Topical Application of Engineered Lactobacillus Reuteri With a Zinc Sulfate-Tannic Acid MPN Coating for Acne

Evaluating Engineered Lactobacillus Reuteri With a Zinc Sulfate-Tannic Acid MPN Coating for Acne: A Double-Blind, Randomized Controlled Trial

A growing body of evidence suggests that the development and progression of acne are closely linked to an imbalance in the skin's microbial community. Compared to healthy skin, the composition and function of the microbiota in acne lesions are significantly altered. This microbial imbalance is believed to drive the formation and recurrence of acne through mechanisms such as triggering abnormal inflammatory responses and compromising the skin barrier.

An in-depth exploration of the interaction between acne and the skin microbiome not only offers new perspectives for understanding the root causes of the disease but also lays the groundwork for developing novel treatment strategies aimed at modulating the microbiota. Therefore, identifying innovative approaches that integrate acne treatment with the regulation of microbial balance holds significant clinical and social value.

Although existing acne treatments have made progress, research focusing on interventions that regulate the local skin microecology through probiotics remains relatively limited. This study aims to explore a new strategy based on skin microecological modulation. Investigators are using a common probiotic-Lactobacillus reuteri-and applying an engineering modification with a special coating formed by zinc sulfate and tannic acid (MPN coating). This modification is intended to enhance the bacterium's survival and colonization on the skin, thereby more effectively regulating the local microbiota and reducing inflammation.

This study is a rigorous scientific clinical trial designed as randomized, double-blind, and controlled. Eligible participants will be randomly assigned to one of four groups, receiving either the engineered Lactobacillus reuteri cream, the plain Lactobacillus reuteri cream, a simple moisturizing cream (placebo), or an already-marketed effective cream (tretinoin cream). The treatment will last for 2 weeks, followed by an 8-week observation period. Efficacy and safety will be evaluated through professional assessments.

Our goal is to scientifically evaluate the safety and efficacy of this new therapy, hoping to provide a potential new treatment option for individuals with acne and explore new pathways for improving skin health.

Study Overview

• Status: Recruiting
• Conditions: Acne
• Intervention / Treatment: Biological: MPN-coated engineered Lactobacillus reuteri cream; Drug: Tretinoin cream 0.1%; Drug: Petrolatum-glycerin cream; Biological: Plain Lactobacillus reuteri cream

• Study Type: Interventional
• Enrollment (Estimated): 196
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jianglin Zhang; Phone Number: +86 13873143466; Email: zhang.jianglin@szgospital.com

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China
      • Recruiting
      • Shenzhen People's Hospital
      • Contact: Shenzhen People's Hospital; Phone Number: +86 75522943881; Email: 195323995@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects must be diagnosed with acne (based on history, clinical manifestation, and dermatoscopy) and classified as Grade I to III per the International Improved Grading System.
2. Subjects must be willing and able to provide written informed consent.
3. Subjects must be 18 to 33 years of age and in generally good health.
4. Subjects must have more than 9 inflammatory lesions.

Exclusion Criteria:

