Review for 10.1186/s12876-025-03784-4 (2025)

Title: Association between Atherogenic Index of Plasma and Chronic Diarrhea: A Cross-
Sectional Study of the NHANES 2005-2010
Version: 1 Date: 20 Feb 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the sample size is noted as determined based on available data, it would strengthen the
methodology to mention whether any power calculations were conducted to assess the adequacy
of the sample size for detecting significant effects. Power analysis helps assess whether the study
has sufficient statistical power to detect a meaningful effect.
-While AIP has been linked to various cardiovascular and metabolic conditions, more explicit
mention of why it is hypothesized to be particularly relevant for CD (aside from its connection
to inflammation and insulin resistance) could enhance the argument. A brief discussion on how
AIP could act as a systemic indicator of lipid-related changes that affect gut function would
clarify its importance in this context.
-Although the study addresses various demographic and health-related covariates, including
behavioral factors like tobacco use and alcohol consumption, it might be beneficial to include a
discussion on how dietary habits (especially fat intake) were accounted for. Since lipids and gut
microbiota are key factors in the development of CD, dietary patterns might also be an important
variable to consider.
-The Bowel Health Questionnaire is used to screen for CD, but further clarification could be
helpful on how this tool was administered. Were participants given a self-report questionnaire,
or were medical records also consulted? Providing more detail on how the symptom of CD was
diagnosed would improve the understanding of the study design.
-The study mentions several chronic conditions (e.g., diabetes, hypertension, depression), but
other factors related to gut health (such as the use of antibiotics or gastrointestinal medications)
are not mentioned. Including these would further refine the control for confounding and could
help pinpoint more specific mechanisms linking AIP and CD.
-While the discussion includes several plausible hypotheses for the observed association
between AIP and CD, some additional detail could help further clarify how each hypothesis
specifically relates to the study's findings. For example, while chronic inflammation is
highlighted as a key mechanism, it would be helpful to briefly explain how AIP itself might
contribute to or reflect inflammation in the context of CD. This would tie the findings back to
the proposed biological mechanisms more concretely.
-The hypothesis regarding the absorption of endotoxins (such as LPS) during lipid digestion
could be explored further. Is there evidence from prior studies that suggests AIP might correlate
with LPS absorption, or is this a theoretical extension of the current findings? A clearer
connection could strengthen the discussion of the mechanism.
-Although the study mentions the potential impact of diet (e.g., high-fat diets causing dysbiosis
and dysregulated lipid metabolism), the specific role of dietary habits in this study is only briefly
alluded to. Since diet is a key driver of lipid metabolism and gut health, more attention could
be paid to how dietary factors might influence both AIP and the development of CD. Given that
this study uses NHANES data, it might be worth discussing whether dietary intake was assessed
and if it was controlled for in the analysis.
-The discussion mentions that AIP might serve as a marker linking dyslipidemia and obesity to
CD risk, but this could be expanded upon. For example, is it possible that individuals with higher
AIP are more likely to have metabolic disturbances that lead to gut inflammation or altered
gut permeability, thus contributing to CD? A deeper dive into how AIP could specifically link
lipid abnormalities to the pathogenesis of CD would provide more insight into its potential as
a biomarker.