한빛사논문
Jin Sun You1,2,†, Ji Hyun Yong1,2,†, Gwang Hee Kim1,2, Sungmin Moon2,3, Ki Taek Nam2,3, Ji Hwan Ryu2,3, Mi Young Yoon1,2,4,* and Sang Sun Yoon1,2,4,*
1 Department of Microbiology and Immunology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu Seoul, Seoul 03722, Korea.
2 Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Korea.
3 Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea.
4 Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, Korea.
* Correspondence : Sang Sun Yoon, Mi Young Yoon
†Jin Sun You and Ji Hyun Yong contributed equally to this work.
Abstract
Background
Recent evidence suggests that the commensal microbes act as a barrier against invading pathogens and enteric infections are the consequences of multi-layered interactions among commensals, pathogens, and the host intestinal tissue. However, it remains unclear how perturbations of the gut microbiota compromise host infection resistance, especially through changes at species and metabolite levels.
Results
Here, we illustrate how Bacteroides vulgatus, a dominant species of the Bacteroidetes phylum in mouse intestine, suppresses infection by Vibrio cholerae, an important human pathogen. Clindamycin (CL) is an antibiotic that selectively kills anaerobic bacteria, and accordingly Bacteroidetes are completely eradicated from CL-treated mouse intestines. The Bacteroidetes-depleted adult mice developed severe cholera-like symptoms, when infected with V. cholerae. Germ-free mice mono-associated with B. vulgatus became resistant to V. cholerae infection. Levels of V. cholerae growth-inhibitory metabolites including short-chain fatty acids plummeted upon CL treatment, while levels of compounds that enhance V. cholerae proliferation were elevated. Furthermore, the intestinal colonization process of V. cholerae was well-simulated in CL-treated adult mice.
Conclusions
Overall, we provide insights into how a symbiotic microbe and a pathogenic intruder interact inside host intestine. We identified B. vulgatus as an indigenous microbial species that can suppress intestinal infection. Our results also demonstrate that commensal-derived metabolites are a critical determinant for host resistance against V. cholerae infection, and that CL pretreatment of adult mice generates a simple yet useful model of cholera infection.
Keywords : Vibrio cholerae, Gut microbiota, Colonization resistance, Short-chain fatty acids, Metabolomics, Bacteroides vulgatus, Clindamycin, Amino sugars
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