1. Have used antibiotics within 1 month before the study start.
2. Have used systemic retinoid therapy within 3 months before the study start.
3. Have undergone any other acne treatment within 1 month before the study start.
4. Have any other condition that the investigator considers would make participation unsuitable (e.g., deemed unreliable, non-compliant, or unable to comprehend the study assessments).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group; Apply the MPN-coated engineered Lactobacillus reuteri cream to acne lesions once daily for 2 weeks.	Biological: MPN-coated engineered Lactobacillus reuteri cream; Each night before bedtime, after washing the face, an appropriate amount of MPN-coated engineered Lactobacillus reuteri cream should be applied topically to acne lesions using a sterile cotton swab. The area should not be washed immediately after application. Normal face washing can be resumed the following morning. This regimen should be continued for 2 weeks.
Active Comparator: Positive Control Group; Apply the 0.1% tretinoin cream to acne lesions once daily for 2 weeks.	Drug: Tretinoin cream 0.1%; Each night before bedtime, after washing the face, an appropriate amount of 0.1% tretinoin cream should be applied topically to acne lesions using a sterile cotton swab. The area should not be washed immediately after application. Normal face washing can be resumed the following morning. This regimen should be continued for 2 weeks.
Placebo Comparator: Negative Control Group; Apply the petrolatum-glycerin cream to acne lesions once daily for 2 weeks.	Drug: Petrolatum-glycerin cream; Each night before bedtime, after washing the face, an appropriate amount of petrolatum-glycerin cream should be applied topically to acne lesions using a sterile cotton swab. The area should not be washed immediately after application. Normal face washing can be resumed the following morning. This regimen should be continued for 2 weeks.
Other: Control Group; Apply the plain Lactobacillus reuteri cream to acne lesions once daily for 2 weeks.	Biological: Plain Lactobacillus reuteri cream; Each night before bedtime, after washing the face, an appropriate amount of plain Lactobacillus reuteri cream should be applied topically to acne lesions using a sterile cotton swab. The area should not be washed immediately after application. Normal face washing can be resumed the following morning. This regimen should be continued for 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in acne count at Week 8 relative to the baseline.	Facial photographs of patients are taken before treatment and at Weeks 1, 2, 4, and 8 after the initial treatment. Dermatologists count the number of acne lesions from these photographs. The percentage change in acne count at Week 8 relative to the baseline is calculated as: (Acne count at Week 8 - Acne count at baseline) / Acne count at baseline × 100%.	Facial photographs of the patients will be taken at baseline and at Weeks 1, 2, 4, and 8 after the initial treatment, and the number of acne lesions will be counted by dermatologists.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in the number of inflammatory acne lesions at Week 8 relative to the baseline	Facial photographs of patients are taken before treatment and at Weeks 1, 2, 4, and 8 after the initial treatment. Dermatologists count the number of inflammatory acne lesions from these photographs. The percentage change in the number of inflammatory acne lesions at Week 8 relative to the baseline is calculated as: (Number of inflammatory acne lesions at Week 8 - Number of inflammatory acne lesions at baseline) / Number of inflammatory acne lesions at baseline × 100%.	Facial photographs of the patients will be taken at baseline and at Weeks 1, 2, 4, and 8 after the initial treatment, and the number of inflammatory acne lesions will be counted by dermatologists.
Percentage change in the number of non-inflammatory acne lesions at Week 8 relative to the baseline	Facial photographs of patients are taken before treatment and at Weeks 1, 2, 4, and 8 after the initial treatment. Dermatologists count the number of non-inflammatory acne lesions from these photographs. The percentage change in the number of non-inflammatory acne lesions at Week 8 relative to the baseline is calculated as: (Number of non-inflammatory acne lesions at Week 8 - Number of non-inflammatory acne lesions at baseline) / Number of non-inflammatory acne lesions at baseline × 100%.	Facial photographs of the patients will be taken at baseline and at Weeks 1, 2, 4, and 8 after the initial treatment, and the number of non-inflammatory acne lesions will be counted by dermatologists.
Changes in the relative abundance of Propionibacterium, Lactobacillus, and Staphylococcus in acne-prone skin from baseline to Week 8	Skin microbiome samples are collected from acne lesions before treatment and at Weeks 1, 2, 4, and 8 after the initial treatment. These samples are subjected to 16S rRNA gene sequencing to detect the presence and relative abundance of various bacterial taxa in the affected areas following the intervention.	Skin microbiome samples are collected from acne lesions at baseline and at Weeks 1, 2, 4, and 8 after the initial treatment.

Collaborators and Investigators

• Sponsor: Shenzhen People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2025
• Primary Completion (Estimated): March 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: January 17, 2026
• First Submitted That Met QC Criteria: January 17, 2026
• First Posted (Actual): January 26, 2026

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: acne; Lactobacillus reuteri
• Additional Relevant MeSH Terms: Skin Diseases; Acneiform Eruptions; Sebaceous Gland Diseases; Skin and Connective Tissue Diseases; Acne Vulgaris
• Other Study ID Numbers: LL-KY-2025172-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No