The Importance of Genetic Research into the Most Dominant Species of Human Intestinal Indigenous Microbiota

Abstract

Gut microbiota have been extensively analyzed, and of late, control of the intestinal environment is garnering increasing interest. The results of a comparison of the changes in gut microbiota and transcriptomes due to a change in diet suggest that control of the gene function of intestinal bacteria is vital for the control of the intestinal environment. However, only the functions of a few genes are predictable using the nucleotide sequences obtained from the metagenomic data of human gut microbiota, Therefore, control of gut bacterial gene function is difficult at present. Experimental identification of the functions of intestinal bacterial genes is imperative to overcome this situation. Intestinal microbial cells are inhibited by the immune system of the large intestine and only a small number are in contact with human intestinal epithelial tissue. In contrast, the metabolites of intestinal bacteria can pass through the intestinal epithelium, and are absorbed by the body, and have a more direct effect on human health. In order to control the metabolic products of intestinal bacteria, it is essential to control the gene functions related to their synthesis and transport. We established a high-throughput cultivation system of the most dominant species of indigenous human intestinal microbiota, with the goal of controlling the gut environment through the elucidation of the gene functions of intestinal bacteria. Using this system we analyzed the synthesis and transport of polyamine by intestinal bacteria. These results were compared with those obtained by in silico analysis, and the results suggest the existence of a novel polyamine synthase and transport proteins. Next, an analysis was conducted using strains with gene deletions and complementation for the polyamine synthetic system of the genus Bacteroides. As intestinal bacteria form complex microbiota, it is thought that metabolites are exchanged among the bacteria constituting the microbiota. We co-cultured genetically engineered Escherichia coli and Enterococcus faecalis and demonstrated the presence of a polyamine synthetic pathway spanning multiple bacterial species. We also outline the trend of domestic and international research using genetically engineered intestinal bacteria and the ripple effects of studies in which intestinal bacteria have been analyzed genetically. Many studies of intestinal bacteria have focused mainly on the hosts. However, our study of intestinal bacteria emphasizes the analysis of gut bacteria, the understanding of which will lead to future control of the intestinal environment. Studies of intestinal bacteria at the gene level are indispensable for a better understanding of their control; therefore, the importance of this research will progressively increase in the future.