Chronic wound microbiomes: complex communities shaped by microbe-microbe and host-microbe interactions which influence healing outcomes

Date
2023-05
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Abstract

The wound microbiome refers to a collection of microorganisms, primarily bacteria and fungi, which colonize wounds, form biofilm, and cause harmful infection. Recognition of these infectious microbial communities and their role in delayed wound healing has led to increased research efforts in understanding how to model the complex interactions between multiple infecting species, understanding how various ecological factors can contribute to different types of microbes establishing infectious communities, and understanding the role of the microbiome in wound healing. To model complex polymicrobial communities, it was hypothesized that microbial communities could be isolated from patient wound infections, cryogenically preserved, and then transferred to a surgical model to replicate patient infections for study. It was discovered that the transfer of complex communities tended to disrupt bacterial profiles regardless of cryopreservation and only relatively simple communities dominated by fastidious pathogens could be readily transferred. Following this, research focused instead on the hypothesis that human genetics and climatological variation act as selective factors exogenous to the wound microbiome. Concerning genetics, a set of paired bacterial sequence profiles from wounds and human genomes were compared to discover a novel association between wound microbiome diversity and genomic loci. The primary genetic locus with the greatest association was located within an intronic region of TLN2, which encodes a protein with functions related to wound healing and the loci of interest was found to be related to alternative transcription in TLN2. Moreover, wound diversity and additionally linked bacterial species were discovered to be associated with wound healing prognosis. In the last major component, a large scale retrospective analysis was conducted for wound specimens submitted for bacterial and fungal sequencing from 43 states and over nearly 2 years. The composition of these 9,241 samples was summarized into six discrete community types, which were found to be differentially abundant across patient demographic factors such as sex and wound location. Moreover, these types explained considerable variation in the diversity of bacteria, bacterial load, proportion of anaerobes detected, and even fungal positivity. Lastly, it was discovered that climatological variation in temperature, humidity, and wind was associated with the likelihood of encountering different types of wound microbiomes. Work presented here thus describes previously unrecognized factors, genetics and climate, as being potentially important risk factors for wound microbiome composition, which is related to chronic wound healing.


Embargo status: Restricted until 06/2024. To request the author grant access, click on the PDF link to the left.

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Keywords
infection, chronic wound, genome wide association study, patient genetics, wound microbiome
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