin content and antioxidant enzymes in colon tissue. In addition, supplementation of ligustroside (2 mg/kg) could reduce mucus secretion and prevent cell apoptosis. Also, changes were revealed in the bacterial community composition, microbiota functional profiles, and intestinal metabolite composition following ligustroside supplementation with 2 mg/kg using 16S rRNA sequencing and non-targeted lipidomics analysis. In conclusion, the results showed that ligustroside was very effective in preventing colitis through reduction in inflammation and the enhancement of the intestinal barrier. Furthermore, supplementation with ligustroside altered the gut microbiota and lipid composition of colitis mice.
Project description:Oleoylethanolamide (OEA) is an endogenous fatty acid ethanolamide known for its anti-inflammatory effects and its influence on gut microbiota composition; however, the effects of OEA in inflammatory bowel disease (IBD) remain unknown. During in vitro experiments, OEA downregulated the expression of tumor necrosis factor (TNF)-α and reduced phosphorylation of inhibitor of kappa (Iκ) Bα induced by lipopolysaccharide in human embryonic kidney cells. Moreover, OEA downregulated the expression of interleukin (IL)-8 and IL-1β and inhibited the phosphorylation of IκBα and p65 induced by TNF-α in human enterocytes (Caco-2). The effect of OEA in reducing the expression of IL-8 was blocked by the peroxisome proliferator-activated receptor (PPAR)-α antagonist. During in vivo experiments on rats, colitis was induced by the oral administration of 8% dextran sulfate sodium from day 0 through day 5, and OEA (20 mg/kg) was intraperitoneally injected once a day from day 0 for 6 days. OEA administration significantly ameliorated the reduction in body weight, the increase in disease activity index score, and the shortening of colon length. In rectums, OEA administration reduced the infiltration of macrophages and neutrophils and tended to reduce the histological score and the expression of inflammatory cytokines. Administration of OEA produced significant improvement in a colitis model, possibly by inhibiting the nuclear factor kappa B signaling pathway through PPAR-α receptors. OEA could be a potential new treatment for IBD.
Project description:Ulcerative colitis is one of the main gastrointestinal diseases that threaten human health. This study investigated the effect of Limosilactobacillus fermentum HFY06 (LF-HFY06) on dextran sulfate sodium (DSS)-induced murine colitis. The protective effect of LF-HFY06 was evaluated by examining the length and histopathological sections of colon, related biochemical indicators, and genes related to inflammation. Direct and microscopic observations showed that LF-HFY06 increased the length of the colon and ameliorated the pathological damage induced by DSS. The biochemical indicators showed that LF-HFY06 enhanced the activities of antioxidant enzymes total superoxide dismutase (T-SOD) and catalase (CAT) in serum, while reducing the level of malondialdehyde (MDA). It was also observed that the serum inflammatory cytokines levels of tumor necrosis factor-α (TNF-α), interferon (IFN)-γ, interleukin (IL)-1β, IL-6, and IL-12 were decreased, and the anti-inflammatory cytokine IL-10 level was increased. The qPCR experiment revealed that LF-HFY06 downregulated the mRNA expression levels of nuclear factor-κB-p65 (Rela), Tnf, Il 1b, Il 6, and prostaglandin-endoperoxide synthase 2 (Ptgs2) in colon tissues, and upregulated the mRNA expression of NF-κB inhibitor-α (Nfkbia) and Il 10. These data indicated that LF-HFY06 inhibited inflammation through the NF-κB signaling pathway to prevent the occurrence and development of colitis. This research demonstrates that probiotics LF-HFY06 have the potential to prevent and treat colitis.
