Impact of Low-Dose Oral Minocycline (DFD-29) on Skin, Gastrointestinal, and Vaginal Microflora in Healthy Adults

December 2025 | Volume 24 | Issue 12 | 1222 | Copyright © December 2025


Published online November 30, 2025

Richard L. Gallo MD PhDa, Hilary Baldwin MDb, Julie Harper MDc, Neal Bhatia MDd, John A. McLane PhDe, Srinivas Sidgiddi MDf

aDepartment of Dermatology, University of California, San Diego, San Diego, CA
bMedical Director, The Acne Treatment and Research Center, Brooklyn, NY;
Robert Wood Johnson Medical Center, Rutgers University, New Brunswick, NJ
cDermatology and Skin Care Center of Birmingham, Birmingham, AL
dTherapeutics Clinical Research, San Diego, CA
eCatawba Research, Charlotte, NC
fJourney Medical Corporation, Scottsdale, AZ

Abstract
Background: DFD-29 (minocycline hydrochloride extended-release capsules, 40 mg) has shown significant therapeutic benefit vs placebo and doxycycline in treating moderate-to-severe rosacea. However, the impact of its use on skin, vaginal, and gastrointestinal microbiota is unknown.
Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, 60 healthy adults were randomized in a 2:1 ratio to receive either DFD-29 (40 mg) orally or a matching placebo once daily for 16 weeks. Microbiological samples were collected from the skin (forehead), vagina, and stool at baseline and weeks 4, 8, and 16 to evaluate changes in normal microbiota species (via culture and 16S rRNA sequencing), in the MIC90 of selected colonized microbial species, and in opportunistic microbiota with DFD-29 vs placebo. Safety was evaluated via analysis of adverse events, vital signs, and laboratory tests.
Results: Thirty-eight adults assigned to DFD-29 and 19 adults assigned to placebo were included in the microbiota evaluable population. There were no significant differences detected in the abundance of microbial species in the skin, stool, or vagina from baseline to week 16 between the DFD-29 and placebo groups. No significant differences were detected in resistance to minocycline between DFD-29 and placebo. There were also no significant differences in the presence of opportunistic microbiota at any time point. No significant safety issues were reported.
Conclusion: Administration of DFD-29 for 16 weeks had no detectable effects on skin, GI tract, or vaginal microflora and was well tolerated in healthy adults, reinforcing its potential as a therapeutic option in moderate-to-severe rosacea.

 

INTRODUCTION

Rosacea is a chronic inflammatory facial skin disease that affects 5% to 10% of the population and can adversely affect quality of life.1,2 Common signs and symptoms of rosacea include skin erythema, the development of erythematous papules and pustules, flushing, telangiectasia, phymatous changes, and ocular manifestations.3,4 While its pathogenesis is not fully understood, it is believed to be multifaceted and involves immune and inflammatory dysregulation, neurovascular dysregulation, microbiome dysbiosis, and genetics.5-10 Systemic antibiotics, such as minocycline and doxycycline, are frequently used to control rosacea symptoms.

Minocycline is a chemically modified, second-generation, broad-spectrum tetracycline that effectively targets a wide range of Gram-positive and Gram-negative bacteria and atypical organisms,11 preventing bacterial growth by inhibiting protein synthesis.12 It also exhibits potent anti-inflammatory properties.11

A low-dose formulation of minocycline hydrochloride (HCl), DFD-29, has shown superior therapeutic benefit vs placebo and doxycycline in treating rosacea and has recently been approved for this indication by the US Food and Drug Administration under the brand name of EmrosiTM (minocycline hydrochloride).13-15 However, the impact of DFD-29 on skin, gastrointestinal (GI), and vaginal microbiota is unknown. This study evaluated whether treatment with DFD-29 results in shifts in the normal microbiota of the skin, GI tract, or vagina, the development of resistance to minocycline, and the appearance of or increase in opportunistic microbiota (yeast or opportunistic bacteria).
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