DNA甲基化是一种表观遗传机制，通过它，包括营养和炎症在内的环境因素可以影响健康。肥胖是许多常见疾病的一个主要可改变危险因素，包括心血管疾病和癌症。具体而言，由于异常甲基化的炎症基因所导致的肥胖诱发炎症可能会增加数种非传染性疾病的风险，包括结直肠癌（CRC）。本研究首次探讨了通过胃肠吻合手术（BS）引起的减重对直肠和血液中细胞游离DNA（cfDNA）DNA甲基化的影响。在肥胖参与者中，我们测量了28个参与者BS前后6个月的直肠黏膜活检和血清cfDNA中的DNA甲基化情况，同时还包括12个无肥胖的参与者（对照组），对照组参与者与肥胖者在年龄和性别上匹配，数据来自Biomarkers Of Colorectal cancer After Bariatric Surgery（BOCABS）研究。我们通过焦化测序法测定了LEP、IL6、POMC、LINE1、MAPK7和COX2的DNA甲基化情况。术前肥胖组BMI显著下降，从41.8 kg/m2下降到BS后6个月的32.3 kg/m2。与对照组相比，肥胖与直肠黏膜和血清cfDNA中LEP甲基化水平较低相关。BS使直肠黏膜DNA中LEP的甲基化水平恢复正常，而cfDNA中未能恢复。BS使直肠黏膜DNA和cfDNA中的LINE1的某些CpG位点甲基化水平降低到与无肥胖参与者相似的水平。BS使直肠黏膜DNA中的POMC甲基化在6个月后恢复正常。BS使肥胖患者的直肠粘膜中的LINE1、POMC和LEP甲基化水平恢复到与无肥胖个体相似的水平。这些发现支持BS引起的减重对其他组织DNA甲基化的可逆性的当前证据。直肠粘膜中的DNA甲基化变化有望成为客观评估减重干预对癌症和其他疾病风险影响的生物标志物。© 2023. 作者，Springer Nature Limited独家许可。

DNA methylation is an epigenetic mechanism through which environmental factors including nutrition and inflammation influence health. Obesity is a major modifiable risk factor for many common diseases including cardiovascular diseases and cancer. In particular, obesity-induced inflammation resulting from aberrantly-methylated inflammatory genes may drive risk of several non-communicable diseases including colorectal cancer (CRC). This study is the first to investigate the effects of weight loss induced by bariatric surgery (BS) on DNA methylation in the rectum and in cell-free DNA (cfDNA) from blood.DNA methylation was quantified in rectal mucosal biopsies and cfDNA from serum of 28 participants with obesity before and 6 months after BS, as well as in 12 participants without obesity (control group) matched for age and sex from the Biomarkers Of Colorectal cancer After Bariatric Surgery (BOCABS) Study. DNA methylation of LEP, IL6, POMC, LINE1, MAPK7 and COX2 was quantified by pyrosequencing.BMI decreased significantly from 41.8 kg/m2 pre-surgery to 32.3 kg/m2 at 6 months after BS. Compared with the control group, obesity was associated with lower LEP methylation in both the rectal mucosa and in cfDNA from serum. BS normalised LEP methylation in DNA from the rectal mucosa but not in cfDNA. BS decreased methylation of some CpG sites of LINE1 in the rectal mucosal DNA and in cfDNA to levels comparable with those in participants without obesity. Methylation of POMC in rectal mucosal DNA was normalised at 6 months after BS.BS reversed LINE1, POMC and LEP methylation in the rectal mucosa of patients with obesity to levels similar to those in individuals without obesity. These findings support current evidence of effects of BS-induced weight loss on reversibility of DNA methylation in other tissues. The DNA methylation changes in the rectal mucosa shows promise as a biomarker for objective assessment of effects of weight loss interventions on risk of cancer and other diseases.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.