Review for 10.1186/s12876-022-02513-5 (2022)

Title: Expression of 5-hydroxytryptamine 7 receptor in intestinal mucosa correlates with the
degree of intestinal inflammation in Crohn's disease
Version: 1 Date: 28 Mar 2022
Reviewer's report:
The authors have assessed the correlation between intestinal 5-HT7R expression and disease
activity in Crohn's disease. Previous research has shown that 5-HT7R is increased in active
Crohn's disease lesions, however, the novelty of the current manuscript is the assessment of
correlation with clinical, radiological, and endoscopic activity scores.
I would suggest the following revisions to the current manuscript.
MAJOR
1. Title
The authors have indeed showed a correlation between disease activity and 5-HT7R expression
levels, however, the results do not fully support the claim that 5-HT7R "predicts" intestinal
inflammation. Therefore, I would suggest adapting the title accordingly.
2. Material and methods
- A more detailed description of the study design is required. No information is available on in-,
and exclusion criteria nor on study flow (number of patients screened, reasons for exclusion,..).
- Was a qualitative PCR or quantitative PCR performed and which software was used for analysis
of the expression levels?
- Why was "remission" based solely on clinical scores and not more objective markers of
remission such as biochemical or endoscopic data?
3. Discussion
The authors should add a strengths and limitations section to the discussion of this manuscript.
MINOR
There are still some grammatical/typographical errors in the manuscript.
1. Materials and methods
- No information is available on which samples were exactly used for immunohistochemistry
and which for PCR. Was (q)PCR only performed on regions with active inflammation or on
all biopsies?
- Statistical methods: from the methods and results it is not clear if the correlation is always
assessed with the Spearman test or also with a linear (Pearson) correlation coefficient.
2. Results
- I would suggest the authors start the results section with the description of baseline
characteristics. I would also suggest to show the baseline characteristics in Table 1 for the 3
groups separately (active Crohn, Crohn in remission, controls).
- If possible I would optimize Figure 2 since the contrast between the staining/black background
is not optimal.
- It is not clear if the global MaRIA score was used or if the MaRIA score of the affected segment
was correlated with the 5-HT7R expression of that same segment.
- If available I would suggest also correlating 5-HT7R levels with fecal calprotectine levels.
- Section 3.5: The correlation between the 5-HT7R expression levels and CRP, WBC, ESR could
be further supported with the p-values.
- Figure 5D shows the MaRIA score and not endoscopy.
3. Discussion
- "Our study demonstrated that the 5-HT7R positive cells were mainly located in both the
neuronal intermuscular plexus and submucosal plexus, especially in the annular muscularis and
intermuscular plexus". More data supporting this statement should be added to the results.
- "It was demonstrated that the expression of 5-HT7R aggravated the process of enteritis, while
the activation of the receptor promoted the anti-inflammatory response. ". In my opinion the
authors have insufficient data in the results to support this statement.
- "On the other hand, 5-HT7R expression level could be used to assess the severity of CD so it
might help to avoid the risks associated with endoscopy." The current study assessed 5-HT7R
expression in intestinal biopsies obtained with endoscopy. Can the authors address how this
could be assessed in the future without endoscopy?