ViromeFlowX: Genomic and Functional Heterogeneity of Cutibacterium Acnes in Skin Microecology

Abstract

In recent years, a series of studies have underscored the intricate link between human microorganisms spanning the gut, skin, oral, and reproductive tracts and the emergence and progression of a myriad of diseases. This has broadened our perspectives and avenues for therapeutic approaches. Metagenomic sequencing has become a pivotal method for uncovering the microorganisms' role in diseases, with the efficient analysis of microbial genome information, including viral genes, resistance genes, and metabolic functions, forming the essential foundation of such research endeavors.

The significance of viral genetic information in human health and diseases is increasingly recognized, as it influences homeostasis and disease processes by interacting with bacterial genomes. Studies have highlighted correlations between shifts in phage composition and conditions like metabolic syndrome, necrotizing enterocolitis, inflammatory bowel disease, and type two diabetes mellitus.

Cross-cohort meta-analyses have identified specific gut viral biomarkers, such as phages of Porphyromonas, Fusobacterium, and Hungatella, which are enriched in colorectal cancer patients, suggesting their potential as therapeutic targets. Johansen et al.’s research has also emphasized the impact of the gut virome on longevity by finding that centenarians exhibit a more diverse and slower-working gut virome, potentially affecting their metabolism. These studies underscore the importance of investigating viral communities within metagenomes to comprehend their effects on human health.

Previous analyses, however, were limited to bacterial genomes, neglecting the wealth of information in viral genomes. To address this, we've developed ViromeFlowX, a user-friendly Nextflow workflow that streamlines the assembly, identification, classification, and annotation of viral genomes. It offers modular execution, efficient parallel processing, error handling, and a traceable execution history, adaptable to various environments including local machines, high-performance computing systems, and cloud infrastructures, facilitating rapid pipeline development and parameter customization.

Delving deeper into the diversity of information within metagenomes, we utilized this technology to investigate the mechanisms of interaction between skin microbes and skin health. The skin microbial genome represents a semi-open microecosystem closely associated with a range of common and highly prevalent inflammatory skin conditions, such as atopic dermatitis and acne. Building upon previous research, it is well- established that Cutibacterium acnes is the most widely distributed commensal bacterium on healthy skin across various body sites from adolescence onwards. C. acnes plays a pivotal roles in maintaining skin homeostasis by bolstering the skin barrier function, regulating skin pH levels, resisting colonization by Staphylococcus aureus, and modulating both innate and adaptive immunity.

Metagenomic studies show that C. acnes presence in acne lesions is similar to that on healthy skin, but acne is characterized by reduced phylotype diversity and increased virulence factor expression, exacerbating inflammation. The role of C. acnes in skin health and disease is not fully understood, and its involvement in atopic dermatitis, where it is less abundant, remains unclear.

It is crucial to note that the interactions between the host and skin microbiota play a significant role in shaping the genome and function of C. acnes. This bacterium can utilize sebum-derived triacylglycerol for energy, leading to the secretion of short-chain fatty acids (SCFAs) and the creation of an acidic environment on the skin's surface. SCFAs also play a role in regulating the virulence and resistance of opportunistic pathogens like Staphylococcus epidermidis by inhibiting biofilm formation and restoring antibiotic sensitivity, ultimately impacting the host microecosystem and health. Therefore, it is important to gain a deeper understanding of the specific mechanisms underlying mutual interactions between C .acnes and its host at a strain level.

Based on ViromeFlowX, we have expanded our analysis to include the transcriptome and metabolome data, using the same approach. Our multi-omics analysis of 1234 different C. acnes strains from healthy individuals, eczema patients, and acne patients has provided unprecedented insights into the intricate interplay between genetic diversity and skin niches in shaping functional differences at the strain level within the C. acnes species. These findings significantly enhance our understanding of the mechanisms underlying C. acnes interactions with its host, particularly in relation to inflammatory skin diseases.

This comprehensive analysis not only deepens our knowledge but also lays the groundwork for potential clinical applications of specific C. acnes strains, offering a path towards targeted interventions for improved treatment outcomes for affected individuals.

Date of Award	31 Dec 2024
Original language	English
Awarding Institution	City University of Hong Kong
Supervisor	Lixin DONG (Supervisor)