Amelioration of dextran sodium sulfate-induced colitis in mice by Rhodobacter sphaeroides extract

Abstract

Bacteria can produce some compounds in response to their environment. These compounds are widely used in cosmetic and pharmaceutical applications. Some probiotics have immunomodulatory activities and modulate the symptoms of several diseases. Autoimmune diseases represent a complex group of conditions that are thought to be mediated through the development of autoreactive immunoresponses. Inflammatory bowel disease (IBD) is common autoimmune disease that affects many individuals worldwide. Previously, we found that the extracts of Rhodobacter sphaeroides (Lycogen) inhibited nitric oxide production and inducible nitric-oxide synthase expression in activated macrophages. In this study, the effect of Lycogen, a potent anti-inflammatory agent, was evaluated in mice with dextran sodium sulfate (DSS)-induced colitis. Oral administration of Lycogen reduced the expressions of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) in female BABL/c mice. In addition, the increased number of bacterial flora in the colon induced by DSS was amelirated by Lycogen. The histological score of intestinal inflammation in 5% DSS-treated mice after oral administration of Lycogen was lower than that of control mice. Meanwhile, Lycogen dramatically prolonged the survival of mice with severe colitis. These findings identified that Lycogen is an anti-inflammatory agent with the capacity to ameliorate DSS-induced colitis.

Figure 1

Effects of Lycogen™ on cytokine induction in DSS-induced colitis. The mice with colitis were orally administered with Lycogen™ (1 mg/kg) for six consecutive days after DSS induction. (A) TNF-α and (B) IL-1 β levels in the sera were measured by ELISA at day 6 (mean ± SD, n = 4). Significance of differences between groups for continuous variables was assessed using the Student t-test. * p < 0.05; ** p < 0.01. Each experiment was repeated three times with similar results.

Figure 2

Effect of Lycogen™ on DSS-induced colitis mice. (A) The mice with colitis were orally administered with Lycogen™ (1 mg/kg) for six consecutive days after DSS induction and the body weights of mice were determined (means ± SD, n = 6). p < 0.01 for colitis mice treated with Lycogen™ versus colitis mice treated with PBS (B) Kaplan-Meier survival curves on day 14 are shown. (mean ± SD, n = 6) Significance of differences between groups for continuous variables was assessed using the Student t-test. The mice survival analysis was performed using the Kaplan-Meier survival curve and log-rank test. ** p < 0.01; *** p < 0.001.

Figure 3

Lycogen™ inhibited DSS-induced colonic shorting and bacterial flora. (A) The mice with colitis were orally administered with Lycogen™ (1 mg/kg) for six consecutive days after DSS induction and the colon lengths were determined at day 6 (means ± SD, n = 4). (B) The mice with colitis were orally administered with Lycogen™ (1 mg/kg) for six consecutive days after DSS induction and the amount of bacteria in colon was determined. Significance of differences between groups for continuous variables was assessed using the Student t-test. * p < 0.05.

Figure 4

Therapeutic effect of Lycogen™ in mice with DSS-induced colitis. Mice were orally administered Lycogen™ (1 mg/kg) for six consecutive days after DSS induction. (A) Microscopic features of the colon at day 3 and day 6. Arrows indicate the damaged sites. (B) The microscopic score of DSS-induced colitis (means ± SD, n = 4). Significance of differences between groups for continuous variables was assessed using the Student t-test. * p < 0.05.