Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2020; 26(21): 2758-2767
Published online Jun 7, 2020. doi: 10.3748/wjg.v26.i21.2758
Vaccine therapy for dysbiosis-related diseases
Kosuke Fujimoto, Satoshi Uematsu
Kosuke Fujimoto, Satoshi Uematsu, Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
Kosuke Fujimoto, Satoshi Uematsu, Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 113-8654, Japan
Kosuke Fujimoto, Satoshi Uematsu, Division of Metagenome Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo 113-8654, Japan
Satoshi Uematsu, Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo 113-8654, Japan
Author contributions: Fujimoto K and Uematsu S wrote the paper.
Supported by the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Grant-in-Aid for Early-Career Scientists), No. 19K17932 (To Fujimoto K).
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Satoshi Uematsu, MD, PhD, Professor, Department of Immunology and Genomics, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Received: December 27, 2019
Peer-review started: December 27, 2019
First decision: February 14, 2020
Revised: March 27, 2020
Accepted: May 23, 2020
Article in press: May 23, 2020
Published online: June 7, 2020

Progress in genomic analysis has resulted in the proposal that the intestinal microbiota is a crucial environmental factor in the development of multifactorial diseases, such as obesity, diabetes, rheumatoid arthritis, and inflammatory bowel diseases represented by Crohn’s disease and ulcerative colitis. Dysregulated gut microbiome contributes to the pathogenesis of such disorders; however, there are few effective treatments for controlling only disease-mediating bacteria. Here, we review current knowledge about the intestinal microbiome in health and disease, and discuss a regulatory strategy using a parenteral vaccine with emulsified curdlan and CpG oligodeoxynucleotides, which we have recently developed. Unlike other conventional injectable immunizations, our vaccine contributes to the induction of antigen-specific systemic and mucosal immunity. This vaccine strategy can prevent infectious diseases such as Streptococcus pneumoniae infection, and control metabolic symptoms mediated by intestinal bacteria (e.g. Clostridium ramosum) by induction of high titers of antigen-specific IgA at target mucosal sites. In the future, our vaccination approach could be an effective therapy for common infectious diseases and dysbiosis-related disorders that have been difficult to control so far.

Keywords: Dysbiosis, IgA, Microbiome, Mucosal immunity, Pathobiont, Vaccine

Core tip: How to control intestinal pathogenic bacteria that mediate multifactorial diseases is a major concern worldwide. There are few methods for controlling only intestinal pathogenic bacteria; therefore, we have developed a prime–boost type, next-generation mucosal vaccine, and have used it for control of bacterial intestinal diseases. This vaccine can contribute to prevention of Clostridium ramosum-mediated obesity. Thus, this approach might be useful for protecting against microbe-associated disorders of the intestine.