Genetically determined SCFA concentration modifies the association of dietary fiber intake with changes in bone mineral density during weight loss: The Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.

BACKGROUND SCFAs are involved in regulation of body weight and bone health. OBJECTIVES We aimed to examine whether genetic variations related to butyrate modified the relation between dietary fiber intake and changes in bone mineral density (BMD) in response to weight-loss dietary interventions. METHODS In the 2-y Preventing Overweight Using Novel Dietary Strategies trial, 424 participants with BMD measured by DXA scan were randomly assigned to 1 of 4 diets varying in macronutrient intakes. A polygenic score (PGS) was calculated based on 7 genetic variants related to the production of butyrate for 370 of the 424 participants. RESULTS SCFA PGS significantly modified the association between baseline dietary fiber intake and sex on 2-y changes in whole-body BMD (P-interaction = 0.049 and 0.008). In participants with the highest tertile of SCFA PGS, higher dietary fiber intake was related to a greater increase in BMD (β:  0.0022; 95% CI: 0.0009, 0.0035; P = 0.002), whereas no such association was found for participants in the lower tertiles. In the lowest tertiles of SCFA PGS, men showed a significant increase in whole-body BMD (β: 0.0280; 95% CI: 0.0112, 0.0447; P = 0.002) compared with women. In the highest tertile, no significant difference was found for the change in BMD between men and women. CONCLUSIONS Our data indicate that genetic variants related to butyrate modify the relations of dietary fiber intake and sex with long-term changes in BMD in response to weight-loss diet interventions.