A family of complex cell-surface receptors, some of which
were initially characterized as playing a role in detecting
odors in the nose, has since been found to be involved
in the kidney’s integration of signals from gut microbial
metabolism and the regulation of blood pressure.
These specific cell-surface receptors are members of
a family of proteins known as seven-transmembrane
receptors, so-called because the proteins snake back
and forth across the outer cell membrane seven times,
forming a complex structure that helps the cell sense
and respond to molecules that are outside of the cell.
At least six members of the larger receptor family have
been identified in the kidney, where they appear to
inluence the release of the hormone renin, which helps
to regulate blood pressure by inluencing the amount
of luid excreted by the kidneys. Two members of this
receptor family that are present in the kidney—Olfr78,
which was initially identified in the nose, and Gpr41,
another seven-transmembrane receptor found in other
cell types—are activated in response to short chain
fatty acids produced by bacteria in the gut during
digestion of fats or fiber.
To study the relationship between gut microbial-derived
signals and kidney regulation of blood pressure,
researchers administered the short chain fatty acid
propionate to normal mice; they observed a rapid, but
quickly reversible, drop in blood pressure. In subsequent
studies, mice lacking the Olfr78 gene were observed
to have lower baseline blood pressure than normal
mice, and proprionate further lowered blood pressure
in these mice. However, proprionate administration
raised the blood pressure of mice lacking the Gpr41
gene, suggesting that the Gpr41 protein, when present,
may respond to propionate by lowering blood pressure.
Treatment with antibiotics, which disrupt normal gut
function by killing intestinal bacteria, resulted in a
significant increase in blood pressure in mice lacking
the Olfr78 gene, but had no effect on blood pressure
in normal mice. Together, these results suggest that
the presence of gut microbes producing proprionate
may play a role in the modulation of blood pressure
in mice. This effect appears to be mediated, at least in
part, by Olfr78 and Gpr41, which may work to balance
one another to maintain normal blood pressure as
proprionate levels in the blood luctuate in response to
gut microbial metabolism.
This discovery identifies a heretofore unknown
connection between the gut, kidney, and cardiovascular
systems. This connection may contribute to further
understanding of high blood pressure and the future
development of novel treatments.
Pluznick JL, Protzko RJ, Gevorgyan H, et al. Olfactory
receptor responding to gut microbiota-derived signals plays
a role in renin secretion and blood pressure regulation. Proc
Natl Acad Sci USA 110: 4410-4415, 2013.