Project description:Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), characterized by the gut mucosal ulceration. Growing evidence indicates that dysregulation of immune response to the commensal microbiota involves the pathogenesis of IBD. Previous studies have demonstrated the favorable probiotic effects of fermented rice extracts through triple fermentation with Saccharomyces cerevisiae and Weissella cibaria (FRe). Thus, the therapeutic potential of FRe for UC was examined. Dextran sodium sulfate UC mice model was orally administered distilled water as a control, sulfasalazine, or FRe at 300, 200, and 100 mg/kg, once a day for a week. The UC control exhibited body weight loss, bloody stools, and colonic shortening. However, the FRe, especially at 300 mg/kg, led to a reduction in weight loss, disease activity index scores, and colon weight, and an increase in colorectal length. The histopathological analyses revealed mild changes involved in the colonic crypt and mucosal damages in the FRe groups, along with inhibited inflammation. Indeed, the FRe reduced neutrophil infiltration and production of proinflammatory cytokines (i.e., tumor necrosis factor-α, interleukin-6/-8). This was accompanied by the down-regulation of nuclear factor-kappa B. The gene expression responsible for the intestinal barrier integrity (i.e., Zonna occludens-1/-2, Claudin-1, Occludin, Mucin-1/-2) was up-regulated in the FRe groups. In addition, the FRe reduced lipid peroxidation and enhanced antioxidant activity. Interestingly, the microbiota dysbiosis was attenuated in the FRe groups, and the number of beneficial bacteria, Lactobacilli and Bifidobacteria, was increased. It suggests that the FRe potently ameliorate UC as a functional food.
Project description:Although low-dose lactulose has shown a good theoretical foundation for the treatment of ulcerative colitis (UC) in previous studies, the exact effects and mechanism remain unclear. The rats were randomly distributed into 5 groups, i.e., normal drinking water was provided for an initial 14 days in blank control group, 4% dextran sulfate sodium was used for modeling in the remaining 4 groups. During the 15-24th day, rats in the blank control group were administered with 0.9% saline (0.5 ml/d) by gavage. In the rest 4 groups, rats were administered 0.9% saline (0.5 ml/d, UC model), mesalazine (400 mg/kg/d), lactulose (1000 mg/kg/d), and lactulose + mesalazine (two-drug combination) by gavage. In addition to symptoms and pathological changes, serum IL-6, TNF-α, and High-sensitivity C-reactive protein(Hs-CRP) by ELISA analysis, mRNA and protein expression levels of TLR-2, TLR-4, Nuclear factor-κB(NF-κB), IL-6, and TNF-α in colon tissues by RT-qPCR and WB analyses respectively. Meanwhile, short-chain fatty acid(SCFAs) and intestinal flora were analyzed. Low-dose lactulose improved symptoms (diarrhea, blood in stool, weight loss) and pathological inflammation. In addition to serum IL-6, TNF-α, and Hs-CRP, the mRNA and protein expression levels of TLR-2, TLR-4, NF-κB, IL-6 and TNF-α in the colon were down-regulated with the intervention of lactulose.Meanwhile, lactulose decreased the ileocecal PH, increased SCFAs and altered the intestinal flora. Low-dose lactulose may be beneficial to UC by regulating TLRs/NF-κB pathway, reducing ileocecal PH, increasing SCFAs, regulating intestinal flora and improving the intestinal mucosal barrier. Meanwhile, low-dose lactulose and mesalazine may have additive effects upon combination.
Project description:Epidemiological studies have indicated that obesity is an independent risk factor for colitis and that a high-fat diet (HFD) increases the deterioration of colitis-related indicators in mice. Melatonin has multiple anti-inflammatory effects, including inhibiting tumor growth and regulating immune defense. However, the mechanism of its activity in ameliorating obesity-promoted colitis is still unclear. This study explored the possibility that melatonin has beneficial functions in HFD-induced dextran sodium sulfate (DSS)-induced colitis in mice. Here, we revealed that HFD-promoted obesity accelerated DSS-induced colitis, while melatonin intervention improved colitis. Melatonin significantly alleviated inflammation by increasing anti-inflammatory cytokine release and reducing the levels of proinflammatory cytokines in HFD- and DSS-treated mice. Furthermore, melatonin expressed antioxidant activities and reversed intestinal barrier integrity, resulting in improved colitis in DSS-treated obese mice. We also found that melatonin could reduce the ability of inflammatory cells to utilize fatty acids and decrease the growth-promoting effect of lipids by inhibiting autophagy. Taken together, our study indicates that the inhibitory effect of melatonin on autophagy weakens the lipid-mediated prosurvival advantage, which suggests that melatonin-targeted autophagy may provide an opportunity to prevent colitis in obese individuals.