Gut Microbiota Composition Is Associated With the Global DNA Methylation Pattern in Obesity

Area of Science:

• Epigenetics
• Microbiome Research
• Metabolic Disease

Background:

• Obesity and related metabolic diseases involve gut microbiota and epigenetic alterations.
• A potential crosstalk exists between the gut microbiome and epigenome.
• The link between gut microbiome composition and epigenetic marks in obesity remains underexplored.

Purpose of the Study:

• To establish a link between gut microbiota and DNA methylation profiles in obese subjects.
• To identify candidate genes epigenetically regulated by gut microbiota in adipose tissue.

Main Methods:

• 16S rRNA gene sequencing analyzed gut microbiota in 45 obese subjects.
• Genome-wide DNA methylation profiling (Infinium EPIC BeadChip) was performed on blood and adipose tissue from selected high and low Bacteroidetes-to-Firmicutes ratio (BFR) groups.
• Gene expression of candidate genes was analyzed in adipose tissue using real-time quantitative PCR.

Main Results:

• Distinct DNA methylome patterns were observed between low and high BFR groups in both blood and adipose tissue.
• 258 genes showed differential methylation in both tissues.
• In adipose tissue, HDAC7 and IGF2BP2 were hypomethylated and overexpressed in the low BFR group, correlating with BFR and bacterial abundance.

Conclusions:

• DNA methylation status is associated with gut microbiota composition in obese individuals.
• Candidate genes (HDAC7, IGF2BP2) involved in glucose and energy homeostasis may be epigenetically regulated by gut bacteria in adipose tissue.