Leptospirosis is a re-emerging zoonotic disease worldwide. Intestinal bleeding is a common but neglected symptom in severe leptospirosis. The regulatory mechanism of the gut microbiota on leptospirosis is still unclear. In this study, we found that Leptospira interrogans infection changed the composition of the gut microbiota in mice. Weight loss and an increased leptospiral load in organs were observed in the gut microbiota-depleted mice compared with those in the control mice. Moreover, fecal microbiota transplantation (FMT) to the microbiota-depleted mice reversed these effects. The phagocytosis response and inflammatory response in bone marrow-derived macrophages and thioglycolate-induced peritoneal macrophages were diminished in the microbiota-depleted mice after infection. However, the phagocytosis response and inflammatory response in resident peritoneal macrophage were not affected in the microbiota-depleted mice after infection. The diminished macrophage disappearance reaction (bacterial entry into the peritoneum acutely induced macrophage adherence to form local clots and out of the fluid phase) led to an increased leptospiral load in the peritoneal cavity in the microbiota-depleted mice. In addition, the impaired capacity of macrophages to clear leptospires increased leptospiral dissemination in Leptospira-infected microbiota-depleted mice. Our study identified the microbiota as an endogenous defense against L. interrogans infection. Modulating the structure and function of the gut microbiota may provide new individualized preventative strategies for the control of leptospirosis and related spirochetal infections.

钩端螺旋体病是一种在世界范围内重新出现的人畜共患疾病。肠道出血是严重钩端螺旋体病常见但被忽视的症状。肠道菌群对钩端螺旋体病的调控机制尚不清楚。在本研究中，我们发现问号钩端螺旋体感染改变了小鼠肠道菌群的组成。与对照小鼠相比，在肠道微生物群耗尽的小鼠中观察到体重减轻和器官中的钩端螺旋体负荷增加。此外，粪便微生物群移植 (FMT) 到微生物群耗尽的小鼠可以逆转这些影响。在感染后微生物群耗尽的小鼠中，骨髓来源的巨噬细胞和巯基乙酸盐诱导的腹膜巨噬细胞的吞噬反应和炎症反应减弱。然而，在感染后微生物群耗尽的小鼠中，驻留腹膜巨噬细胞的吞噬反应和炎症反应没有受到影响。减少的巨噬细胞消失反应（细菌进入腹膜急性诱导巨噬细胞粘附形成局部凝块并离开液相）导致微生物群耗尽小鼠腹膜腔中的钩端螺旋体负荷增加。此外，巨噬细胞清除钩端螺旋体的能力受损增加了钩端螺旋体在钩端螺旋体感染的微生物群耗尽小鼠。我们的研究确定微生物群是对抗问号乳杆菌感染的内源性防御。调节肠道微生物群的结构和功能可能为控制钩端螺旋体病和相关螺旋体感染提供新的个体化预防策略。