Biological complexity: wound microbiome helps healing (Introduction)

by David Turell , Monday, December 02, 2024, 19:03 (1 day, 13 hours, 13 min. ago) @ David Turell

One bacterium is studied:

https://www.the-scientist.com/a-beneficial-bacterium-helps-wounds-heal-72382?utm_campai...

"...recently, we've appreciated that there is a wound microbiome—an entire ecosystem that colonizes wounds and can influence wound healing.”

"Highlighting this, White and her colleagues have shown that a bacterium found in chronic wounds can aid wound healing in mice.4 The results, published in Science Advances, uncover a mechanism of bacterial-driven wound repair and provide a foundation to develop microbiome-based therapies.

“'This study is unique in terms of bringing light on the good part of the chronic wound microbiome,” said Irena Pastar, who researches microbiome interactions in cutaneous disorders at the University of Miami Miller School of Medicine and was not involved in the study.

"To identify chronic wound-associated microbiota, Grice’s team swabbed diabetic foot ulcers from 100 participants and sequenced DNA from these samples. Among the bacteria abundantly present in the samples, they identified an environmental, non-pathogenic bacterium called Alcaligenes faecalis. Digging into published datasets, the team found that this bacterium was prevalent in different types of chronic wounds, such as pressure ulcers and venous leg ulcers. This prompted them to investigate the role of A. faecalis in chronic wounds.

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"Once the cells had formed a layer in the dish, the researchers introduced a thin scratch along the middle, disrupting the continuous layer of cells. They treated the system with either A. faecalis or a control solution and took photographs over time to track how quickly cells from the undisturbed side moved toward the scratch to fill the empty space. Compared to control-treated cells, A. faecalis treatment increased the rate at which keratinocytes migrate. They observed similar results when they repeated this experiment with skin cells obtained from people with diabetes, indicating that the bacterium likely influences wound healing in humans via a similar mechanism.

"To gain insights into how A. faecalis promoted keratinocyte migration, the researchers collected wounds from diabetic mice treated with A. faecalis and sequenced RNA from the tissue. Compared to untreated tissue, wounds treated with A. faecalis exhibited a decrease in expression of several genes. The genes most significantly downregulated encoded matrix metalloproteinases (MMPs), enzymes that break down the extracellular matrix of cells. Previous studies have shown that keratinocytes near the wound edge express MMPs, which helps these cells migrate towards wounds to help them heal.8 However, diabetic conditions promote excessive MMP expression, which is detrimental to wound healing.

"Immunofluorescence analyses of wound tissue from diabetic mice revealed high expression of an MMP near the wound edge, which decreased following A. faecalis­ treatment. Adding MMPs to A. faecalis-treated wounds resulted in these behaving similar to wounds not treated with the bacterium, validating that A. faecalis achieves its pro-healing properties by lowering MMPs at the wound site.

"White was excited by these unexpected findings, adding, “We didn't initially set out to find pro-healing bacteria.” These results offer a new perspective on the wound microbiome. “Most wounds end up healing, which means that not all bacterial colonization is bad. There are also some beneficial bacteria, which we can harness to have wound therapies,” said White.

“'The results show that we need to think about how to retain friendly bacteria while using less aggressive antimicrobial approaches to eliminate pathogens from the chronic wound environment,” said Pastar."

Comment: This research shows that many bacteria are working for the good. This should be remembered when the bad bacteria issue is raised in theodicy discussions.