Effect of combined probiotics and doxycycline therapy on the gut–skin axis in rosacea

ABSTRACT Rosacea is a chronic inflammatory skin condition marked by facial erythema, telangiectasia, and acne-like eruptions, affecting millions worldwide. While antibiotics remain a common treatment, prolonged use has significant adverse effects and can lead to antibiotic resistance. This study evaluated the impact of combined probiotics and doxycycline treatment on rosacea, emphasizing the gut–skin axis. Sixty rosacea patients were randomly assigned to the probiotic, placebo, or control groups. After a 2-week doxycycline treatment, participants underwent a 3-month intervention with either a placebo, probiotic, or no further treatment. Clinical outcomes were assessed at baseline and after the 14-week intervention. Our results showed that probiotic administration improved facial skin conditions, alleviated inflammation, and reduced facial skin microbiota diversity while enhancing gut microbiota heterogeneity. Multivariate analysis identified microbial markers distinguishing the probiotic group from the control and placebo groups, and some markers were associated with skin health parameters. After the probiotic intervention, some facial skin-associated taxa, such as Aquabacterium sp., UBA4096 sp. 1, UBA4096 sp. 2, and Yimella indica , decreased in abundance. Additionally, the fecal microbiota of the probiotic group was enriched in specific gut microbes, including Streptococcus parasanguinis , Erysipelatoclostridium ramosum , and Coprobacillus cateniformis , while showing a reduced abundance of Bacteroides vulgatus . These changes were associated with reduced facial sebum levels and a lower physician’s global assessment score. Finally, fewer antibiotic resistance genes, particularly tetracycline resistance genes, were detected in the probiotic group compared with the control and placebo groups. Our study supports the existence of a gut–skin axis and the application of probiotics in managing rosacea. IMPORTANCE This research elucidates rosacea management with novel insights into probiotic use alongside doxycycline, showing dual benefits in symptom relief and inflammation reduction in patients. The study maps probiotic-induced shifts in gut and skin microbiota, underscoring microbial shifts correlating with skin health improvements. Crucially, it deciphers the gut–skin axis modulation by probiotics, proposing a method to curb antibiotic resistance in rosacea therapies. This study furnishes robust evidence for probiotics in rosacea, advancing our grasp of the gut–skin relationship.