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.
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We thank Dr. Sukanya Narasimhan (Yale School of Medicine, New Haven, USA) for carefully editing the manuscript and Dr. Xiaokui Guo (Shanghai Jiao Tong University, Shanghai, China) for providing Leptospira interrogans serovar Lai strain Lai (56601).
This work was supported by the National Natural Science Foundation of China (Nos. 32172872 and 31572582), the Fundamental Research Funds for the Central Universities, China Postdoctoral Science Foundation funded project (2020M670860) and Interdisciplinary Research Funding Program for Doctoral Postgraduates of Jilin University (101832020DJX096).
The authors declare no competing interests.
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Xie, X., Liu, J., Chen, X. et al. Gut microbiota involved in leptospiral infections. ISME J (2021). https://doi.org/10.1038/s41396-021-01122-6