Association between total body water and the risk of gastrointestinal symptoms: evidence from NHANES and Mendelian randomization analyses

BACKGROUND: Total body water (TBW) is an important indicator of fluid homeostasis and is closely related to various metabolic and chronic diseases. However, the relationship between TBW and gastrointestinal symptoms (stomach or intestinal illness, SII) remains unclear. Most previous studies were observational and lacked causal inference. This study, based on data from the National Health and Nutrition Examination Survey (NHANES, 2001-2018) and combined with two-sample Mendelian randomization (MR), explored the nonlinear relationship and potential causal association between TBW and gastrointestinal symptoms from both epidemiological and genetic perspectives. METHODS: Using cross-sectional data from the NHANES (2001-2018), logistic regression, restricted cubic spline (RCS), and subgroup analyses were performed to explore the association between TBW and gastrointestinal symptoms. A two-sample MR study was subsequently conducted using genome-wide association study (GWAS) summary statistics to determine the causal relationship between body water mass (BWM) and gastrointestinal or abdominal diseases. RESULTS: From the NHANES, 36,043 participants aged ≥ 20 years were included. Baseline analysis revealed a significant difference in TBW between participants with and without gastrointestinal symptoms. Logistic regression confirmed that the association between TBW and gastrointestinal symptoms was robust across models. RCS analysis suggested a potential nonlinear pattern, although formal testing did not support significant nonlinearity (P = 0.551). Within the range of 24.9-38.5 L, TBW was associated with lower odds of gastrointestinal symptoms (odds ratio (OR) < 1), whereas values above 38.5 L were associated with higher odds (OR > 1). In subgroup analysis, the high-TBW group (> 38.5 L) was associated with increased risk, whereas the low-TBW group (< 38.5 L) showed a protective association. CONCLUSION: There is a potential nonlinear relationship between TBW and the risk of gastrointestinal symptoms. However, as TBW is strongly correlated with body size and adiposity, the associations may be largely driven by obesity-related factors rather than by water balance. MR analysis provided suggestive evidence supporting a causal association between TBW and gastrointestinal or abdominal diseases. Maintaining an appropriate water balance may help reduce gastrointestinal symptoms, but these findings should be interpreted with caution, and further studies incorporating comprehensive body composition measures are needed.