Novel Gut Microbiota Modulator, Which Markedly Increases Akkermansia muciniphila Occupancy, Ameliorates Experimental Colitis in Rats

Background Since gut microbiota is involved in the pathogenesis of inflammatory bowel disease (IBD), antibiotics or probiotics may be attractive options for the treatment of IBD. Akkermansia muciniphila is expected as a next-generation probiotic for IBD, and OPS-2071 is a novel quinolone with potent antibacterial activity against Clostridioides difficile. Aims The aim of this study is to assess the potential of OPS-2071 as a gut microbiota modulator for IBD. Methods Minimum inhibitory concentrations of several bacteria in the human intestinal microbiota were determined. Microbiota changes in the feces were typed using metagenomic analysis after oral administration of OPS-2071 (100 mg/kg) twice a day to normal rats. The amounts of mucin were determined using the Fecal Mucin Assay Kit. The effects of OPS-2071 (1, 3, 10 mg/kg) twice a day on fecal symptoms and fecal microbiota were evaluated in a colitis rat model induced by free access to drinking water containing 3% dextran sulfate sodium for 10 days. Results OPS-2071 showed notably low antibacterial activity against only A. muciniphila in spite of higher antimicrobial activity against other strains of intestinal bacteria. OPS-2071 rapidly and dramatically increased the occupancy of A. muciniphila as well as the amount of mucin in the feces of normal rats. OPS-2071 (10 mg/kg) significantly suppressed the exacerbation of stool scores, especially the bloody stool score, with the increase in A. muciniphila occupancy. Conclusions OPS-2071 is expected to be a new therapeutic option for IBD as a gut microbiota modulator by significantly increasing A. muciniphila occupancy.