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: 04 Jun 2025
Reviewer's report:
While the topic of this study is clinically relevant and the use of a nationally representative
dataset such as NHANES adds value, there are several methodological, structural, and reporting
issues that must be addressed. These concerns affect the scientific clarity and overall credibility
of the study. Substantial revision is required before the manuscript can be considered for
publication.
1. Introduction
The introduction lacks several essential components. Specifically:
Burden of disease: There is no mention of the prevalence or public health impact of either
gastrointestinal disorders or sleep disorders.
Rationale: The biological and clinical reasoning for exploring this association is too vague and
lacks adequate citations.
Study objectives: The manuscript does not clearly define its aims or research questions.
Conceptual framework: The choice to include depression as a mediating factor is not
theoretically justified in the introduction.
Many sentences in this section are written in general terms and lack proper referencing.
2. Methods
Exposure Variable
The exposure is defined using a vague, self-reported NHANES questionnaire item: “SP have
stomach or intestinal illness?” This lacks clinical specificity and introduces high risk of
misclassification bias. The authors should clarify exactly what is captured by this item.
It is also unclear whether gastrointestinal cancers were included in the exposure definition.
Outcome Variable
The dependent variable is based on the question: “Ever told doctor had trouble sleeping?” This
single-item self-report is overly broad and does not differentiate between types or severities of
sleep disorders.
Analyzing  components such as sleep duration, sleep latency, and wake frequency would provide
more valid and granular insights.
Covariates
Both continuous and categorical versions of variables such as BMI, PIR, and age were
reportedly adjusted for in regression models. Including both forms simultaneously can introduce
multicollinearity and should be avoided or justified.
Statistical Analysis
The statistical analysis section needs to be more precise. For example:
It is not clear how the subgroup and mediation analyses were planned or executed.
The interaction analysis results (Pint) are reported, but the statistical model behind them is not
explained.
The mediation analysis lacks methodological clarity. The type of analysis (e.g., causal
mediation, path analysis, or logistic regression-based) should be explicitly described.
3. Results
Descriptive Statistics
The authors do not describe how they handled missing data.
Exclusion criteria, if any, are not discussed.
Logistic Regression Models
Including both continuous and tertile (categorized) variables in the same model, such as BMI or
PIR, suggests multicollinearity. This should be re-evaluated.
The manuscript incorrectly interprets odds ratios. For example, stating that “the incidence of
sleep problems increased by 98% for each additional unit of GI disease” is misleading. The
exposure variable is binary, so this interpretation is not valid.
Subgroup Analysis
The subgroup findings are not coherently interpreted. Some effects are reported as statistically
significant in text but are visually marginal in the forest plot.
Mediation Analysis
While the authors report the proportions of mediation and present ORs for direct, indirect, and
total effects, the statistical method remains unclear.
4. Discussion
The first two paragraphs of the discussion are general summaries of the results and should be
removed. Repetition of results adds little value to this section.
There are several mechanistic explanations (e.g., about serotonin, vagus nerve, inflammation,
ghrelin, leptin) presented without proper referencing or relevance to the study’s findings.
The rationale and interpretation of depression as a mediator is inadequately explained. The
discussion should explore why depression was chosen, how it may interact biologically and
psychologically with both GI disorders and sleep, and how this finding aligns with previous
research.
Limitations are acknowledged but are inconsistently addressed:
There is no mention of residual confounding or bias due to self-reported exposure and outcome.
Recommendations such as screening for GI dysfunction in patients with sleep disorders are not
supported by cross-sectional data and should be removed or rephrased cautiously.
5. Conclusion
The conclusion overstates the findings. The use of causal or recommendation-based language
(e.g., "screening is recommended") is inappropriate given the cross-sectional design.
The final recommendation should be toned down and framed as a hypothesis-generating
observation rather than a clinical recommendation.
6. Acknowledgements
The current acknowledgment section uses informal and personal language (e.g., "relatives and
friends") which is not appropriate for a scientific manuscript. It should be revised or removed.