Review for 10.1186/s12876-025-04029-0 (2025)

Title: Association Between Blood Lead Levels and Constipation in Adults: Insights from
NHANES Data (2005–2010)
Version: 0 Date: 25 Mar 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-While the study mentions the inclusion of various data from NHANES, it doesn’t appear to
discuss in detail the potential confounders that could influence both blood lead concentration
and constipation (e.g., diet, lifestyle factors, co-existing health conditions). It would strengthen
the analysis to account for such factors and conduct a multivariable analysis to adjust for these
confounders.
-Constipation can be influenced by various factors such as diet (fiber intake), medication use
(e.g., opioids), and psychological factors (e.g., stress). These variables should be considered in
a more detailed manner.
-The introduction mentions the potential for blood lead exposure to affect gastrointestinal
motility, but there is little discussion on the underlying biological mechanisms that might explain
why elevated blood lead levels could be associated with constipation. A deeper dive into possible
physiological pathways would make the findings more compelling.
Understanding how lead toxicity could impact gut function would add theoretical depth to the
discussion.
-The study aims to explore a negative association between blood lead concentration and
constipation, which contrasts with previous research that suggests a positive relationship.
However, the study does not address why previous studies might have found a positive
association, or why this study might be finding an unexpected negative association.
-A thorough discussion on why this study’s results differ from previous studies and an
exploration of potential reasons (e.g., population differences, measurement methods, or
statistical analysis techniques) would help contextualize the findings.
-While the discussion mentions the cross-sectional nature of the study, the authors could place
even greater emphasis on the challenges of establishing causality. Given the nature of the data,
it is essential to underscore the importance of not inferring causal relationships from correlation
alone. The suggestion that higher lead levels may reduce the risk of constipation requires
cautious interpretation without clear longitudinal or experimental evidence to support a cause-
and-effect link.
-While the study does acknowledge potential confounders such as dietary habits and lifestyle
factors, it would benefit from further elaboration on how these could influence the relationship
between blood lead levels and constipation. For example, how might certain medications, diet
(e.g., fiber intake), or underlying medical conditions (e.g., diabetes) confound the observed
results? A more detailed exploration of these factors could help in understanding the complexity
of the relationship.
-While the discussion presents several potential mechanistic pathways, these are based on
existing literature and theoretical possibilities. More direct evidence or data to support these
pathways would strengthen the argument. For instance, if the study had any findings that
indirectly suggest gut microbiota changes or oxidative stress, that would help make the proposed
mechanisms more tangible.
-While NHANES is a large, nationally representative dataset, the study acknowledges that its
findings may not be fully applicable to populations outside of the U.S. However, the discussion
could benefit from further exploration of how geographic and cultural differences in lead
exposure, diet, and healthcare access might affect the generalizability of the results. This would
allow for more comprehensive implications of the study.