Scientists at the University of Tokyo have discovered that specific gut-dwelling bacteria control key immune cells that combat allergies and autoimmune diseases. The paper describing these findings was published in today's issue of the journal Science, and technology originating from the work is being advanced by start-up Vedanta Biosciences.
Dr. Kenya Honda and colleagues initially showed that mice raised in sterile conditions had deficient levels of regulatory T cells in their colon compared to mice colonized with microbes. "Regulatory T cells are the peace-keepers of the immune system," says Dr. Alexander Rudensky, tri-institutional professor at the Memorial Sloan-Kettering Institute, the Rockefeller University, and Cornell University, whose previous work helped describe this specialized subset of T cells. "When these cells are missing, the body has trouble putting the brakes on excessive immune responses."
The team of researchers led by Honda then zeroed in on a subset of gut microbes belonging to the Clostridia class that were responsible for triggering production of regulatory T cells. Feeding these "Good Clostridia" to mice prevented the development of allergies and inflammatory bowel disease. "For millions of years, we have co-evolved with our gut microbes, communicating in an ancient language that may hold critical clues about how autoimmune and infectious diseases develop," says Dr. Ruslan Medzhitov, professor of immunobiology at Yale, who authored pioneering studies of the innate immune system. "Researchers like Dr. Honda are making important strides to begin decoding this complex language."
This newly understood beneficial role of certain species of Clostridia may be reminiscent of the opposite effects on health of "good" and "bad" cholesterol. While some species are harmful pathogens, such as C. difficile, many other Clostridia species are harmless or even beneficial as illustrated by Honda's work. "These surprising findings suggest we should revisit how we view this class of microbes," says Dr. Dan Littman, professor of molecular immunology at NYU, whose previous work shed light on the development of Th17 cells in response to microbial signals. Littman added that Honda's findings "open up new treatment options for preventing and treating a number of immune-related disorders."
Honda's paper is the latest of a series of recent high profile publications that have followed the launch of the Human Microbiome Project by the NIH, and of similar international efforts aimed at exploring the roles of the human microbiome in health and disease. "The human microbiome is an exciting area of research that may enable a completely new class of therapies," says Dr. Ben Shapiro, chairman and senior partner of PureTech Ventures and former executive vice president of worldwide basic and external research at Merck. "PureTech has made a significant commitment to translating research related to the microbiome, and we have a number of exciting technologies and programs under development."