Abstract
Childhood obesity is a newly emerging public health and an emerging concern in environmental health in rapidly urbanized areas of China. This preliminary study investigated the gut microbiome composition and toxic metabolite pathways of school-aged children in Nanjing. Using 16S rRNA sequencing and PICRUSt2-based functional predictions, we observed significant microbial structural changes between the normal weight group and the overweight/obese group, although α diversity was similar. Overweight and obese children exhibited a markedly higher Firmicutes/Bacteroidetes ratio as well as an enrichment of genera such as Subdoligranulum, Ruminococcus, and Lachnospira, indicating increased energy harvesting and inflammation. Functionally, the downregulation of tryptophan metabolism in obese children suggests a reduction in anti-inflammatory indole and an increase in the production of pro-inflammatory kynurenine. In contrast, the upregulation of thiamine metabolism may be linked to enhanced carbohydrate utilization and lipid biosynthetic activity. Our toxicology network analysis and molecular docking experiments suggest that AhR and thiamine-related metabolic enzymes are targets of tryptophan and thiamine metabolism, respectively, and that PPARG is also a potential molecular target mediating thiamine metabolism in childhood obesity. These findings highlight the environment-microbiome-host axis as a potential pathway for metabolic toxicity in childhood obesity. Further studies are needed to validate these toxicological mechanisms and identify microbial biomarkers for early intervention.