scholarly journals Dietary Taxifolin Protects Against Dextran Sulfate Sodium-Induced Colitis via NF-κB Signaling, Enhancing Intestinal Barrier and Modulating Gut Microbiota

2021 ◽  
Vol 11 ◽  
Author(s):  
Jinxiu Hou ◽  
Mingyang Hu ◽  
Le Zhang ◽  
Ya Gao ◽  
Libao Ma ◽  
...  

Taxifolin is a natural antioxidant polyphenol with various bioactivities and has many beneficial effects on human gut health. However, little is known of its function on colitis. In this study, the protective effects of taxifolin on colitis symptoms, inflammation, signaling pathways, and colon microbiota were investigated using dextran sulfate sodium (DSS)-induced colitis mice. Intriguingly, pre-administration of taxifolin alleviated the colitis symptoms and histological changes of the DSS-challenged mice. Supplementation of taxifolin significantly inhibited the secretions of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 and significantly increased the secretions of IL-10, secretory immunoglobulin A, superoxide dismutase, and immunoglobulins (IgA, IgG, and IgM) in DSS-induced colitis mice. In addition, the activation of nuclear factor kappa B (NF-κB; p65 and IκBα) signaling was significantly suppressed by taxifolin supplementation. The expression of tight junction proteins (claudin-1 and occludin) was significantly increased by taxifolin. Moreover, 16S rDNA sequencing revealed that the DSS-induced changes of colon microbiota composition and microbial functions (amino acid metabolism and MAPK signaling) were restored by taxifolin, including the decreases of the abundances of Bacteroides, Clostridium ramosum, Clostridium saccharogumia, Sphingobacterium multivorum, and the ratio of Bacteroidetes/Firmicutes, and the increases of the abundances of Desulfovibrio C21 c20 and Gemmiger formicilis at species level. In conclusion, these results revealed that dietary taxifolin has a great potential to prevent colitis by inhibiting the NF-κB signaling pathway, enhancing intestinal barrier, and modulating gut microbiota.

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Qingbiao Xu ◽  
Mingyang Hu ◽  
Min Li ◽  
Jinxiu Hou ◽  
Xianghua Zhang ◽  
...  

Inflammatory bowel disease (IBD) is a chronic intestinal disorder threatening human health. Di-peptide alanyl-glutamine (Ala-Gln) has various beneficial effects on gut health. However, its role and functional mechanism in treating IBD are still not clear. Therefore, the protective effects of Ala-Gln and glutamine (Gln) on dextran sulfate sodium- (DSS-) induced colitic mice were investigated in this study. The results showed that oral supplementation of Ala-Gln or Gln significantly attenuated the colitis symptoms in mice, including body weight loss, colon length, disease activity index, histological scores, and tissue apoptosis. The concentrations of interleukin- (IL-) 1β, IL-6, tumor necrosis factor-α, and myeloperoxidase were significantly decreased, while the concentrations of immunoglobulins (IgA, IgG, and IgM) and superoxide dismutase were significantly increased by Ala-Gln or Gln supplementation. The expression of occludin and peptide transporter 1 (PepT1) was significantly increased by Ala-Gln or Gln. Interestingly, Ala-Gln had better beneficial effects than Gln in alleviating colitis. In addition, 16S rDNA sequencing showed that the DSS-induced shifts of the microbiome (community diversity, evenness, richness, and composition) in the mouse colon were restored by Gln and Ala-Gln, including Lactobacillus, Bacteroides_acidifaciens, Bacteroidales, Firmicutes, Clostridia, Helicobacter, and Bacteroides. Correspondingly, the functions of the microflora metabolism pathways were also rescued by Ala-Gln, including fatty acid metabolism, membrane transporters, infectious diseases, and immune system. In conclusion, the results revealed that Ala-Gln can prevent colitis through PepT1, enhancing the intestinal barrier and modulating gut microbiota and microflora metabolites.


Planta Medica ◽  
2021 ◽  
Author(s):  
Jiaqi Wu ◽  
Yuzheng Wu ◽  
Yue Chen ◽  
Mengyang Liu ◽  
Haiyang Yu ◽  
...  

