Dataset Information

Novel methodologies for host-microbe interactions and microbiome-targeted therapeutics in 3D organotypic skin models.

ABSTRACT:

Background

Following descriptive studies on skin microbiota in health and disease, mechanistic studies on the interplay between skin and microbes are on the rise, for which experimental models are in great demand. Here, we present a novel methodology for microbial colonization of organotypic skin and analysis thereof.

Results

An inoculation device ensured a standardized application area on the stratum corneum and a homogenous distribution of bacteria, while preventing infection of the basolateral culture medium even during prolonged culture periods for up to 2 weeks at a specific culture temperature and humidity. Hereby, host-microbe interactions and antibiotic interventions could be studied, revealing diverse host responses to various skin-related bacteria and pathogens.

Conclusions

Our methodology is easily transferable to a wide variety of organotypic skin or mucosal models and different microbes at every cell culture facility at low costs. We envision that this study will kick-start skin microbiome studies using human organotypic skin cultures, providing a powerful alternative to experimental animal models in pre-clinical research. Video Abstract.

SUBMITTER: Rikken G

PROVIDER: S-EPMC10580606 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Novel methodologies for host-microbe interactions and microbiome-targeted therapeutics in 3D organotypic skin models.

Rikken Gijs G Meesters Luca D LD Jansen Patrick A M PAM Rodijk-Olthuis Diana D van Vlijmen-Willems Ivonne M J J IMJJ Niehues Hanna H Smits Jos P H JPH Oláh Peter P Homey Bernhard B Schalkwijk Joost J Zeeuwen Patrick L J M PLJM van den Bogaard Ellen H EH

Microbiome 20231017 1

<h4>Background</h4>Following descriptive studies on skin microbiota in health and disease, mechanistic studies on the interplay between skin and microbes are on the rise, for which experimental models are in great demand. Here, we present a novel methodology for microbial colonization of organotypic skin and analysis thereof.<h4>Results</h4>An inoculation device ensured a standardized application area on the stratum corneum and a homogenous distribution of bacteria, while preventing infection of ...[more]

PMID: 37849006

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Project description:BackgroundPsoriasis (Pso) is a chronic inflammatory skin disease that poses both physical and psychological challenges. Dysbiosis of the skin microbiome has been implicated in Pso, yet a comprehensive multi-omics analysis of host-microbe interactions is still lacking. To bridge this gap, we conducted an exploratory study by adopting the integrated approach that combines whole metagenomic shotgun sequencing with skin transcriptomics.MethodsThis was a cross-sectional study, adult patients with plaque-type Psoriasis (Pso) and healthy volunteers were included. Skin microbiota samples and biopsies were collected from both lesional and non-lesional skin areas on the lower back. Weighted Gene Correlation Network Analysis (WGCNA) was employed for co-expression network analysis, and cell deconvolution was conducted to estimate cell fractions. Taxonomic and functional features of the microbiome were identified using whole metagenomic shotgun sequencing. Association between host genes and microbes was analyzed using Spearman correlation.FindingsHost anti-viral responses and interferon-related networks were identified and correlated with the severity of psoriasis. The skin microbiome showed a greater prevalence of Corynebacterium simulans in the PASI severe-moderate groups, which correlated with interferon-induced host genes. Two distinct psoriatic clusters with varying disease severities were identified. Variations in the expression of cell apoptosis-associated antimicrobial peptides (AMPs) and microbial aerobic respiration I pathway may partly account for these differences in disease severity.InterpretationOur multi-omics analysis revealed for the first time anti-viral responses and the presence of C. simulans associated with psoriasis severity. It also identified two psoriatic subtypes with distinct AMP and metabolic pathway expression. Our study provides new insights into understanding the host-microbe interaction in psoriasis and lays the groundwork for developing subtype-specific strategies for managing this chronic skin disease.FundingThe research has received funding from the FP7 (MAARS-Grant 261366) and the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 821511 (BIOMAP). The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This publication reflects only the author's view and the JU is not responsible for any use that may be made of the information it contains. GAM was supported by a scholarship provided by CAPES-PRINT, financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES (Brazilian Government Agency). The authors thank all patients who participated in our study.

Dataset Information

Novel methodologies for host-microbe interactions and microbiome-targeted therapeutics in 3D organotypic skin models.

Background

Results

Conclusions

Publications

Novel methodologies for host-microbe interactions and microbiome-targeted therapeutics in 3D organotypic skin models.

Similar Datasets

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