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Bariatric Surgery

Effects of obesity, and of weight loss following bariatric surgery, on methylation of DNA from the rectal mucosa and in cell-free DNA from blood

International Journal of Obesity volume 47, pages 1278–1285 (2023)Cite this article

Subjects

Abstract

Background

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.

Subjects and methods

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.

Results

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.

Conclusion

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.

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Fig. 1: Methylation (%) at specific genomic loci in DNA from rectal mucosal biopsies obtained from participants with obesity Pre-Surgery and at 6 months Post-Surgery and from Controls.
Fig. 2: Methylation (%) in cfDNA from serum at the following specific loci.

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Data availability

The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Human Nutrition Research Centre, Centre for Healthier Lives, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, England

    Khalil ElGendy, Fiona C. Malcomson, Sorena Afshar & John C. Mathers

  2. Surgery Department, Northumbria NHS Foundation Trust, Newcastle upon Tyne, England

    Khalil ElGendy, Sorena Afshar & Michael D. Bradburn

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  1. Khalil ElGendy
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Contributions

KE is the corresponding author, responsible for writing the manuscript, conducting the laboratory experiments, extracting and analysing data, interpreting results and creating figures and tables. FCM assisted in laboratory experiments, analysing data, laboratory work, analysing data, writing and revising the manuscript. SA designed and conducted the BOCABS study including ethical submission, recruitment and biological specimen collection. MB contributed to feedback and final revisions of the manuscript. JCM supervised the BOCABS study, including patient recruitment and sample collection, supervised laboratory work, provided feedback on the results and data analysis, and contributed to writing and revising the manuscript. All authors read and approved the final version of the manuscript.

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Correspondence to Khalil ElGendy.

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ElGendy, K., Malcomson, F.C., Afshar, S. et al. Effects of obesity, and of weight loss following bariatric surgery, on methylation of DNA from the rectal mucosa and in cell-free DNA from blood. Int J Obes 47, 1278–1285 (2023). https://doi.org/10.1038/s41366-023-01384-4

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