Microbiome-Based Therapeutics for the Skin
Microbiome-Based Therapeutics for Skin
The skin is the human body’s largest organ, colonized by a diverse milieu of microorganisms, including both aerobic bacteria (staphylococci and streptococci) and anaerobic bacteria (propionibacteria), which are directly involved in several severe skin diseases such as psoriasis, atopic dermatitis and acne. This session explores methods of understanding the skin microbiome, treating skin diseases with live and/or engineered bacteria, as well as managing skin microbiome projects.
The Skin Microbiome and Related Diseases
By Lorenzo Drago, Professor of Clinical Microbiology at University of Milan
The human skin harbors a complex microbiota which composition changes based on the different anatomical site. The skin microbiota is composed by both aerobic bacteria (staphylococci and streptococci) and anaerobic bacteria (propionibacteria), being directly involved in several severe skin diseases such as psoriasis, atopic dermatitis and acne. In the past Staphyloccus aureus, indeed, seemed to have a pivotal role in the progression of atopic dermatitis, but recently other microbial targets have been identified. Moreover, the high variability of skin microbiota due to lifestyle, sampling site and the kind of samples collected (swabs or skin biopsies) make the characterization of cutaneous microbiota a fascinating challenge for microbiologists. To date, metagenomic studies based on the combination of bacterial abundance and microbial networks are essential to clearly understand the specific role of cutaneous microorganisms, mainly considering a pathological condition. Psoriatic plaques, for instance, show a reduced biodiversity if compared to healthy skin and a change of microbial distribution in the microbiota, as different bacterial hubs can be observed comparing psoriatic skin to healthy one. In conclusion, system biology is a fundamental approach to characterize the skin microbiota, considering both pathological conditions and the different anatomical site under investigation.
Lorenzo Drago is Professor of Clinical Microbiology at University of Milan -Faculty of Medicine and Surgery – Dept of Biomedical Sciences for Health – Milan. Working Area Microbiology and Clinical Microbiology. Professor Drago is Directive Council Member of AMCLI and Responsible of the Microbioma Working Group in Italy. He is Past President of the International Society of Microbiota and Coordinator of WAIOT Scientific Commettee. The scientific interests are: microbiota and diseases, probiotics, antibiotics resistance and biofilm related infections.
High Resolution Metaproteomics and Bioinformatics Analyses to Decipher Microbiota Functions
By Cédric Bernarde, Head of Bioinformatics and Biology at Phylogene SA
Functional studies of the skin microbial communities and the interactions among community members and with the host are essential for understanding. Up to now, PCR and then sequencing allowed huge progress in the description of life by allowing the tracking of genes and transcripts, and have revealed the vast genetic diversity and coding capacity of the microbiotas in human. Also, a lot of new epigenetic mechanisms have been revealed which makes more complex the understanding of really occurring events in the cells. To this purpose, functional studies of the microbial communities, the interactions among community members and with the host are essential and proteins remain in charge of structure and function in the cell. The reported discrepancy between expressed functions and functional potential suggests that caution should be used before drawing functional conclusions from metagenomics and metatranscriptomics data, further supporting metaproteomics as a fundamental approach to characterize the human metabolic functions and activities. LC-MS/MS metaproteomics has benefited from advances in proteomics, PTMs and bioinformatics field, and is a promising approach to perform in-depth microbiome analysis as it simultaneously reveals both human and microbial changes. These improvements have led to a drastic increase in microbial protein identifications from 1000 proteins up to >10 000 proteins per microbiota. The limitations and challenges of metaproteomics include inadequate resolution of mass spectrometers to measure low-abundance proteins from complex microbial communities and the lack of an easy-to-use and high sensitivity metaproteomics computational workflow. However, the functional core proteins remain easily reachable and among the most impacted by external events. After bioinformatics analyses, important informations on occurring events can be described.
Cédric Bernarde is a biochemist. He made his PhD within an INSERM / Bordeaux University laboratory, on Helicobacter pyloriproteome and complexome. Then, he worked on bacterial secretion systems at the CEA Grenoble, and then at the Pasteur Institute in Paris. Next, he focused his researches on microbiotas. Particularly, he worked on the airway microbiota at the Brest University and finally on the intestinal microbiota within an INRA / Clermont Auvergne University team. Now, he is the Head of Bioinformatics and Biology at Phylogene SA, a company servicing in the omics field with a focus on microbiotas.
The Use of ‘Live’ Beneficial Lactobacilli to Treat Skin Conditions
By Ingmar Claes, Chief of Science, YUN
YUN is a Belgian biotech company that succeeded in building an innovative and unique R&D platform and technology, allowing to keep bacteria alive in water-based environments. Use of live beneficial lactobacilli provides an antibiotics alternative by impacting the skin microbiome. Specifically for acne vulgaris YUN developed a formulation with microencapsulated live bacteria for the treatment of acne. Besides the impact on the skin microbiome and reduction of specific skin pathobionts linked with acne vulgaris, clinical symptoms of all patients with mild to moderate acne improved in our clinical trial. The improvement in clinical symptoms of acne is further underlined by a post-market follow up study. With our current data, YUN believes this will initiate a new era of skin therapeutics based on microbiome modulation, and provides a new therapeutic option to reduce antibiotic use for common skin conditions, like acne.
