Takako Nakashima1, Kazuyuki Fujii2, Toyokazu Seki3, Masashi Aoyama2, Atsushi Azuma2, Hideki Kawasome2. 1. New Drug Research Division, Department of Medical Innovations, Otsuka Pharmaceutical Co., Ltd, 463-10, Kagasuno, Kawauchi-cho, Tokushima-shi, Tokushima, 771-0192, Japan. Nakashima.Takako@otsuka.jp. 2. New Drug Research Division, Department of Medical Innovations, Otsuka Pharmaceutical Co., Ltd, 463-10, Kagasuno, Kawauchi-cho, Tokushima-shi, Tokushima, 771-0192, Japan. 3. New Drug Research Division, Department of Lead Discovery Research, Otsuka Pharmaceutical Co., Ltd, 463-10, Kagasuno, Kawauchi-cho, Tokushima-shi, Tokushima, 771-0192, Japan.
Abstract
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.
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.
Authors: Nicholas A Lesniak; Sarah Tomkovich; Andrew Henry; Ana Taylor; Joanna Colovas; Lucas Bishop; Kathryn McBride; Patrick D Schloss Journal: mBio Date: 2022-08-01 Impact factor: 7.786
Authors: Nicholas A Lesniak; Alyxandria M Schubert; Kaitlin J Flynn; Jhansi L Leslie; Hamide Sinani; Ingrid L Bergin; Vincent B Young; Patrick D Schloss Journal: mBio Date: 2022-07-20 Impact factor: 7.786