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Study Points to Genetic, Environmental Interactions for Acne-Related Microbe

NEW YORK – New research suggests genomic features in the acne vulgaris-related bacterial species Cutibacterium acnes can vary by body site and in relation to the presence or absence of specific skin conditions, including acne or atopic dermatitis (AD), apparently reflecting distinct selective pressures imposed by different skin environments.

Past studies have linked C. acnes to everything from skin barrier function to protection against pathogenic bacteria such as Staphylococcus aureus, the investigators noted. In contrast, they explained, acne lesions tend to contain C. acnes representatives with lower-than-usual diversity and an uptick in inflammation-linked virulence factors.

"C. acnes is primarily known for its pathogenic involvement in acne, and recent studies have demonstrated its protective role in normal skin and AD. Therefore, the roles of C. acnes are far more complicated than previously thought," co-senior and co-corresponding authors Xu Yao, at the Chinese Academy of Medical Sciences and Peking Union Medical College, Wei Li, a researcher at Fudan University, Lixin Dong, with the University of Hong Kong, and their colleagues wrote in a Cell Host & Microbe study published on Wednesday.

Because skin environment features, such as the oily sebum produced by the sebaceous glands, are thought to influence the skin microbiome's C. acnes content, the investigators performed whole-genome sequencing on 1,234 C. acnes isolates obtained from 11 individuals with moderate forms of acne, 10 individuals with moderate to severe AD, and 11 apparently healthy individuals, comparing genomic features found within and across C. acnes strains in the collection.

The isolates came from several samples per participant. In the control individuals, for example, the team collected swabs at dry, moist, and oily skin sites on the forearm, inside elbow, and face, respectively, as well as samples from the plantar sole of the foot.

Along with RNA sequences and non-targeted liquid chromatography-mass spectrometry-based metabolomic profiles from the same samples, the researchers explained, the genome sequence data highlighted ties between C. acnes genome features, functional capabilities, selective pressures, transcriptomic features, metabolomic patterns, and skin environment features.

The team found that genomic features found in C. acnes isolates varied depending on the skin conditions considered and in relation to the body site sampled — differences that appeared to reflect distinct selective pressures in the bug's environment as well as C. acnes gene swapping achieved by horizontal gene transfer.

"The observed heterogeneity underscores the need for further research to elucidate the causal relationships between C. acnes strain-level genetic and functional differences and disease occurrence or severity," the authors suggested. "Gaining a deeper understanding of the intricate relationship between the host and skin microbiota holds promise for finding targets to enhance skin health and improve the management of skin diseases."

When they compared the C. acnes genomes to sequences from Staphylococcus epidermidis, the investigators saw relatively stable genome sequences containing fewer virulence factors and antibiotic resistance genes in the C. acnes isolates. On the other hand, the C. acnes genomes tended to contain more sequences stemming from pathways involved in proline metabolism and beta oxidation compared to S. epidermidis.

The team's follow-up keratinocyte cell line experiments suggested the presence of supernatant from C. acnes grown in sebum had toxic effects on the cells and prompted the expression of keratinocyte genes that promote inflammation — results that lined up with predictions from the transcriptomic analyses. In contrast, findings from metabolomic and mouse model experiments indicated that the microbes can produce enhanced levels of the oxidative stress metabolite L-carnosine to help alleviate such skin inflammation in the presence of AD.

"Whether the anti-inflammatory effect of C. acnes is a general effect in all inflammatory skin diseases needs further experimental verification," the authors wrote. "However, these results highlight that an appropriate sebum concentration and abundance of C. acnes may be the prerequisites for its protective effect."

Together, they explained, the new study "uncovered the joint impact of genetic factors and microenvironment on the function of C. acnes."