Liu Lujie, Li Meng, Qin Yujie, Liu Yuesheng, Li Min, Lian Biyao, Guo Ruilong, Xiao Yanfeng, Yin Chunyan
Department of Pediatrics, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xiwu Road, Xi'an, 710061, Shaanxi, China.
Sci Rep. 2025 Jul 1;15(1):21436. doi: 10.1038/s41598-025-07357-z.
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).
本研究旨在调查儿童肥胖和胰岛素抵抗（IR）引起的肠道微生物群以及与代谢和免疫相关的蛋白质的变化，并评估儿童肠道微生物群与IR之间的潜在关系。招募了19名肥胖儿童和16名健康儿童。肥胖儿童分为两组：伴有IR的肥胖儿童和不伴有IR的肥胖儿童。所有肥胖儿童都参加了为期1个月的基于生活方式的减肥计划。采用粪便宏基因组学和血清Olink蛋白质组学结合临床参数来识别与儿童肥胖和IR相关的代谢改变。伴有IR的肥胖儿童的肠道微生物群和血清蛋白有显著改变。伴有IR的肥胖儿童中嗜黏蛋白阿克曼氏菌、胰岛素样生长因子结合蛋白1（IGFBP1）和糖蛋白6（GP6）的相对丰度降低。IR改善后，丁酸球菌属AM29 - 23AC、前体蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）、CD163、C - C基序趋化因子16（CCL16）和组织蛋白酶D（CTSD）水平恢复。肿瘤坏死因子受体1（TNFR1）对弗氏柠檬酸杆菌与空腹胰岛素之间的相互作用有显著间接影响。总之，伴有IR的肥胖儿童存在与代谢和免疫相关的肠道微生物群和血清蛋白异常，减肥后可得到改善。肥胖儿童的肠道微生物群可能通过引发代谢炎症促进IR的发展。临床试验注册：本研究已在中国临床试验注册中心注册（注册号：ChiCTR2300072179）。