Ingmar Claes is the head of science (CSO) at YUN. Ingmar studied bioscience engineering at the University of Leuven, graduated in 2007 and obtained a PhD in cell and gene technology in 2011. He has an expertise in the field of probiotics, its molecular mechanisms and the topical application of these beneficial bacteria to restore the human microbiome. As bioengineer and microbiologist, he feels that it is important to translate this scientific research into daily products from which people at home and the community can benefit. In the context of YUN, he is closely working together with the Department of Bioscience Engineering of the University of Antwerp, the Lab of Applied Microbiology and Biotechnology of prof. Sarah Lebeer, the Lab of Pharmaceutical Technology and Biopharmacy of prof. Filip Kiekens, prof. dr. Julien Lambert (dermatology) and dr. Gilbert Donders (gynaecology, the University Hospital of Antwerp). He has experience with leadership in multiple R&D projects and he held a managing role in YUN’s R&D projects of the Flemish Institute for the Promotion of Scientific and Technological Research in Industry (VLAIO). YUN’s current range of probiotic products and therapies were developed under his supervision.
Bugs as Drugs for the Skin: Engineering the Skin Microbiome for Novel Therapeutics
By Travis Whitfill, Chief Scientific Officer, Azitra
The skin microbiome plays a fundamental role in human health, protecting against pathogens and antigens while bolstering cutaneous immunity. Imbalances in the skin microbiome (i.e. “dysbiosis”) are highly associated with severity of skin disease, and research shows that improving the skin microbiome may be a promising approach to treating disease. Novel strategies have emerged to harness the skin microbiome to treat a plethora of diseases. Azitra is developing a platform to treat atopic dermatitis and other skin diseases using protein-secreting S. epidermidis. The team has engineered these strains to secrete various human proteins and is developing AZT-01 (filaggrin-secreting strain) for atopic dermatitis, AZT-02 (LEKTI-secreting strain), and AZT-04 (non-secreting strain) for chemotherapy-induced rashes
Travis Whitfill is the Chief Science Officer of Azitra Inc. His background began in molecular biology and biochemistry after receiving scientific training at the MD Anderson Cancer Center and Duke University. He has co-founded several biotech and healthcare startups companies, including Azitra. Mr. Whitfill’s strong background in entrepreneurship and business was recently acknowledged when he was named one of Forbes’ 30 Under 30 in 2018. He serves as a partner at Bios Partners, a healthcare-focused venture capital fund based in Texas, and as the Senior Analyst at Bios Research, which provides research services to institutional investors. He also is an Associate Research Scientist in the Department of Pediatrics at Yale University. Mr. Whitfill received degrees from Yale University (MPH) and Dallas Baptist University (BS in biology).
Handling a Skin Microbiome Project: Scientific Watch Associated with Best Practices for Sampling, Sequencing and Analysis
By G. Ahmad Khodr, Science Manager, L’Oreal Research & Innovation
Study design for skin microbiome research is multifaceted and integral to all downstream steps. Many published studies examined the biases introduced by the skin sampling methods and sample storage, controls and contamination sources, sequencing biases, and possible quantitation. The complexity of skin microbiome studies is nicely summarized in the title of the review from Kong et al’s (2017) “Performing Skin Microbiome Research: A Method to the Madness“. Thus, standardization and validation of the protocols, bio- informatics pipelines and sequencing platforms are crucial and key parameters of a successful skin microbiome analysis. This presentation will review the different biases influencing skin Microbiome metagenomic studies, such as errors introduced during sample preparation, sequencing and analysis and examples of a global validation and harmonization approaches (sequencing platforms and harmonization of the methods used for skin microbiome studies). In conclusion, a quality chart of skin microbiome projects will be proposed.
Ahmad completed his Degree in Biochemistry in Lebanon and then was selected by the International Scholarship program of the Ecole Normale Supérieure de Cachan to do a Masters in Microbiology and Biochemistry. Following the Masters, he conducted a Ph.D. research program in Microbiology and Molecular Biology at the ENS Cachan, France focusing on the regulation of virulence of Enteropathogenic E. coliby H-NS family proteins: differential regulation of LEE operons by H-NS and Ler proteins in EPEC. He then carried-out a post-Doc research program at the Pasteur Institute Paris, where I have applied Transcriptomics and Next Generation Sequencing tools to decipher virulence mechanisms of Legionella pneumophila. Recently, Ahmad joined the International Microbiology department in L’Oréal Research and Innovation as a Research Scientist/Manager where he leads an expertise working group that aims to build a microbiome evaluation toolbox in vitro and standardize/validate clinical/skin microbiome metagenomic studies and data.