Though I am a
little bit tired reviewing papers about gut microbiome, this new
paper in Cell is so cute I could not ignore it.
GI tract's proper motility
is obviously very important for a good health. It is also quite
obvious that food and gut neuronal network regulate GI tract motility
and of course, gut muscles. Now this gut muscles are specialized type
of muscles called smooth muscles.
This short and very
simple paper published in Cell (1) has made very unusual observation.
One of the senior authors on this paper is Miriam Merad. She is well
known for her work on macrophages.
First, the authors found
that gut outer muscular layer harbored Cx3CR1+ macrophages. The
development of these muscle associated-macrophages was dependent on
CSF-1 (M-CSF) receptor as shown by their absence in CSF receptor-1 or CSF-1 KO mice.
In
addition, intra-peritoneal injection of anti-CSF1 antibody
preferentially depleted muscle-associated macrophages.
The parallel set of
experiments showed that ex vivo gut motility (peristaltic
movements) were modified (accelerated) by anti-CSF1 antibody mediated
muscle-associated macrophages depletion.
This was a peculiar
observation since this muscle macrophages are sitting deep in the
outer muscles layer of the gut and do no directly interact with gut
flora, for example.
So, how their depletion
affected GI tract motility?
To find the answer, the
authors run microarray analysis on purified muscle-associated
macrophages and found that molecule, called BMP2, was highly
expressed by these macrophages.
On the other hand, macrophages
depletion affected neurons located in close proximity to the muscle
macrophages. These neurons were found to express receptor for BMP2
and to express CSF-1.
It is well described
that germ-free mice have GI tract motility issues. Anyone who worked
with mice and seen germ-free mice intestine can ascertain that their
colon is of enormous size. To further understand the relationship
between neurons and macrophages and gut flora, the authors conducted
series of experiments with antibiotic-treated mice. Antibiotic
treatment diminished BMP2 expression in muscle macrophages and
reduced GI peristaltic movement that was reversible with the addition
of LPS in drinking water. Interestingly in vitro gut neurons
produce more of CSF-1 in response to LPS.
In summary, the authors
proposed the following model of physiological gut motility: products
of gut microbiota induce neuronal cells (or other cells) in the gut
to secrete CSF-1. CSF-1 stimulates development and/or maintenance of
muscle-associated macrophages, which in turn secrete BMP2 required
for normal gut neuronal activity.
This study represents
another example supporting growing evidence that macrophages play more
fundamental role in physiology, including already described role in thermoregulation.
David
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