Lactobacillus Acidophilus Regulates the Expression of MicroRNAs and Ameliorates the Symptoms of Acid-induced Ulcerative Colitis in Rats

Background and Objective: Ulcerative colitis (UC) is an unknown recurrent intestinal disease and a common cause of gastrointestinal disorders, which may lead to colorectal cancer if not diagnosed and treated in a timely manner. The beneficial effects of several probiotics in diseases like inflammatory bowel disease (IBD) have been investigated, although their mechanisms have not been yet fully understood. In this study, we investigated the possible association between the changes in the levels of the expression of miRNAs and the anti-inflammatory activity of the L. acidophilus as a probiotic model in Wistar rats suffering the acid-induced UC. Materials and Methods: Twenty rats were randomly divided into four groups. To induce colitis, the rats were briefly anesthetized, and 1 ml of acetic acid (4%) was injected into their rectum using a Foley catheter, as explained previously.  L. acidophilus was given orally (3×108 CCU/ml) for 10 days. The rats were monitored daily for clinical signs for 10 days. Following euthanasia, the macroscopic and microscopic pathological lesions in the intestinal tissues were examined. Additionally, the total RNA from specimens were extracted, and the expression levels of mRNAs for cytokines, including TNFα, IL-1β, IL-6, IL-10, IFN-γ, and the expression levels of miR-1, miR-155, miR-let7d, and miR-99a were determined using the qPCR method. Results: The clinical signs and pathological damages induced by acid were ameliorated in the rats receiving L. acidophilus compared with rats that did not receive it, as evidenced by improved clinical signs and results of immunohistochemistry and chemical assays. miRNAs, including miR-1, miR-99, miR-Let7d and miR-155 and changes in the expression of mRNAs, including TNFα, IL-1β, IL-6, IL-10 and IFN-γ were significant. Changes in the amount of myeloperoxidase, nitrite oxide, and malondialdehyde were also significant (P ≤ 0.05). In pathological examination, immune cell infiltration and COX2 were different in colitis and treatment groups. Conclusion: Therapeutic use of probiotics ameliorated UC by significantly changing the levels of miR-1, miR-99, miR-Let7d and miR-155.