Abstract
The aim of this study was to investigate the changes in the gut microbiota and proteins related to metabolism and immunity caused by childhood obesity and insulin resistance (IR) and to assess the underlying relationship between the gut microbiota and IR in children. Nineteen children with obesity and sixteen healthy children were recruited. Children with obesity were divided into two groups: obese with IR and obese without IR. All of the obese children participated in a 1-month lifestyle-based weight loss program. Faecal metagenomics and serum Olink proteomics combined with clinical parameters were used to identify the metabolic alterations associated with childhood obesity and IR. The gut microbiota and serum protein were significantly altered in obese children with IR. The relative abundances of Akkermansia muciniphila, IGFBP1 and GP6 were decreased in obese children with IR. Butyricicoccus sp. AM29-23AC, DLK1, CD163, CCL16 and CTSD levels were recovered after IR improved. TNFR1 had a significant indirect effect on the interaction between s-Citrobacter.freundii and fasting insulin. In conclusion, obese children with IR have abnormal gut microbiota and serum proteins related to metabolism and immunity, which can be improved after weight loss. The gut microbiome of children with obesity may contribute to the development of IR by triggering metabolic inflammation.Clinical Trial Registration: This study was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR2300072179).