Methods to Prevent or Treat Refractory Diseases by Focusing on Intestinal Microbes Using LPS and Macrophages

Intestinal microbes are known to influence host homeostasis by producing various substances. Recently, the presence of a diverse range of intestinal microbiota has been shown to play a key role in the maintenance of health, along with influencing the host's innate immunity towards various diseases. For example, fecal microbiota transplantation (FMT) from healthy individuals was remarkably effective in cases of refractory Clostridium difficile colitis. Conversely, decreased number of intestinal microbes resulting from the oral administration of antibiotics reportedly suppressed the antitumor effects of immunotherapy or anticancer drugs. Furthermore, it has been shown that a change in the intestinal environment triggered by oral administration of antibiotics resulted in increased number of drug-resistant microbes causing nosocomial infections. Intestinal microbes are also shown to be effective in cancer treatment as they activate macrophages at the site of cancer. One of the effects of intestinal microbes on hosts that has been gaining increasing attention is the biological regulation caused by the lipopolysaccharides (LPS) produced by Gram-negative bacteria. Among the intestinal microbiota present in the host, Gram-negative bacteria form the most dominant flora. The administration of antibiotics leads to a decreased number of intestinal microbes, as well as to suppression of cancer immunotherapy effects or anticancer drug effects, and this deterioration has been shown to be improved by oral administration of LPS. In this article, we discuss the functions of intestinal microbiota, that is currently undergoing a paradigm shift in relation to maintenance of health and the validity of LPS as a possible target for bio-treatment in the future.