Asian Skin Microbiome

Overview

Skin is the human body’s second-largest organ in surface area, second only to the intestines. The skin itself is colonised by a vast and diverse selection of bacteria, fungi, and viruses and are collectively referred to as the human skin microbiome. Mostly harmless, these microbes are crucial to our skin and overall health. Disruption of the skin microbiome leads to various clinical conditions such as dandruff, eczema, and psoriasis.

Microbiome diversity varies among different demographic populations depending on climate, genetics, and diet. Currently, most skin microbiome research is focused on North American and Western European populations, while knowledge about Asian skin and its microbiome is minimal. Research on the Asian skin microbiome paves the way to explore novel therapeutics that enables better treatment options and improved skin health.

Our Approach

The Asian Skin Microbiome Programme (ASMP) is jointly led by the A*STAR Skin Research Labs (A*SRL) and Genome Institute of Singapore (GIS). This programme brings together scientists, industry partners, and clinicians to investigate the Asian skin microbiome. We hope to unravel deeper insights into skin disorders in the purview of the skin microbiome. ASMP scientists are developing novel methodologies for measuring skin metabolites, identifying Asian-specific fungal resistance mechanisms, and validating metatranscriptomics technologies. This overarching microbial-based approach will enable therapeutics for skin disorders to improve skin health.

Technology Tool Kit

We are building capabilities and resources to understand the skin microbiome’s function, moving from marker gene-based taxonomic studies to whole-metagenome analyses. We will be integrating metagenomes, metabolomes, and lipidomes to define host-microbiome interactions.

ASM tools and technology

More detail

Metabolomics and Lipidomics: Metabolomics and lipidomics are key to understanding microbiome function as skin metabolites and lipid composition are defined by the skin microbiome. We are establishing capabilities to integrate skin metabolomes and lipidomes, with skin microbiome data to better understand how each impact and interact with one another.

Metatranscriptomics: We are developing robust, reproducible, and validated metatranscriptomic technologies from skin samples. This, in turn, will provide invaluable insight into the various functions of the skin microbiome.

Fungal strain-level analysis: Skin mycobiome analysis is limited by the resolution of marker gene-based approaches and a lack of eukaryotic reference genomes. We have expanded our unique reference datasets and are exploring long-read sequencing technologies for better resolution and cost-effectiveness.

Selected Theme Publications

1. Bertrand, D., Shaw, J., Kalathiyappan, M., Ng, A.H.Q., Kumar, M.S., Li, C., Dvornicic, M., Soldo, J.P., Koh, J.Y., Tong, C., Ng, O.T., Barkham, T., Young, B., Marimuthu, K., Chng, K.R., Sikic, M., Nagarajan, N., 2019. Hybrid metagenomic assembly enables high-resolution analysis of resistance determinants and mobile elements in human microbiomes. Nat Biotechnol 37, 937–944. https://doi.org/10.1038/s41587-019-0191-2

2. Li, C., Chng, K.R., Kwah, J.S., Av-Shalom, T.V., Tucker-Kellogg, L., Nagarajan, N., 2019. An expectation-maximization algorithm enables accurate ecological modeling using longitudinal microbiome sequencing data. Microbiome 7, 118. https://doi.org/10.1186/s40168-019-0729-z

Functional Skin Microbiome

We hope to define the skin microbiome in healthy human skin, learn how perturbations alter skin homeostasis, investigate healthy cohorts with data on puberty, adult health, menopause, and targeted interventions. The health focus is unique, drawing strength from analysis on multiple dimensions.

ASM functional skin microbiome

More detail

Defining skin microbiome function: We have collected skin physiology, health state, consumer-relevant skin health data, metabolite, lipid, and microbiome samples from multiple body sites. We are using this metagenomics, metabolomics, and lipidomic data to generate functional information. To enable further functionalization, we have collected and are investigating a series of locally isolated microbial strains to define Singapore's microbial strain diversity.

Investigating Natural Life Changes: Puberty and menopause are critical biological phases where hormonal changes impact skin physiology and disease predisposition. We collect data from subjects in these vital phases of life and sample individuals poised for these hormonal skin and microbial changes. We hypothesize that the microbial community will change due to sebaceous gland activity and hormonal changes, which we will capture through lipidomic and blood hormone analyses.

Probing with interventions: We are -studying the skin fungal community's targeted removal using Pyrithione Zinc (ZPT), a common anti-fungal ingredient in many consumer care products. These studies shed light on how the fungal community contributes to skin cytokine signalling and "talks" with the immune system.

Selected Theme Publications

1. Leong, C., Wang, J., Toi, M.J., Lam, Y.I., Goh, J.P., Lee, S.M., Dawson, T.L., 2021. Effect of zinc pyrithione shampoo treatment on skin commensal Malassezia. Medical Mycology 59, 210–213. https://doi.org/10.1093/mmy/myaa068

2. Ambaw, Y.A., Pagac, M.P., Irudayaswamy, A.S., Raida, M., Bendt, A.K., Torta, F.T., Wenk, M.R., Dawson, T.L., 2021. Host/Malassezia Interaction: A Quantitative, Non-Invasive Method Profiling Oxylipin Production Associates Human Skin Eicosanoids with Malassezia. Metabolites 11, 700. https://doi.org/10.3390/metabo11100700

Skin Microbiome Model

We are building experimentally validated skin microbiome models with increasing levels of complexity to study “cause and consequence” relationships between the host and the microbiome. Understanding skin homeostasis and enabling the testing of various intervention strategies is key to utilizing the human profiling data that we generate.

ASM skin microbiome model

More detail

Culture conditions and microbial metabolism: We are developing polymicrobial cultures to model the skin microbiome reproducibly. Conditions are systematically varied to study their impact on the in vitro community.  Microbial cultures are used in combination with our reconstructed human skin model to mimic body’s microenvironments. This allows us to investigate clinical and consumer-relevant states such as malodour, dry/oily, or inflamed skin.

In vitro models using skin tissue-like materials: As an intermediate between pure microbial cultures and living co-cultures, we are developing models based on minimal nutrients to more naturally mimic skin surface and support microbial cultures. The simplicity of such models provides a useful intermediate for screening microbiome responses.

Living skin co-culture models: We use reconstructed skin models with specific alterations to mimic target skin conditions cultured with microbes or basic microbial communities to study host-microbe interactions. These living skin models provide a means for analytical investigations into host-microbe interactions.

Selected Theme Publications

1. Tay, A.S.L., Li, C., Nandi, T., Chng, K.R., Andiappan, A.K., Mettu, V.S., de Cevins, C., Ravikrishnan, A., Dutertre, C.-A., Wong, X.F.C.C., Ng, A.H.Q., Matta, S.A., Ginhoux, F., Rötzschke, O., Chew, F.T., Tang, M.B.Y., Yew, Y.W., Nagarajan, N., Common, J.E.A., 2021. Atopic dermatitis microbiomes stratify into ecologic dermotypes enabling microbial virulence and disease severity. Journal of Allergy and Clinical Immunology 147, 1329–1340. https://doi.org/10.1016/j.jaci.2020.09.031

2. Vijaya Chandra, S.H., Srinivas, R., Dawson, T.L., Common, J.E., 2021. Cutaneous Malassezia: Commensal, Pathogen, or Protector? Front. Cell. Infect. Microbiol. 10, 614446.
https://doi.org/10.3389/fcimb.2020.614446

Contact us

For more information on the Asian Skin Microbiome Programme, please contact Thomas Dawson, John Common or Niranjan Nagarajan (from GIS).

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