Machine Learning Reveals Influence of Stool pH on Bone Mineral Density in a Healthy Multi-Ethnic U.S. Population

Abstract

Objectives A variety of modifiable and non-modifiable factors such as ethnicity, age, and diet have been shown to influence bone health. Previous studies are usually limited to analyses focused on the association of a few a priori variables or on a specific subset of the population. The objective of this study was to use dietary, physiological, and lifestyle data to identify directly modifiable and non-modifiable variables predictive of bone mineral content (BMC) and bone mineral density (BMD) in healthy US men and women using machine learning models. Methods Ridge, lasso, elastic net, and random forest models were used to predict whole-body, femoral neck, and spine BMC and BMD in healthy US adults (n = 313) using non-modifiable anthropometric, physiological, and demographic variables, directly modifiable lifestyle (physical activity, tobacco use) and dietary (nutrient or food groups intake via food frequency questionnaire) variables, and variables approximating directly modifiable behavior (circulating vitamin D and stool pH). Model feature importances were used to identify variables useful for predicting BMC and BMD. Results Machine learning models using non-modifiable variables explained more variation in BMC and BMD (highest R2 = 0.750) compared to when using only directly modifiable variables (highest R2 = 0.107). Machine learning models had better performance compared to multivariate linear regression, which had lower predictive value (highest R2 = 0.063) when using directly modifiable variables only. BMI, body fat %, height, and menstruation history were predictors of BMC and BMD. For the directly modifiable features, betaine, cholesterol, hydroxyproline, menaquinone-4, dihydrophylloquinone, eggs, cheese, cured meat, refined grains, fruit juice, and alcohol consumption were predictors of BMC and BMD. Low stool pH, a proxy for fermentable fiber intake, was also predictive of higher BMC and BMD. Conclusions Machine learning models can be used to identify previously unforeseen variables that may contribute to bone health. Modifiable factors explained less variation in the data compared to other features. Low stool pH, which has been shown to be associated with fermentable fiber intake, short chain fatty acid production, and enhanced calcium absorption, was associated with higher BMC and BMD in a healthy US population. Funding Sources USDA-ARS