The effects of fecal microbiota transplantation administered with oral or rectal route in colitis model of rat

Objective: It was aimed to evaluate the effects of fecal microbiota transplantation (FMT) administered in two different ways, oral or rectal, in the rat ulcerative colitis model induced by acetic acid. Material and Methods: In the study, 2.5-3-month-old 52 female Wistar rats were used. 44 rats randomly separated into 6 groups: Ulcerative Colitis (UC) (n=8), UC+Oral FMT (n=8), UC+Rectal FMT (n=8), Control+Oral FMT (n=7), Control+Rectal FMT (n=7) and Control (n=6). The remaining 8 healthy rats were used as fecal donors. For colitis induction, 1 ml of 4% acetic acid was administered intrarectally. One day after colitis induction, FMT was administered orally or rectally 3 times in total to the control and experimental groups, every other day (on days 1, 3 and 5). One day after the last FMT administration, rats were euthanized, and feces and colon tissue samples were collected. Colon weight and length, tissue myeloperoxidase (MPO), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) levels, and fecal butyrate level were determined. Colon tissue was evaluated macroscopically and microscopically. Data were evaluated with one-way analysis of variance (ANOVA) or Kruskal Wallis test according to normal distribution. Differences between groups were determined with the Duncan or Mann Whitney U tests. Results: While colitis induction caused a decrease in body weight compared to the initial values (p<0,01), body weight returned to normal values in the colitis groups that received FMT. Colitis increased colon weight and colon weight/colon length ratio, but no significant increase was observed in the FMT-treated groups (p<0,001). In colon macroscopic evaluation, colitis severity was significantly higher in the colitis group than in the control groups (p<0,001). In the colitis groups that received FMT, it was determined that the severity of colitis was not statistically different from the control groups and was less than the colitis group, although not significantly. While necrosis depth, necrosis width and fibrosis increased in the colitis group compared to the control groups (p<0,01), no significant increase was detected in the FMT-treated groups. Although the severity and width of inflammation decreased in the FMT-treated colitis groups, the inflammation was significantly higher in all colitis groups compared to the control group (p<0,01). While colitis induction increased TNF-α and IL-1β levels (p<0,01), orally and rectally administered FMT reduced the increase of these. While MPO levels increased in the colitis and colitis received rectal FMT group compared to the control oral FMT group, the increase in the rectal FMT colitis group was also found to be significant compared to the control and colitis received oral FMT group (p<0,05). On the other hand, IL-10 concentration in the rectal FMT treated colitis group increased compared to the colitis group (p<0,05). It was determined that the fecal butyrate level was higher in the colitis group and FMT administered control group than in other groups (p<0,001). Conclusion: FMT improved the tissue damage and inflammatory cytokine increase caused by colitis. It was observed that there was no significant difference in the treatment effectiveness of FMT between oral or rectal administration in terms of colon weight, macroscopic and microscopic scores and inflammatory cytokines. It can be stated that FMT applied rectally in the treatment of colitis is superior in terms of increasing the anti-inflammatory cytokine IL-10, and microscopic improvement, although no statistical significance was detected in the scoring. Keywords: Butyrate, Fecal Microbiota Transplantation, Immunity, Rat, Ulcerative Colitis