Mast cells are mainly located at the front line of surface barriers, such as the skin and gut mucosa. Mucosal mast cells are important for the clearance/elimination of parasites and pathogens via the release of chondroitin sulfate and proteases. These mediators are also involved in the pathogenesis of allergy and inflammatory symptoms. The main activator of mast cells, IgE, was discovered about 50 years ago; however, recent evidence has revealed the importance of IgE-independent activation pathways involved in the aggravation of allergy and inflammation. Based on past findings that mast cells are activated in the intestinal mucosa of patients with Crohn’s disease, we screened out the activator of mast cells in intestinal inflammation and found that extracellular adenosine tri-phosphate (ATP) was involved. Extracellular ATP is released from damaged cells, but some species of commensal bacteria also actively release ATP into the extracellular space, and require it for “commensal mutualism”. Intriguingly, the response to extracellular ATP was limited in skin mast cells. This phenotype was considered to be a tissue-specific regulation of mast cell function, which was mediated by mesenchymal cells. The disruption of skin-specific regulation of mast cells causes chronic inflammation in the skin and depends on skin commensal bacterial stimulation. Taken together, the maintenance of surface barriers in the body is tightly regulated by immune-mesenchymal interactions. It is expected that the development of novel therapeutic approaches for chronic inflammation, which can be considered as a disruption of “symbiosis and elimination” mechanisms, will be used to target errors of tissue-specific immune (e.g. mast cells) responses and mesenchymal cell interactions.

Intestinal tissues are continuously exposed to numerous numbers and kinds of bacteria, which affect the intestinal immune system of the host. This interaction allows the maintenance of homeostasis in the intestine. Recent advances in omics analyses have revealed that an inappropriate balance of intestinal bacteria leads to the development of various diseases such as gastrointestinal and cardiovascular diseases. In addition to intestinal bacteria, dietary materials are known to regulate immune functions directly and indirectly through interaction with intestinal bacteria; therefore, it is necessary to consider the triangular network of “diets-intestinal bacteria-intestinal immunity” for the regulation of health and diseases. In this review, we focus on lipids (or oils) and describe recent findings regarding immune regulation through lipid metabolites and intestinal bacteria.

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.