Our skin provides a natural barrier to the environment. This is crucial for our health, as skin protects us from invasive pathogens such as bacteria and viruses.
When the skin barrier is damaged, these pathogens are ready to make their way into the body to colonise it. This is particularly dangerous if the bacteria in question cause widespread damage to skin or other tissues, and if they are resistant to antibiotics.
Staphylococcus aureus is naturally present in the noses of around 30 per cent of the population and mostly does not cause harm. However, when the skin barrier is broken, S. aureus can cause a severe infection.
S. aureus is notorious for forming biofilms. When this happens, the bacteria attach to a surface, such as the skin, and sugar molecules form a protective matrix around the bacteria. Biofilms are mostly resistant to antibiotics and are therefore a considerable health risk.
If S. aureus spreads to the blood it can cause sepsis, which is a major cause of death in children who have experienced severe burn injuries.
Pseudomonas aeruginosa, which is another pathogen known to form biofilms, is often found in infected burn wounds. Normally resident in the gut, this pathogen invades and colonises the skin, followed by other organs such as the liver and lungs, in immunocompromised individuals such as burn patients.
Although antibiotics are used in wound treatments, multidrug resistance is common and infections persist. Scientists are searching for alternatives. Could bacteria provide much-needed strategies to prevent life-threatening infections?
Probiotic bacteria show promising potential
Do bacteria have antibacterial properties? Yes, they do; they naturally compete with each other for living space and food. To achieve this, bacteria produce antimicrobial molecules that specifically prevent the growth of other bacteria by altering the growth environment in their favour and by disrupting communication between other bacterial cells.
Catherine O’Neill, PhD, senior lecturer in the Division of Musculoskeletal and Dermatological Science at the University of Manchester in the United Kingdom, and her team have tried to harness these properties by using bacteria to prevent pathogen infections.
But does skin harbour suitable bacteria? In response to that question, Dr O’Neill told Medical News Today, “We really don’t have any idea of skin probiotics. We don’t know enough about the skin’s microbiome and how it interacts with the wound.”
Instead, she uses lactobacillus bacteria, which are a group of so-called friendly bacteria, in her research. Lactobacilli are mostly harmless and some strains are a crucial component of our daily lives in that they facilitate the fermentation of products such as yogurt, beer, and wine.
Dr O’Neill’s team showed that both L. rhamnosus GG and L. reuteri could protect skin cells in the laboratory from infection by S. aureus. This was true when live bacteria were added to the skin cells and when the bacteria were killed and their extracts added instead.
In a recent study published in the journal Scientific Reports, Dr O’Neill further showed that the two lactobacilli had different effects on skin cells in a wound healing model.
L. rhamnosus GG mostly promoted cell migration, allowing the cells to close the artificial wound rapidly, while L. reuteri increased rates of cell division, helping to replenish the pool of cells destroyed by the creation of the wound. This study used bacterial extracts rather than living cells.
Dr O’Neill told MNT that she sees bacterial extracts as a safer way to treat patients because there are incidences when lactobacillus bacteria have entered into the bloodstream of immunocompromised patients and caused harm.
“I doubt you would get any clinician to put live bacteria onto a wound [in the UK],” she explained. “We would have a lot more success getting a dead organism through ethics committees.”
From the laboratory to animal models
A handful of studies have gone further and tested the effects of probiotics in mouse models of burns and wound healing.
Susan E. Erdman, assistant director in the Division of Comparative Medicine at Massachusetts Institute of Technology in Cambridge, and her team looked at the effect of adding probiotics to the diet of mice on wound healing.
Their study, published in PLOS One, showed that feeding L. reuteri to mice resulted in an increase in oxytocin, which is a hormone important in reproduction, childbirth, lactation, and social behaviour.
Interestingly, the increase in oxytocin was accompanied by a faster rate of wound healing in older mice. Their wounds closed twice as fast as those of control mice.
In a study published in Clinical Microbiology and Infection, Juan Carlos Valdéz, PhD, from the National University in Tucumán in Argentina, and colleagues showed that L. plantarum can inhibit the growth of P. aeruginosa both in vitro and in a mouse model of burn wound healing.
Sandeep Kathju, MD, an associate professor in the Department of Plastic Surgery at the University of Pittsburgh School of Medicine in Pennsylvania, and colleagues investigated the effect of L. plantarum on P. aeruginosa-induced sepsis in a mouse burn model.
The study, published in PLOS One, showed that in 12 out of 13 mice, L. plantarum prevented sepsis and did not have any detrimental effects on burn wound healing.
But while these studies in mice are encouraging, is there any evidence in humans?
Patients improve with probiotic treatments
Dr Valdéz and colleagues performed a small study with eight patients in the Plastic Surgery and Burns Unit at Hospital Centro de Salud ”Zenón Santillán” in Tucumán, Argentina.
These patients had a mix of second- and third-degree burns, and the team found that L. plantarum was as efficient as silver sulphadiazine, a commonly used antimicrobial, in preventing and reducing burn wound infections.
Richard J. Kagan, M.D. – a professor of surgery at the University of Cincinnati College of Medicine in Ohio – and colleagues reported the results of a clinical study on paediatric burn patients in the Journal of Burn Care & Research. This study included 20 children, half of whom received a probiotic and half of whom were treated with a placebo.
The mean age of the patients was around 7 years, and the treatment was administered daily, starting 10 days after their initial burn and lasting until their wounds were closed.
The wounds of patients treated with probiotics healed at a faster rate than those of patients treated with a placebo.
Based on these studies, why are probiotics not commonplace in clinics around the world? It’s a question of numbers.
Not enough evidence yet
Baljit Dheansa – lead surgeon for burns at Queen Victoria Hospital in East Grinstead, U.K. – told MNT, “It’s interesting to hear about these probiotics but to date there has been very little robust evidence to show that they have a significant effect in general, though there are many anecdotal reports. In relation to wound healing, I think there is even more doubt.”
“If probiotics are to usefully enter the wound healing arena we need to make sure that we conduct well-constructed research studies that will help us establish a proper evidence base for their use in real wounds in humans rather than in the lab” said Dheansa
But in the face of multidrug-resistant bacteria posing a real threat to human health, alternatives to classic antibiotics are desperately needed.
In fact, P. aeruginosa is on the World Health Organization’s (WHO) list of critical pathogens for which new antibiotic treatments are urgently needed, closely followed by S. aureus, also listed as a high priority.
Dr O’Neill also commented that wound healing was a clinical area that is “desperate for some innovation,” but what is the likelihood of a commercial company investing in costly clinical trials to develop probiotics for wound healing?
Dr O’Neill thinks that “commercially it could be extremely successful,” especially as the bacterial lysates that she works with are not expensive to produce. For now, though, treatment with probiotics remains the prerogative of the physician and the healthcare setting.
In a report published in the Journal of Wound Care, Kenneth Dunn – a consultant burn and plastic surgeon at University Hospital South Manchester in the U.K. – and colleagues used a popular probiotic yogurt drink to treat a patient with extensive burn wounds and a multidrug-resistant P. aeruginosa.
The bacteria had populated both the skin and the gut, and the team thought that the gut was acting “as a reservoir for re-infection.” Within 2 weeks of treatment, the P. aeruginosa population had changed from multidrug-resistant to drug sensitive, allowing the team to successfully eradicate the patient’s infection.
With our increasing knowledge of the importance of the microbiome for health, there is a chance that bacteria – or their extracts – will one day successfully join the fight against their pathogenic cousins, thereby keeping deadly skin infections at bay.
Source: Medical News Today