The gut microbiota is a complex community of microorganisms that inhabit the digestive tracts of humans, living in symbiosis with the host. Dysbiosis, characterized by an imbalance between the beneficial and opportunistic gut microbiota, is associated with several gastrointestinal disorders, such as irritable bowel syndrome (IBS); inflammatory bowel disease (IBD), represented by ulcerative colitis and Crohn’s disease; and colorectal cancer (CRC). Dysbiosis can disrupt the mucosal barrier, resulting in perpetuation of inflammation and carcinogenesis. The increase in some specific groups of harmful bacteria, such as Escherichia coli ( E. coli ) and enterotoxigenic Bacteroides fragilis (ETBF), has been associated with chronic tissue inflammation and the release of pro-inflammatory and carcinogenic mediators, increasing the chance of developing CRC, following the inflammation-dysplasia-cancer sequence in IBD patients. Therefore, the aim of the present review was to analyze the correlation between changes in the gut microbiota and the development and maintenance of IBD, CRC, and IBD-associated CRC. Patients with IBD and CRC have shown reduced bacterial diversity and abundance compared to healthy individuals, with enrichment of Firmicute s and Bacteroidetes . Specific bacteria are also associated with the onset and progression of CRC, such as Fusobacterium nucleatum , E. coli , Enterococcus faecalis , Streptococcus gallolyticus , and ETBF. Future research can evaluate the advantages of modulating the gut microbiota as preventive measures in CRC high-risk patients, directly affecting the prognosis of the disease and the quality of life of patients.
4-methylesculetin is one of the coumarin derivatives with great anti-oxidant and anti-inflammatory activities. Recent studies have shown that 4-methylesculetin has a promising potentiality to treat inflammatory diseases, especially those related to reactive oxygen species, as inflammatory bowel disease. Based on this, the present study aims to investigate the intestinal anti-inflammatory activity of 4-methylesculetin in dextran sulfate sodium (DSS) model. For this purpose, mice received DSS 5% for 5 days followed by 2 days of filtered tap water. Treated groups received orally 5 or 25 mg/kg of 4-methylesculetin daily since the first day. Macroscopic, microscopic and biochemical parameters were evaluated. 4-methylesculetin (25 mg/kg) improved microscopic parameters, decreased MPO activity, reduced the colonic levels of IL-6 and counteracted GSH depletion when compared with DSS-control group. Our results show the intestinal anti-inflammatory activity of 4-methylesculetin in DSS model, which is related to its antioxidant and anti-inflammatory properties. This way, 4-methylesculetin, is a new potential compound for treatment of both types of IBD.
Mucositis is one of the commonest side effects in cancer patients undergoing treatment with radiotherapy and/or chemotherapy, and it currently lacks appropriate and effective treatment. , a species of flowering herb from South America, contains spilanthol, an alkylamide that has several pharmacological properties, including anesthetic, analgesic, and anti-inflammatory activities. Therefore, the purpose of this work was to evaluate the effect of spilanthol in intestinal mucositis in Swiss mice induced by 5-fluorouracil (5-FU), an antineoplastic agent administered systemically for the treatment of many different cancers. The repeated administration of 5-FU resulted in intestinal mucositis and consequent decreased food intake, together with weight loss, in all the animals. Daily administration of spilanthol significantly lowered the severity of intestinal mucositis, reducing histopathological changes and increasing the villus height in the animals treated with spilanthol at a dosage of 30 mg/kg (p< 0.0044) compared to a group exposed only to 5-FU. A decrease of myeloperoxidase activity was also observed in the animals treated with 30 mg/kg of spilanthol (p < 0.05), although several pro-inflammatory cytokines were not quantifiable in any group. In conclusion, the data demonstrated that spilanthol effectively reduced inflammation in a mouse model of intestinal mucositis induced by 5-FU, and that the compound might be a promising therapeutic candidate for the prevention and treatment of this condition.
Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC) and comprises a chronic gastrointestinal tract disorder characterized by hyperactive and dysregulated immune responses to environmental factors, including gut microbiota and dietary components. An imbalance of the intestinal microbiota may contribute to the development and/or worsening of the inflammatory process. MicroRNAs (miRNAs) have been associated with various physiological processes, such as cell development and proliferation, apoptosis, and cancer. In addition, they play an important role in inflammatory processes, acting in the regulation of pro- and anti-inflammatory pathways. Differences in the profiles of miRNAs may represent a useful tool in the diagnosis of UC and CD and as a prognostic marker in both diseases. The relationship between miRNAs and the intestinal microbiota is not completely elucidated, but recently this topic has gained prominence and has become the target of several studies that demonstrate the role of miRNAs in the modulation of the intestinal microbiota and induction of dysbiosis; the microbiota, in turn, can regulate the expression of miRNAs and, consequently, alter the intestinal homeostasis. Therefore, this review aims to describe the interaction between the intestinal microbiota and miRNAs in IBD, recent discoveries, and perspectives for the future.
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