Curcumin Alleviates Dextran Sulfate Sodium‐Induced Colitis in Mice Through Regulating Gut Microbiota

Abstract

Scope: Curcumin is a natural polyphenol compound with multiple pharmacologic activities. The present study aims to explore the potential therapeutic properties of curcumin on intestinal inflammatory diseases, including its anti-inflammatory, antioxidant, and anti-apoptotic properties, as well as their associations with altered intestinal microbiome. Methods and Results: DSS, i.e., Dextran Sulfate Sodium, (3%) is administered to C57BL/6J mice in the drinking water daily for 6 days in DSS and curcumin groups. Then, mice in curcumin groups are orally administered with 50 or 150 mg kg -1 curcumin for 7 days. On day 13, mice are sacrificed. Results show that oral administration with curcumin relieves macroscopic pathological manifestations, e.g., colon length and histological change. Moreover, it enhances intestinal barrier via increasing expression of tight junction proteins, e.g., occludin, ZO-1, claudin-3; alleviates DSS-induced intestinal apoptosis via suppressing caspase-3 pathway; mitigates intestinal inflammation via inhibiting the MAPK/NF𝜿B/STAT3 pathway. It is also noticed that curcumin is beneficial for modulating abundance of some specific bacteria, including Akkermansia, Coprococcus, Roseburia, and Turicibacter, as well as families such as F16, Enterococcaceae, and Aerococcaceae. Most of the altered bacteria by curcumin are highly correlated with colitis-associated parameters. Conclusion: Curcumin shows therapeutic potential against colitis. It may be served as an alternative medicine or adjuvant therapy in the treatment of colitis.

Vitexin Protects against Dextran Sodium Sulfate-Induced Colitis in Mice and Its Potential Mechanisms

“…We found that DSS treated in mice could significantly increase the relative abundance of pathogenic bacteria such as Proteobacteria , Enterobacteriaceae , Enterobacteriales , Gammaproteobacteria , and Enterococcus as compared with the control group. It is reported that high abundances of Proteobacteria , Enterobacteriacea , and Enterococcus microbiota are closely related to inflammatory activation. , Meanwhile, the lower abundances of Bacteroidia , Clostridia , and Roseburia were observed in the DSS group, these results were consistent with previous reports. Interesting, vitexin treatment in DSS-induced colitis mouse model had an inverse effect on gut microbiota structure, and significantly increased the abundance of protective symbiotic bacteria.…”

“…It is reported that high abundances of Proteobacteria, Enterobacteriacea, and Enterococcus microbiota are closely related to inflammatory activation. 9,42 Meanwhile, the lower abundances of Bacteroidia, Clostridia, and Roseburia were observed in the DSS group, these results were consistent with previous reports. Interesting, vitexin treatment in DSS-induced colitis mouse model had an inverse effect on gut microbiota structure, and significantly increased the abundance of protective symbiotic bacteria.…”

“…Ulcerative colitis (UC), an idiopathic inflammatory disease in the colonic mucosa, which begins in the rectum and usually extends proximally through part or the entire colon in a continuous manner . Accumulated evidence indicate that inflammation, intestinal barrier disorder, and intestinal flora disturbance are contributed to the pathogenesis of UC. ,, Similarly, drugs that suppress inflammation, rebuild gut barrier and gut microbiota have shown beneficial therapeutic effects on UC. In the present study, we explored the effect of vitexin on alleviating DSS-induced acute ulcerative colitis mouse model and further investigated its mechanism.…”

“…Accumulated evidence showed that the imbalance of proinflammatory and antiinflammatory cytokines in IBD can impede the elimination of inflammation, moreover, it perpetuates the disease and destroys colonic mucosal tissue . Notably, pro-inflammatory cytokines (such as IL-1β, IL-6, and TNF-α) are transcriptionally regulated by intracellular signaling molecules, including the NF-κB, STAT. , The activation of this signaling can aggravate the accumulation of pro-inflammatory cytokine in colon tissues, which can further inhibit the expressions of tight junction proteins to increase intestinal permeability and impair intestinal barrier function . In this study, we found that 5-ASA or vitexin administration significantly suppressed the infiltration of IL-1β, IL-6, and TNF-α cytokines in colon tissues.…”

“…Increasing epidemiological investigations have indicated that gut microbiota composition are involved in the pathogenesis of UC . It is reported that gut microbiota dysfunction is common in IBD patients or colitis animals models, and as compared with those of noncolitis control samples, the bacterial composition of colitis samples shows a significant increase in pathogenic bacteria (such as Enterobacteriaceae , Fusobacterium species , and Veillonellaceae ) or a dramatic decrease in probiotic bacteria (such as Roseburia and Bifidobacterium species ). − Multiple studies evidence that the increased pathogenic bacteria in IBD patients not only can directly invade and damage intestinal epithelial cells to induce intestinal mucosal inflammation but also can secrete enterotoxin to increase intestinal permeability . Moreover, probiotics, also an important component of the gut microbiota, are widely used to regulate intestinal flora imbalance to improve IBD .…”