Review for 10.1186/s12876-021-01613-y (2021)

Reviewer’s report
Title: 
Short chain fatty acids and colon motility in a mouse model of irritable
bowel syndrome
Version: 
0 
Date: 
20 Jul 2020
Reviewer's report:
The authors used a well established model (acetic acid exposure in neonatal
period) to create a mouse with visceral hypersensitivity. They show that this
model 
has higher amplitude contractions in an isolated colon preparation but less
response to carbacol 
Sodium acetate, sodium propionate and butyric acid induced a dose dependent
decrease of tonic tension, amplitude and frequency of spontaneous in 
the control
group
The effect was reduced in the IBS model particularly so for butyrate. 
Similarly
the effect was less on carbacol induced contraction
The results are clear cut and nicely illustrated and the paper well written though
the discussion seems a bit less well structured.
Specific Comments
1. Abstract: Should mention concentrations of SCFA used
2. Methods: The SCFAs were assessed in faeces but not clear why you did not
choose to measure caecal levels which might be more relevant to the proximal
colon motility which you measured
3. Although you demonstrate hypersensitivity, transit is more relevant to the
microbiota which produce the SCFAs so I think it would have been useful to
assess transit as well. Do we know if it is altered in this model? If so you should
reference this.
4. Results: In control mice the ratio of acetate (0.75±0.07, n=5) propionate
(0.15±0.03, n=5) and butyrate (0.11±0.02, n=5) was 6.5 : 1.3 : 1 (Fig. 5 a). Not
clear in text what units are 
but the figure gives ug/g which is less helpful than
mmol/l as is conventional. Please change in the text.
5. The decrease in 
anaerobic index from control values of -0.352±0.052 ru 
to -
0.437±0.052 ru in the model is fascinating but needs a bit more explanation in
methods 
or introduction to understand why the ratio of C3&C4/C2 is a valid
measure of anaerobicity. The decrease presumably reflects lower acetate values .
Is this related to faster transit?
6. Discussion: Given the contradictory results in the literature I would like to see
a discussion of why this is so. You already mentioned that species differences,
diet and different preparations may all play a role but here it would be useful to
be more specific particularly about your preparation which lacks the input from
enteroendocrine cells and mucosal nerves and is exposed normally to much
lower concentration of SCFAs which are orders of magnitude lower in blood
than the gut lumen. You should discuss how the concentrations you used match
blood levels in mice 
7. You mention the role of ICCs as potential mediators It would have been
helpful to assess these in your model Did you retain any sanples which could be
tested ? It would add a lot to the paper if you could
8. The sentence Incubation of the proximal colon with SCFAs (10
mM)decreased carbachol-induced contractions with a higher potency compared
to butyric acid 
does not make sense . What is being compared with butyrate? 
Minor points
9. Introduction Reference 24 seems wrong Perhaps an error as it refers to a
clinical trial
10. Page 9 line 12 Needs editing 
Mice do not have IBS Please use the term
"mouse 
IBS model" as more accurate.
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