AbstractUlcerative colitis has been recognized as a chronic inflammatory disease predominantly disturbing the colon and rectum. Clinically, the aminosalicylates, steroids, immunosuppressants, and biological drugs are generally used for the treatment of ulcerative colitis at different stages of disease progression. However, the therapeutic efficacy of these drugs does not satisfy the patients due to the frequent drug resistance. Herein, we reported the anti-ulcerative colitis activity of desmethylbellidifolin, a xanthone isolated from Gentianella acuta, in dextran sulfate sodium-induced colitis in mice. C57BL/6 mice were treated with 2% dextran sulfate sodium in drinking water to induce acute colitis. Desmethylbellidifolin or balsalazide sodium was orally administrated once a day. Biological samples were collected for immunohistological analysis, intestinal barrier function evaluation, cytokine measurement, and gut microbiota analysis. The results revealed that desmethylbellidifolin alleviated colon shortening and body weight loss in dextran sulfate sodium-induced mice. The disease activity index was also lowered by desmethylbellidifolin after 9 days of treatment. Furthermore, desmethylbellidifolin remarkably ameliorated colonic inflammation through suppressing the expression of interleukin-6 and tumor necrosis factor-α. The intestinal epithelial barrier was strengthened by desmethylbellidifolin through increasing levels of occludin, ZO-1, and claudins. In addition, desmethylbellidifolin modulated the gut dysbiosis induced by dextran sulfate sodium. These findings suggested that desmethylbellidifolin effectively improved experimental ulcerative colitis, at least partly, through maintaining intestinal barrier integrity, inhibiting proinflammatory cytokines, and modulating dysregulated gut microbiota.


2020 ◽  
Vol 8 (6) ◽  
pp. 845
Author(s):  
Soyoung Yeo ◽  
Hyunjoon Park ◽  
Eunsol Seo ◽  
Jihee Kim ◽  
Byoung Kook Kim ◽  
...  

Inflammatory bowel disease (IBD) is a group of conditions involving chronic relapsing-remitting inflammation of the gastrointestinal tract with an unknown etiology. Although the cause–effect relationship between gut microbiota and IBD has not been clearly established, emerging evidence from experimental models supports the idea that gut microbes play a fundamental role in the pathogenesis of IBD. As microbiome-based therapeutics for IBD, the beneficial effects of probiotics have been found in animal colitis models and IBD patients. In this study, based on the dextran sulfate sodium (DSS)-induced colitis mouse model, we investigated Lactobacillus rhamnosus strain LDTM 7511 originating from Korean infant feces as a putative probiotic strain for IBD. The strain LDTM 7511 not only alleviated the release of inflammatory mediators, but also induced the transition of gut microbiota from dysbiotic conditions, exhibiting the opposite pattern in the abundance of DSS colitis-associated bacterial taxa to the DSS group. Our findings suggest that the strain LDTM 7511 has the potential to be used as a probiotic treatment for IBD patients in comparison to L. rhamnosus GG (ATCC 53103), which has been frequently used for IBD studies.


2019 ◽  
Vol 117 ◽  
pp. 109200 ◽  
Author(s):  
Qiangqiang Li ◽  
Xinwen Liang ◽  
Nana Guo ◽  
Lin Hu ◽  
Maruthi Prasad E. ◽  
...  

2020 ◽  
Vol 11 (9) ◽  
pp. 7817-7829 ◽  
Author(s):  
Kangliang Sheng ◽  
Guanghui Zhang ◽  
Ming Sun ◽  
Shiman He ◽  
Xiaowei Kong ◽  
...  

Grape seed proanthocyanidin extract had the strongest efficacy on colitis through inhibiting inflammation and oxidative stress, protecting epithelial integrity, and gut microbiota modulation.


2021 ◽  
Vol 8 ◽  
Author(s):  
Xingwei Xiang ◽  
Qihong Jiang ◽  
Wan Shao ◽  
Jinhong Li ◽  
Yufang Zhou ◽  
...  

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.


2020 ◽  
Author(s):  
Cherng-Shyang Chang ◽  
Yi-Chu Liao ◽  
Chih-Ting Huang ◽  
Chiao-Mei Lin ◽  
Chantal Hoi Yin Cheung ◽  
...  

Abstract Background: Leaky gut and microbiota dysbiosis have been linked to many chronic inflammatory diseases. Strengthening the gut epithelial barrier is a novel but overlooked strategy for management of gut microbiota-associated illnesses. Results: Using the dextran sulfate sodium (DSS)-induced gut barrier injury-based colitis model, we found that DSS-induced weight loss, rectal bleeding, and colonic epithelium damage were ameliorated in dual-specificity phosphatase 6 (Dusp6)-deficient mice. These protective effects could be attributed to the enhanced colon barrier integrity conferred by Dusp6-deficiency. Consistently, DUSP6 mutation in Caco-2 cells elevated transepithelial electrical resistance, enhanced tight-junctions, and increased expression of microvilli-associated genes. DUSP6-deficient Caco-2 cells also showed increased mitochondrial oxygen consumption accompanied by altered glucose metabolism and decreased glycolysis. Remarkably, our microbiome analysis found that Dusp6-deficient mice harbored fewer pathobionts and facultative anaerobes and more obligate anaerobes than wild-type mice after DSS treatment. Our cohousing and fecal microbiota transplantation experiments demonstrated that the gut/fecal microbiota derived from Dusp6-deficient mice also conferred protection against colitis.Conclusion: We have thus identified Dusp6 deficiency as beneficial in enhancing gut barrier integrity, elevating epithelial phosphoxidation, and maintaining the gut microbiota eubiosis necessary to protect against colitis.


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