Physiology PI Maya Kaelberer publishes new paper in 'Nature'!
A gut sense for gut sensing
Model for microbial pattern sensing by neuroepithelial circuits to drive behavioural change. Bacterial flagellin is detected by TLR5 in colonic PYY-labelled cells, which in turn release PYY to activate vagal neurons through Y2R. Activation of this circuit contributes to overall food intake.
Physiology PI Maya Kaelberer, PhD, is a co-corresponding author on a paper just published in Nature.
Abstract
To coexist with its resident microorganisms, the host must have a sense to adjust its behaviour in response to them. In the intestine, a sense for nutrients transduced to the brain through neuroepithelial circuits guides appetitive choices1-5. However, a sense that allows the host to respond in real time to stimuli arising from resident gut microorganisms remains to be uncovered. Here we show that in the mouse colon, the ubiquitous microbial pattern flagellin-a unifying feature across phyla6-stimulates Toll-like receptor 5 (TLR5) in peptide YY (PYY)-labelled colonic neuropod cells. This stimulation leads to PYY release onto NPY2R vagal nodose neurons to regulate feeding. Mice lacking TLR5 in these cells eat more and gain more weight than controls. We found that flagellin does not act on the nerve directly. Instead, flagellin stimulates neuropod cells from the colonic lumen to reduce feeding through a gut-brain sensory neural circuit. Moreover, flagellin reduces feeding independent of immune responses, metabolic changes or the presence of gut microbiota. This sense enables the host to adjust its behaviour in response to a molecular pattern from its resident microorganisms. We call this sense at the interface of the biota and the brain the neurobiotic sense7.
The paper, "A gut sense for a microbial pattern regulates feeding", can be found on Nature.