Prolonged Gut Dysbiosis and Fecal Excretion of Hepatitis A Virus in Patients Infected with Human Immunodeficiency Virus
Aya Ishizaka,
Michiko Koga,
Taketoshi Mizutani,
Lay Ahyoung Lim,
Eisuke Adachi,
Kazuhiko Ikeuchi,
Ryuta Ueda,
Haruyo Aoyagi,
Satoshi Tanaka,
Hiroshi Kiyono,
Tetsuro Matano,
Hideki Aizaki,
Sachiyo Yoshio,
Eiji Mita,
Masamichi Muramatsu,
Tatsuya Kanto,
Takeya Tsutsumi,
Hiroshi Yotsuyanagi
Affiliations
Aya Ishizaka
Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Michiko Koga
Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Taketoshi Mizutani
Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Lay Ahyoung Lim
Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Eisuke Adachi
Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Kazuhiko Ikeuchi
Department of Infectious Diseases and Applied Immunology, IMSUT Hospital of Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Ryuta Ueda
Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Haruyo Aoyagi
Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Satoshi Tanaka
Department of Gastroenterology and Hepatology, National Hospital Organization Osaka National Hospital, Osaka 540-0006, Japan
Hiroshi Kiyono
International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Tetsuro Matano
AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Hideki Aizaki
Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Sachiyo Yoshio
The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba 272-8516, Japan
Eiji Mita
Department of Gastroenterology and Hepatology, National Hospital Organization Osaka National Hospital, Osaka 540-0006, Japan
Masamichi Muramatsu
Department of Virology II, National Institute of Infectious Diseases, Tokyo 162-8640, Japan
Tatsuya Kanto
The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba 272-8516, Japan
Takeya Tsutsumi
Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Hiroshi Yotsuyanagi
Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan
Hepatitis A virus (HAV) causes transient acute infection, and little is known of viral shedding via the duodenum and into the intestinal environment, including the gut microbiome, from the period of infection until after the recovery of symptoms. Therefore, in this study, we aimed to comprehensively observe the amount of virus excreted into the intestinal tract, the changes in the intestinal microbiome, and the level of inflammation during the healing process. We used blood and stool specimens from patients with human immunodeficiency virus who were infected with HAV during the HAV outbreak in Japan in 2018. Moreover, we observed changes in fecal HAV RNA and quantified the plasma cytokine level and gut microbiome by 16S rRNA analysis from clinical onset to at least 6 months after healing. HAV was detected from clinical onset up to a period of more than 150 days. Immediately after infection, many pro-inflammatory cytokines were elicited, and some cytokines showed different behaviors. The intestinal microbiome changed significantly after infection (dysbiosis), and the dysbiosis continued for a long time after healing. These observations suggest that the immunocompromised state is associated with prolonged viral shedding into the intestinal tract and delayed recovery of the intestinal environment.
