Beneficial Effects of Fecal Microbiota Transplantation on Ulcerative Colitis in Mice

Abstract

Background: Ulcerative colitis (UC) is a chronic condition and the most common form of inflammatory bowel disease. The goal of standard treatment is mainly to induce and maintain remission with anti-inflammatory, immunosuppressive agents, and/or colectomy. Fecal microbiota transplantation (FMT) has been used successfully to treat relapsing or refractory Clostridium difficile infection. The alteration of microbiota in mouse models of UC as well as in patients suggested the possibility of treating UC with FMT. Aims: To study the effects of FMT on dextran sodium sulfate (DSS)-induced UC model in mice. Methods: Littermates of BALB/c and C57BL/6J were randomized into four groups: normal control , treatment with DSS for 7 days (DSS – FMT), treatment with DSS followed by FMT for another 8 days (DSS + FMT), and treatment with DSS and FMT followed by another 5 days for recovery (remission). Body weight, survival rate, and DAI scores of mice in each group were recorded. Changes in distal colon were studied by histopathology. Alterations of spleen and lamina propria regulatory lymphocytes, major bacterial species in feces and inflammatory cytokines in colon were also studied. Results: C57BL/6J mice experienced more significant weight loss than BALB/c mice after DSS treatment, regardless of whether the two strains of mice were co-housed or not. FMT caused reversal of DAI scores in BALB/c but not in C57BL/6J mice. In BALB/c mice, FMT also reduced colon inflammation that was paralleled by decreased inflammatory cytokine levels, altered bacterial microbiota, and regulatory lymphocyte proportions. Conclusions: FMT is effective in a mouse model of UC through its modulation on gut microbiota and the host immune system.