Title: Marked mucosal lipid shifts in treatment refractory inflammatory bowel disease: a
lipidomic study
Version: 0 Date: 10 Jan 2025
Reviewer's report:
The original article by Moe et al. investigates the mucosal lipid composition of CD and UC
patients to disentangle its composition in patients refractory to advanced therapies (anti-TNF
and vedolizumab). The study assesses lipid composition relative to normal controls, patients
prior to therapy initiation, and those achieving successful treatment outcomes. Furthermore, it
investigates potential lipid metabolic pathways underlying observed shifts in lipid composition
using a web-based analytical tool. This study builds on previous findings from the same research
group, providing deeper insights into lipidomic changes in IBD.
Concerns and suggestions:
1. Sample Size and Statistical Power:
o The study lacks a detailed discussion of power calculations or a clear rationale for the chosen
sample size. Why did the patients included in the study have biopsies available for lipidomic
analysis and the other from the same cohort did not? Addressing this would enhance the
robustness of the conclusions.
2. Patients naïve to advanced therapy:
o Are these patients different from the ones exposed to advanced therapy?
3. Definition of Deep Remission:
o The definition name of deep remission used in the study is somewhat misleading. A more
comprehensive definition, such as combined remission (mucosal healing and clinical remission),
would be preferable.
4. Definition of Moderate to Severe Inflammation:
o Clarification on whether inflammation severity is defined by clinical or endoscopic disease
activity is needed.
5. SES-CD Scoring in CD Non-Responders:
o It is unclear how the SES-CD score interquartile range (IQR) in the CD non-response group
begins at 3…
6. Focus on Anti-TNF Therapy:
o With only two patients refractory to vedolizumab included, the analysis lacks sufficient power
to draw meaningful conclusions about this subgroup. Limiting the study to anti-TNF-refractory
patients could improve internal and external validity, facilitating future comparisons with other
studies and mechanisms of action. This recommendation is especially pertinent given the study’s
remission definition, which includes TNF levels.
7. Biopsy Location:
o Including the location of biopsies in the results section would provide a critical context for
interpreting lipidomic findings.
8. Disease Location Analysis:
o Performing subanalyses based on disease location (ileum versus colon) in CD would offer
valuable insights into localized lipidomic differences and strengthen the study's conclusions.
9. Table 1:
o Statistical analysis results for group comparisons should be included in Table 1
10. Discussion:
o The discussion could benefit from comparing the study’s mucosal lipidomic data with findings
from fecal lipidomic profiles. This would help contextualize the results within the broader
lipidomics landscape.
o “The data regarding diet were incomplete, but seemed quite similar between the groups” please
provide data on this statement
o “making the connections between lipid profiles and immunological response more valuable”
besides TNF level no other connection has been provided here
Title: Marked mucosal lipid shifts in treatment refractory inflammatory bowel disease: a
lipidomic study
Version: 0 Date: 10 Jan 2025
Reviewer's report:
The original article by Moe et al. investigates the mucosal lipid composition of CD and UC
patients to disentangle its composition in patients refractory to advanced therapies (anti-TNF
and vedolizumab). The study assesses lipid composition relative to normal controls, patients
prior to therapy initiation, and those achieving successful treatment outcomes. Furthermore, it
investigates potential lipid metabolic pathways underlying observed shifts in lipid composition
using a web-based analytical tool. This study builds on previous findings from the same research
group, providing deeper insights into lipidomic changes in IBD.
Concerns and suggestions:
1. Sample Size and Statistical Power:
o The study lacks a detailed discussion of power calculations or a clear rationale for the chosen
sample size. Why did the patients included in the study have biopsies available for lipidomic
analysis and the other from the same cohort did not? Addressing this would enhance the
robustness of the conclusions.
2. Patients naïve to advanced therapy:
o Are these patients different from the ones exposed to advanced therapy?
3. Definition of Deep Remission:
o The definition name of deep remission used in the study is somewhat misleading. A more
comprehensive definition, such as combined remission (mucosal healing and clinical remission),
would be preferable.
4. Definition of Moderate to Severe Inflammation:
o Clarification on whether inflammation severity is defined by clinical or endoscopic disease
activity is needed.
