Novel Gut Microbiota Modulator, Which Markedly Increases in 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 Muniiciphila 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 also 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 the gut microbiota modulator by significantly increasing A. muciniphila occupancy.

研究背景：肠道菌群参与炎症性肠病（inflammatory bowel disease, IBD）的发病机制，因此抗生素或益生菌或可成为治疗IBD的颇具潜力的方案。嗜黏蛋白阿克曼菌（Akkermansia Muniiciphila）有望成为针对IBD的下一代益生菌，而OPS-2071则是一种新型喹诺酮类药物，对艰难梭菌（Clostridioides difficile）具有强效抗菌活性。
研究目的：本研究旨在评估OPS-2071作为IBD肠道菌群调节剂的潜力。
研究方法：测定了人体肠道菌群中多种细菌的最低抑菌浓度。对正常大鼠每日两次口服给予100mg/kg的OPS-2071后，采用宏基因组分析对粪便中的菌群变化进行分型；同时使用粪便黏蛋白检测试剂盒（Fecal Mucin Assay kit）测定黏蛋白含量。此外，针对饮用含3%硫酸葡聚糖钠的饮用水自由进食10天诱导构建的结肠炎大鼠模型，评估了每日两次给予不同剂量（1、3、10mg/kg）的OPS-2071对粪便症状及粪便菌群的影响。
研究结果：尽管OPS-2071对其他肠道菌株具有较高的抗菌活性，但仅对嗜黏蛋白阿克曼菌（A. muciniphila）展现出极弱的抗菌活性。OPS-2071可快速且显著提升正常大鼠粪便中嗜黏蛋白阿克曼菌的定植占比，同时增加粪便黏蛋白含量。10mg/kg剂量的OPS-2071可显著抑制粪便评分恶化，尤其是血便评分，同时伴随嗜黏蛋白阿克曼菌定植占比的提升。
研究结论：OPS-2071可通过显著提升嗜黏蛋白阿克曼菌的定植占比，作为肠道菌群调节剂成为IBD的新型治疗选择。