Notably, through a comprehensive analysis of the existing literature, we found that there is an intersection between DNA methylation and gut microbiota in the pathways and mechanisms involved in the occurrence and development of obesity, such as diet, the microbiota–gut–brain axis, adipose tissue development, differentiation and function, lipid metabolism, glucose metabolism, insulin resistance, immune inflammatory response, and Vit D metabolism. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.