Vaccine therapy for dysbiosis-related diseases

Abstract

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.