Dr. Kenya Honda of the School of Medicine, Keio University, Japan, spoke at the Keystone Symposium in March, 2015. After his presentation, called Regulation of T Cells by the Gut Microbiota, he spoke with GMFH editors about his work.
What is your current understanding of how T helper type 17 (Th17) cells are induced in the gut?
Th17 cells are most abundantly present in the gut, [with]in our body. They are affected by the presence of the gut microbiota. In mice, one species of bacteria named segmented filamentous bacteria is the [best] inducer of Th17 cells. Segmented filamentous bacteria colonize in the small intestine, and in the small intestine they adhere to the small intestinal epithelial surfaces and induce Th17 cells.
Actually, Th17 cells are most abundantly present in the small intestine, particularly the terminal ileum, because of the presence of the adhering segmented filamentous bacteria. The mechanism, we don’t know yet, but the adhesion by segmented filamentous bacteria is a key factor for the Th17 [cells]. We don’t know the details of molecular mechanisms underlying adhesion-mediated Th17 induction.
When it comes to the immune system, how are the oral bacteria related to the gut bacteria?
That [is] still a very active field, so [it’s] not well-known how oral bacteria connect to gut bacteria and how oral bacteria affect [the] systemic or gut immune system.
We actually examined the oral bacteria — I mean saliva samples — and how they affect the gut immune system. Because you actually swallow 1 litre or 1.5 litre[s] of saliva every single day. You can imagine how substantial that amount is.
Among the saliva microbiota, some species seemed to act on the gut immune system when innoculated into germ-free mice. Some can colonize in the gut, and expand and affect the gut immune system. We identified some specific bacterial species, usually colonizing in the oral cavity, but when gavaged into germ-free mice, they colonized in the gut and affect[ed] the gut immune system.
Do you think viruses or fungi are important in the relationship between gut microbiota and the host immune system?
[In our lab] we put that aside, the presence of the viruses or fungi in the gut or oral cavity. But Skip Virgin’s talk, based on his research, [showed that] the viruses permanently affect gut microbiota composition and also the phenotype of the host. So we need to examine the effect of the presence of the colonic infecting viruses or fungi and the relationship [of] these viruses or fungi with bacteria, and how these kingdoms affect host physiology.
For more on Honda’s work (i.e. how microbes foster Tregs & how this might be used therapeutically), see this National Geographic blog post by Carl Zimmer.
For more on the recent Keystone Symposium, search for the hashtag #KSgut on Twitter.