5. SES-CD Scoring in CD Non-Responders:
o It is unclear how the SES-CD score interquartile range (IQR) in the CD non-response group
begins at 3…
6. Focus on Anti-TNF Therapy:
o With only two patients refractory to vedolizumab included, the analysis lacks sufficient power
to draw meaningful conclusions about this subgroup. Limiting the study to anti-TNF-refractory
patients could improve internal and external validity, facilitating future comparisons with other
studies and mechanisms of action. This recommendation is especially pertinent given the study’s
remission definition, which includes TNF levels.
7. Biopsy Location:
o Including the location of biopsies in the results section would provide a critical context for
interpreting lipidomic findings.
8. Disease Location Analysis:
o Performing subanalyses based on disease location (ileum versus colon) in CD would offer
valuable insights into localized lipidomic differences and strengthen the study's conclusions.
9. Table 1:
o Statistical analysis results for group comparisons should be included in Table 1
10. Discussion:
o The discussion could benefit from comparing the study’s mucosal lipidomic data with findings
from fecal lipidomic profiles. This would help contextualize the results within the broader
lipidomics landscape.
o “The data regarding diet were incomplete, but seemed quite similar between the groups” please
provide data on this statement
o “making the connections between lipid profiles and immunological response more valuable”
besides TNF level no other connection has been provided here
Please review this paper.
user
Title: Marked mucosal lipid shifts in treatment refractory inflammatory bowel disease: a
lipidomic study
Version: 0 Date: 10 Jan 2025
Reviewer's report:
The original article by Moe et al. investigates the mucosal lipid composition of CD and UC
patients to disentangle its composition in patients refractory to advanced therapies (anti-TNF
and vedolizumab). The study assesses lipid composition relative to normal controls, patients
prior to therapy initiation, and those achieving successful treatment outcomes. Furthermore, it
investigates potential lipid metabolic pathways underlying observed shifts in lipid composition
using a web-based analytical tool. This study builds on previous findings from the same research
group, providing deeper insights into lipidomic changes in IBD.
Concerns and suggestions:
1. Sample Size and Statistical Power:
o The study lacks a detailed discussion of power calculations or a clear rationale for the chosen
sample size. Why did the patients included in the study have biopsies available for lipidomic
analysis and the other from the same cohort did not? Addressing this would enhance the
robustness of the conclusions.
2. Patients naïve to advanced therapy:
o Are these patients different from the ones exposed to advanced therapy?
3. Definition of Deep Remission:
o The definition name of deep remission used in the study is somewhat misleading. A more
comprehensive definition, such as combined remission (mucosal healing and clinical remission),
would be preferable.
4. Definition of Moderate to Severe Inflammation:
o Clarification on whether inflammation severity is defined by clinical or endoscopic disease
activity is needed.
5. SES-CD Scoring in CD Non-Responders:
o It is unclear how the SES-CD score interquartile range (IQR) in the CD non-response group
begins at 3…
6. Focus on Anti-TNF Therapy:
o With only two patients refractory to vedolizumab included, the analysis lacks sufficient power
to draw meaningful conclusions about this subgroup. Limiting the study to anti-TNF-refractory
patients could improve internal and external validity, facilitating future comparisons with other
studies and mechanisms of action. This recommendation is especially pertinent given the study’s
remission definition, which includes TNF levels.
7. Biopsy Location:
o Including the location of biopsies in the results section would provide a critical context for
interpreting lipidomic findings.
8. Disease Location Analysis:
o Performing subanalyses based on disease location (ileum versus colon) in CD would offer
valuable insights into localized lipidomic differences and strengthen the study's conclusions.
9. Table 1:
o Statistical analysis results for group comparisons should be included in Table 1
10. Discussion:
o The discussion could benefit from comparing the study’s mucosal lipidomic data with findings
from fecal lipidomic profiles. This would help contextualize the results within the broader
lipidomics landscape.
o “The data regarding diet were incomplete, but seemed quite similar between the groups” please
provide data on this statement
o “making the connections between lipid profiles and immunological response more valuable”
besides TNF level no other connection has been provided here
assistant