Metformin Contributes to the Therapeutic Effects of Acne Vulgaris by Modifying the Gut Microbiome

Background. Considering the increasing side effects of the first-line treatment for acne vulgaris, metformin was developed to be an effective adjunct therapy, but its mechanism of action is poorly defined. Recent evidence shows that the gut microbiota is a site of metformin action. The aim of this study was to evaluate the effects and mechanism of action for metformin in the adjuvant treatment of acne vulgaris by regulating gut microbiota. Methods. First, untreated acne patients were randomly allocated into two treatment groups. Both groups were treated with isotretinoin, but only one was additionally treated with metformin, for three months. Sprague Dawley (SD) rats were used as acne models, and they were also separated into groups that received isotretinoin, metformin, a combination of isotretinoin and metformin, and the vehicle, respectively. Then, the fecal samples from drug-intervention rats were transferred to germ-free rats with acne. The severity of the disease was evaluated using the Global Acne Grading System (GAGS) scoring for patients, and the number of comedones and mononuclear cells in pathological sections was used for rats. The composition of the gut microbiota was detected using gene sequencing for 16S rDNA. Results. Metformin had strong effects on the composition and function of the gut microbiota, and this correlated with the reduction in the severity of acne in both humans and rats. The fecal transfer to pseudo-germ-free rats improved both the inflammatory phenotype and comedones of acne in recipients of metformin-altered microbiota. Conclusion. The results suggest that metformin improves the symptoms of acne vulgaris by modulating the gut microbiota.