4. Discussion
obesity, weight reduction
OBESITY, OBESE
In this clinical trial designed to examine metabolic differences between normal-weight children and children with obesity, including between before and after lifestyle interventions, we found that imbalances in microbiota and metabolites were associated with both obesity and response to the intervention.We found that serum isoleucine (a BCAA) was increased owing to obesity, which was consistent with previous studies showing increased isoleucine in obese rats and overweight/obese subjects [Inosine and uric acid, which are products of purine metabolism, were increased in participants with obesity. In mice that were fed a high-fat diet, these increased metabolites were associated with gut dysbiosis [We found that serum bile acids, especially TDCA and TMCA (α + β), were decreased in participants with obesity, consistent with previously reported studies, in which systemic TDCA levels decreased significantly in diet-induced obese animal models and high-fat diet subjects, and were restored after bariatric surgery [We performed an obesity intervention program to identify metabolic pathways with therapeutic relevance. Interestingly, fecal myristic acid increased significantly in participants with obesity at baseline. However, urinary myristic acid decreased significantly after the lifestyle intervention. A significant correlation was observed between urinary myristic acid and Overall, the levels of intermediates in fatty acid biosynthesis were significantly lower in patients who responded to the intervention. Increased fatty acid biosynthesis positively correlates with BMI [Several integrative interventional studies on obesity have combined metabolites and microbiota; however, most were conducted in adults and not children. To our knowledge, this is the first integrative interventional study to investigate alterations in the gut microbiota and metabolites in the serum, urine, and feces of participants with pediatric obesity. Our findings suggest a possible pathway for weight reduction and therapeutic targets.Our study has several limitations. We identified significantly altered metabolites after the intervention; however, their numbers were small. These findings may be a consequence of the small number of participants, a short period of intervention, and a controlled before-and-after study design. A longitudinal randomized controlled study with larger sample sizes is required in the future. Additionally, targeted metabolomics could be considered to validate the altered metabolites associated with obesity in this study. Because the 16S rRNA gene amplicon sequencing for metagenome analysis identifies genus-level changes, species-level changes and actual functional profiling could not be identified. Finally, this study was limited to Korean children, and our findings should be validated in other ethnicities and adults. To further confirm the role of gut microbiota in obesity, additional in vitro experimental studies are required to demonstrate the production and transport of these altered metabolites.