Comparison of diet and exercise on cardiometabolic factors in young adults with overweight/obesity: multiomics analysis and gut microbiota prediction, a randomized controlled trial

The optimal strategy for improving cardiometabolic factors (CMFs) in young obese individuals through diet and exercise remains unclear, as do the potential mechanisms. We conducted an 8-week randomized controlled trial to compare the effects of different interventions in youth with overweight/obesity. Gut microbes and serum metabolites were examined to identify regulating mechanisms. A total of 129 undergraduates were randomly assigned to fiber-rich (FR) diet, rope-skipping (RS), combined FR-RS and control groups. The results showed that single interventions were as effective as combined interventions in improving weight, waist circumference, body fat, and lipid profile compared with control group. Notably, the FR group further reduced low-density lipoprotein (LDL-C) and uric acid (UA) (all <i>p</i> < 0.05). Mediation analysis revealed four gut microbiota-metabolite-host axes in improving CMFs. Additionally, we used machine learning algorithms to further predict individual responses based on baseline gut microbiota composition, with specific microbial genera guiding targeted intervention selection. In conclusion, FR diet and/or RS were effective in improving CMFs, with the FR diet particular effectiveness in reducing LDL-C and UA levels. These benefits may drive by gut microbiome-metabolite-host interactions. Moreover, the predictability of gut microbiota composition supports making targeted decisions in selecting interventions. Trial Registration: NCT04834687.