Review for 10.1186/s12876-025-04007-6 (2025)

Title: Impact of Terminal Ileal Microbiota Dysbiosis and Tryptophan Metabolism Alterations
on Mental disorders in Patients with Crohn's Disease
Version: 2 Date: 14 Dec 2024
Reviewer's report:
In this research article, Yin Lin et al. investigate the role of the ileal microbiota in the
production of tryptophan metabolites in Crohn’s disease (CD) patients with and without
psychological comorbidities. The authors found alterations in the mucosal microbiota diversity
and composition in CD patients with depression and anxiety. This microbiota dysbiosis was
associated with an increase in some tryptophan metabolites in these patients. This study is
innovative because investigating the role of ileal microbiota in generating metabolites linked to
pathological conditions is particularly challenging in patients. This study could be considered
for publication in BMC Gastroenterology, but a revision is needed, as mentioned below.
1) The abstract is too long (353 words instead of 350) and has a lot of abbreviations
2) How were the different interleukins, IL-1R, CRP, SAA, Vit B2, Vit B6, Vit A, and Vit D
measured in each patient? This information is missing in the material and method
3) I recommend that the authors place Figure 1, which summarizes the key results, either at the
end of the manuscript (Figure 6) or as a graphical abstract
4) In Figure 2C and 2D, the circos diagrams are unreadable and the different colors used are
not explained in the legend.
5) The reason why the authors were interested in investigating the association between vitamins
and ileal microbiota in relation to psychological disorders in Crohn’s disease patients is not
described (Figure 3C and D).
6) In Figure 3C and 3D, the different correlations between ileal microbiota and clinical factors
in patients with CD were investigated using which control?
7) In Figure 4 and 5, why did the targeted metabolomics analysis on specific tryptophan
metabolites not perform in CRC patients, which were used as a control? The explanation
provided in the discussion is elusive.
8) In Figure 6, why is Mantel's p # 0.05 included? It represents numerous relationships that
obscure the significant results. Panels 6A and 6B are overly complex and could be simplified.
9) The discussion is overly lengthy, making it challenging to follow and obscuring the main
message. I suggest focusing on the most important findings to enhance clarity and impact
10) In Supplement figure 3 and 4. Some results are not significant while stipulated in the title,
“Statistical differences.” Which threshold did you use to assume that a result is significant?
11) Some graphs are blurry, such as Figure 2A (Chao1 and Simpson) and Figure 4A (name of
tryptophan metabolites), and some bacteria names are erased as verrucomicrobiota in Figure 6A.
12) Significant effort is needed to address the grammatical errors in the manuscript, some of
which I have highlighted below. Moreover, there are long sentences line: 76 to 81, 99 to 103,
112 to 116, 470 to 474, which need to be reduced. Some citations are also missing lines 387-388
and lines 459 and 461.
Line 81: research
Line 93: in IBD
Line 105: research on IBD
Line 107: In recent years
Line 123: research
Line 131: proposes
Line 133: mental
Line 318: Serum amyloid A
Line 326: Multivariate
Line 359: Thermi not themi
Line 412: negatively correlated
Line 415: Serum amyloid A
Line 416: negatively associated.
Line 435: was significantly positively
Line 440: robustly
Line 447-448: Prevotella was significantly negatively
Line 484: repeatedly
Line 485: research
Line 508: the feces
Line 527: revealed that
Line 534: tryptophan (without uppercase)
Line 535: play an anti-inflammatory
Line 541: is
Line 556: produces
Line 558: ileal mucosa of CD patients with MD
Line 653: may serve not only as