Study of Skin and Gut Microbiome in a Skin Condition Involving Skin Barrier Impairment and Allergic Symptoms: Netherton Syndrome (DERMABIOTE)

It is proposed to conduct an exploratory study to analyze the skin, intestinal, and salivary microbiome, as well as the skin mycobiome and virome, of patients (adolescents and young adults) with Netherton syndrome, a condition characterized by an impaired skin barrier that most likely promotes the development of allergic manifestations.

The study will be conducted on patients with Netherton syndrome and control subjects in order to investigate possible correlation factors between the three microbiomes and identify which ones.

Study Overview

• Status: Not yet recruiting
• Conditions: Netherton Syndrome
• Intervention / Treatment: Biological: Superficial skin swabs; Biological: Superficial skin swabs; Biological: Stool samples; Biological: Saliva samples; Biological: Blood samples; Other: Data-Collection; Other: Data-Collection

Detailed Description

Netherton syndrome (NS) is a genodermatosis characterized by the combination of (i) pruritic erythematous-squamous skin lesions, often erythrodermic, with inflammatory skin flare-ups, (ii) frequent hypernatremic dehydration in the neonatal period, (iii) food allergies with increased IgE levels, and (iv) growth retardation. Autosomal recessive in transmission, it is linked to mutations in the SPINK5 gene encoding the LEKTI protein, leading to abnormalities in epithelial barriers, particularly in the skin and esophagus. Digestive disorders such as abdominal pain, chronic diarrhea, or eosinophilic digestive disorders are common, as described by the dermatology team at Necker-Enfants Malades Hospital, MAGEC center. Thus, NS is a model of a rare disease combining skin inflammation and impaired epithelial barriers. It is essential to define all therapeutic strategies that can relieve patients of what is currently a chronic, severe, and orphan disease. Currently, there is no specific treatment available. The permeability of the skin barrier means that treatment with topical corticosteroids should be avoided as much as possible. Their use therefore remains very limited.

Recent data concerning the study of the skin microbiome of patients with SN have confirmed the presence of dysbiosis and shown the over-representation of Staphylococcus aureus and epidermidis strains, as well as the harmful role of certain proteases produced or stimulated by these strains. However, these studies involved a limited number of patients (a maximum of 10 NS patients), all adults, and did not include skin sampling sites of particular interest, such as skin folds in patients with chronic vegetative cellulitis, which is rarely described but observed in some NS patients. Furthermore, although these patients frequently present with digestive disorders, the digestive microbiome has never been studied in NS. A comparison between studies of the skin and digestive microbiome in systemic inflammatory diseases such as NS throughout life remains unprecedented.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Christine BODEMER, PhD; Phone Number: +33 01 44 49 46 72; Email: christine.bodemer@aphp.fr
• Study Contact Backup: Name: Victor BRUYERE, MSc; Phone Number: +33 01 34 29 23 24; Email: victor.bruyere@aphp.fr

Study Locations

• France
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75015
      • Hôpital Necker Enfants Malades
      • Contact: Christine BODEMER, PhD; Phone Number: +33 01 44 49 46 72; Email: christine.bodemer@aphp.fr
      • Contact: Nathalia BELLON, Dr; Phone Number: +33 01 44 49 57 88; Email: nathalia.bellon@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Inclusion of children, adolescents, and young adults with Netherton syndrome, and control subjects of the same age and sex, treated at the service but without dermatosis or inflammatory and/or autoimmune diseases.

Description

Inclusion Criteria:

Group A:

• Children aged 10 years and older and adults with confirmed Netherton syndrome diagnosed at age 10 years or older (clinical and histological and/or molecular)
• Patients and legal guardians informed about the study and not opposed to participation in the study

Group B:

• Children aged 10 years and older and adults with no skin barrier impairment, dermatosis, inflammatory disease, or autoimmune disease.
• Subjects and legal guardians informed about the study and who do not object to participation in the study.

Exclusion Criteria:

• Refusal by parents/guardians, children, adolescents, or adults.
• General or local antibiotic therapy within the month preceding the consultation.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with Netherton syndrome; 15 children, adolescents, and young adults with Netherton syndrome	Biological: Superficial skin swabs; Sampling areas: (18 swabs in total + 6 swabs for routine skin mapping); Lesion area outside skin folds (e.g., back or limb); Healthy area outside skin folds (e.g., back or limb); Perioral area of the face; Scalp; Inguinal fold; Axillary fold; Biological: Superficial skin swabs; Three superficial skin swabs: same locations as for Netherton patients; Biological: Stool samples; A stool sample collected for analysis of the fecal microbiome and mycobiome.; Biological: Saliva samples; A saliva sample collected for analysis of the saliva microbiome and mycobiome.; Biological: Blood samples; For group A: cytokine profile from an additional blood sample taken during a blood draw for treatment For group B: cytokine profile if there is any residual blood sample from the treatment; Other: Data-Collection; Socio-demographic data and lifestyle habits of the patient and parents; Other: Data-Collection; Clinical data, treatment data, and results of biological tests carried out as part of routine monitoring
Control subjects; 15 control subjects of the same age group and gender, treated at the service but with no dermatosis or inflammatory and/or autoimmune diseases.	Biological: Superficial skin swabs; Sampling areas: (18 swabs in total + 6 swabs for routine skin mapping); Lesion area outside skin folds (e.g., back or limb); Healthy area outside skin folds (e.g., back or limb); Perioral area of the face; Scalp; Inguinal fold; Axillary fold; Biological: Superficial skin swabs; Three superficial skin swabs: same locations as for Netherton patients; Biological: Stool samples; A stool sample collected for analysis of the fecal microbiome and mycobiome.; Biological: Saliva samples; A saliva sample collected for analysis of the saliva microbiome and mycobiome.; Biological: Blood samples; For group A: cytokine profile from an additional blood sample taken during a blood draw for treatment For group B: cytokine profile if there is any residual blood sample from the treatment; Other: Data-Collection; Socio-demographic data and lifestyle habits of the patient and parents; Other: Data-Collection; Clinical data, treatment data, and results of biological tests carried out as part of routine monitoring

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Study of the skin, salivary and intestinal microbiota	Analyse the skin microbiome, mycobiome, and virome, as well as the intestinal and salivary microbiome of patients with Netherton syndrome in comparison with healthy controls.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in microbiome signature	Identify any changes in the microbiome signature of patients with Netherton syndrome.	Baseline
Microbial interactions of the skin	Study the relationship between the different skin microbiome, mycobiome, and virome	Baseline
Circulating cytokine profiles	Study circulating cytokine profiles	Baseline
Markers of digestive inflammation	Study markers of digestive inflammation in stool samples	Baseline
Factors influencing the microbiota	Analyze parameters that may impact the microbiotes, including various elements from these patients medical histories.	Baseline

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: URC-CIC Paris Descartes Necker Cochin

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 1, 2025
• First Submitted That Met QC Criteria: December 1, 2025
• First Posted (Estimated): December 12, 2025

Study Record Updates

• Last Update Posted (Actual): December 23, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Netherton syndrome; skin microbiome
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Infant, Newborn, Diseases; Skin Diseases; Congenital Abnormalities; Abnormalities, Multiple; Skin Diseases, Genetic; Skin Abnormalities; Keratosis; Ichthyosiform Erythroderma, Congenital; Ichthyosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Netherton Syndrome; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Blood Specimen Collection; Data Collection
• Other Study ID Numbers: APHP250480; ID-RCB Number (Other Identifier: 2025-A00978-41)

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