Review for 10.1186/s12876-025-04180-8 (2025)

Title: Association between gastrointestinal disorders and sleep-related problems: the mediating
effect of depression
Version: 3 Date: 02 Jun 2025
Reviewer's report:
Dear Authors,
Thank you for submitting your manuscript, which investigates the association between
gastrointestinal (GI) diseases and sleep disorders in NHANES 2005-2018 and explores
depression as a potential mediator. The topic is clinically meaningful and your use of a nationally
representative dataset is commendable. To help your work meet publication standards, I outline
below specific, actionable suggestions covering study design, statistical analysis, presentation
of results, and manuscript structure.
1. Study Design & Variable Definition
Cross-sectional nature – avoid causal wording
Because exposure, mediator, and outcome were measured simultaneously, replace terms such
as “risk,” “mediating effect,” “leads to” with “association,” “potential mediation,” etc. Please
revise the Abstract, Results, and Discussion accordingly.
GI-disease variable granularity
The single question “SP have stomach or intestinal illness?” mixes functional and organic
conditions and lacks diagnostic details. NHANES contains separate items for GERD, IBS, IBD,
peptic ulcer, etc. Either (i) conduct sensitivity analyses by specific diagnoses or (ii) explain this
limitation explicitly in Methods and Discussion.
Sleep-disorder outcome limitations
“Ever told doctor had trouble sleeping?” does not distinguish insomnia from sleep-disordered
breathing and lacks a time frame. Please add sensitivity analyses using other NHANES sleep
variables (sleep duration, physician-diagnosed sleep apnea, trouble falling asleep) or expand the
limitations section.
2. Statistical Analysis
Survey weighting and complex#sample design
Specify which weights were applied (WTMEC2YR or WTINT2YR), how you re-scaled them
across seven cycles, and the strata/PSU settings (code or appendix). Providing a comparison
table with and without weights will strengthen robustness.
Odds-ratio interpretation
For a binary exposure, OR = 1.98 means GI-disease participants have 98 % higher odds of sleep
disorders than those without GI disease—not “a 98 % increase per unit.” Similar wording errors
occur throughout; please correct them.
Mediation analysis transparency
Indicate the R package(s) used, whether survey weights were included, bootstrap iterations, and
report ACME/ADE with confidence intervals. Explain why the direction GI disease # depression
# sleep disorder is assumed despite cross-sectional data and cite supporting literature.
Unmeasured confounding
Important factors such as obstructive sleep apnea, chronic pain, physical activity, caffeine or
hypnotic use are absent. Discuss these as residual confounders or, if possible, adjust for them.
3. Presentation of Results
Table 1 restructuring
Break the very long baseline table into sub-sections (Demographics / Lifestyle / Comorbidities)
and consider moving the full version to Supplementary Material, retaining a concise version in
the main text.
Figures
Figure 2 (forest plot): add legends for p-interaction values, increase font/line weight, and supply
a high-resolution file (SVG).
Figure 3 (mediation diagram): show path coefficients clearly and use high-resolution graphics.
Consistency check
Ensure all ORs, CIs, and P-values match between text, tables, and abstract. Minor discrepancies
were noted.
4. Discussion & References
Mechanisms
Update the mechanistic discussion with recent (2023-2024) literature on the microbiome-sleep
axis, chrononutrition, and neuro-immuno-endocrine pathways.
Partial mediation by depression
Because depression explains ~30 % of the association, discuss other plausible pathways
(systemic inflammation, visceral hypersensitivity, metabolic factors).
Clinical implications
Suggest practical steps—e.g., routine sleep and depression screening (ISI, PHQ-2) for GI
patients—to enhance translational value.
5. Format & Editorial Points
Abstract exceeds the 350-word limit for BMC Gastroenterology—please condense.
Standardize spacing in “95 % CI” and use PIR < 1.55, BMI # 30.6 kg/m², etc.
Shorten the corresponding author’s phone number to an international format (+86-…).
Update several pre-2015 citations with newer systematic reviews.
6. Recommendation
Taking into account the methodological clarifications and additional analyses required, I
recommend Major Revision. Addressing the points above will substantially improve the rigor,
clarity, and impact of your study and should bring it to a publishable standard.
Best wishes for your revisions.