Abstract

Introduction: Weight-loss diet interventions affect gut microbiota-related metabolites, such as trimethylamine N-oxide (TMAO) and its precursors (choline and L-carnitine), and improve cardiometabolic status. However, little is known about how these metabolites may affect bone mineral density (BMD) during weight loss. Hypothesis: We assessed the hypothesis that changes in gut microbiota-related metabolites are related to changes in BMD during weight loss. Methods: A total of 264 overweight and obese participants with measurement of BMD by dual-energy X-ray (DEXA) scan were included in the present analysis. The participants were randomly assigned to one of four diets varying in macronutrient intakes. We investigated the associations of changes in plasma levels of TMAO, choline, and L-carnitine from baseline to 6 months with changes in BMD. Results and Conclusions: We found that changes in plasma levels of TMAO from baseline to 6 months were positively related to changes of whole body ( P =0.011) and spine ( P =0.002) BMD over the 2-year intervention, independent of weight change. The association with whole body BMD was also significant at 6 months. The correlations between changes in TMAO and BMD were not modified by dietary macronutrients; while changes in TMAO precursor L-carnitine showed interactions with dietary fat intake on changes of spine and trochanter BMD (all P <0.05). Participants with the least L-carnitine decrease showed less BMD reduction by eating a low-fat diet ( P spine =0.031 and P trochanter =0.017). In conclusion, our results suggest that decrease in TMAO during weight loss may be related to reduction in BMD.

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