What are the changes seen in the microbiomes of healthcare workers?

I have a question!

What are the changes seen in the microbiomes of healthcare workers?

Introduction

We are taught from childhood to wash our hands after playing outside, before eating food or after we go to the loo. In healthcare we are taught to wash our hands at ‘the five points of contact’; before patient contact, before doing any aseptic procedures, after any exposure to body fluids e.g blood, after patient contact or after touching patient surroundings by the bedside etc.

This means we wash our hands a lot!

This is all in an effort to prevent the spread of bacteria to limit the possibility of healthcare associated infection. The association between hand hygiene and health outcomes of patients has been widely recognised since the implementation of hand hygiene guidelines in the ’80s. The initial link was made in the mid-1880s by Ignaz Semmelweiss who noted that new mothers had worse outcomes when treated by doctors who had recently performed autopsies or visited sick patients. Semmelweiss promoted handwashing with a chlorinated lime solution and saw maternal mortality rates fall.

Nowadays, we use hand soap and water on the hospital wards, as well as alcohol gel and other products with disinfecting ingredients such as chlorhexidine. When scrubbing in for theatres there are chlorhexidine based soaps or an iodine containing alternative that stains the skin on your hands and fingers (really useful for knowing that you have covered all the right areas!) In fact, when scrubbing in to operate, surgeons will scrub their hands at least three times to eliminate as much bacteria on the skin surface as possible.

Hospitals treat a wide variety of patients, from those with infections such as pneumonia to gastroenteritis, to patients who are severely immunocompromised, children and elderly, men and women – it makes sense to prevent transfer of bacteria between these groups. A child who comes in with a cold might carry a virus that can overcome the immune defences of an elderly patient, while a bacterial species that we all carry on our hands (E.g. staphylococcus aureus) can easily infect a wound or cannula site, leading to pain,swelling and even dangerous spread of the infection into the blood (septicaemia).

An example of a bacteria that has gained access into a tissue. Not desirable! Credits here

The benefits to the patient are clearly sensible – a reduction in microbial transfer and infection risk. Hand hygiene with chlorhexidine can almost completely reduce microbial load of specific pathogens such as klebsiella. There are good reasons that the World Health Organisation instigated the 5 moments of hand hygiene. But, especially if you’ve read my previous blog post, we know that bacteria can also be beneficial to us as part of the environment of our wider microbiome. What are the effects of all this hand washing on the healthcare professional?


We have bacteria on our skin?!

We all have skin ‘flora’. Our flora is composed of differing quantities of many bacteria, a patchwork quilt comprising organisms that arise and thrive naturally on the skin surface. There are also viruses and fungi. These microbes can be helpful, with roles from regulating skin pH to teaching our immune system to recognise good from bad. Within the mix of microbes there are species that can cause disease, or ‘pathogenic’ bacteria, but the nature of the quilt is that it is so tightly woven that good and bad species regulate each other to maintain homeostasis.

How do we get rid of these microbes?

Medical handwashing products are designed to remove visible dirt and invisible microbes. They emulsify oils on the skin, like washing up liquid does to greasy plates, to allow the oils to more easily wash away with water. They loosen the ‘biofilms’ constructed by bacteria. Some products, such as hand gels, might contain chemical substances like alcohol or chlorhexidine to leave a persisting antimicrobial layer on the skin.

Despite this engineering, because of the individual nature of our microbiomes, we cannot really know which microbes we as individuals are removing from our skin. We can expect that the total amount of bacteria is reduced, which we could think of as thinning of the patchwork quilt. We could also assume that the composition of bacteria is changed, where we lose certain patches or strands in the quilt. This means that we lose bad bacteria, but we also lose good bacteria. The balance of bacteria on the skin is disrupted, causing a change in the skin ecosystem, stretching apart the densely woven quilt into one that is weakened by holes.

In other areas of medicine, removal of flora can be disastrous for patients. If the quilt analogy isn’t working for you, think of your flora as a flower bed. Treatment with antibiotics such as ciprofloxacin can severely deplete the preexisting flora of the gut, destroying the flower bed of bacteria and biofilms that lines the gut epithelial surface. When this flower bed is thinned out it can allow the growth of a weed, a bacterial species called C. difficile. After a storm brought by an antibiotic such as ciprofloxacin, the flower bed is torn up and C.difficile, presented with a new ecological niche, has an opportunity to colonise the vacancies left by its neighbours.

C. difficile can be present in a normal well populated gut without pathological effect – it is present in small amounts in a fraction of the healthy population. Colonisation with C. difficile, however, can lead to severe inflammation of the gut wall, but more commonly to vomiting and diarrhoea, which in susceptible patients can lead to dehydration, kidney and heart failure, and mortality. We can treat C. difficile infection by giving another antibiotic, Vancomycin, which attempts to remove but also further damages the co-existing bacteria. An alternative treatment is to replace the damaged flower bed with a healthy one, achieved successfully by faecal transplantion from healthy donors.

Growing C. difficile from a stool sample on an agar plate. Credit here.

What was the question, Rory?

I am concerned that by decontaminating the skin so thoroughly and frequently throughout the days, weeks and years of a medical career, we cause short and long term changes to the skin microbiome. Although not as devastating in an acute sense as a C.difficile infection, by intending to be sterile and independent from our bacterial passengers we compromise the complex host-microbiome relationship.

Questions:

What are the microbiome-associated changes in healthcare workers (HCW)?

Perhaps healthcare professionals have a completely different composition of skin flora on their hands compared to Joe Normal of the population?

What are the changes to the skin microbiome of HCW?

What about changes to the gut microbiome of HCW?

What could the sequelae be predicted to be with regards to chronic inflammatory diseases?

Is the healthcare-associated microbiome an occupational hazard, similar to shift working?


What are changes might we see in the skin microbiomes of HCW?

This study assessed the effects of hand hygiene on the total microbial diversity in addition to the presence of four species that are common pathogens (S. aureus, Methicillin Resistant Staph Aureus (MRSA), Enterococcus and a yeast, C. Albicans). They studied healthcare workers, assumed to be nurses, in an Intensive Care Unit.

  • The nurses had pathogenic species on their hands despite soap and alcohol gel usage, with up to 52.9% having S. aureus, 5.9% having (MRSA), up to 61.8% having Enterococcus and up to 8.8% having C. Albicans.
  • HCW with reduced diversity of microbes on their hands were more likely to have pathogenic species.
  • The presence of a pathogen was associated with a reduced diversity of bacteria.
  • Washing hands often (>40) affected the diversity of microbial species on the nurses’ hands.
  • The bad bacteria persisted on the hands despite being washed >40 times, which suggested to the authors that these pathogens had colonised the skin to become long-term residents, rather than passing by transiently.
  • Older HCWs were more likely to have a greater proportion of enterococci than their younger colleagues – which may suggest that the microbiome changes over time to include the presence of pathogens. Whether this is due to ageing, due to repeated exposure to the clinical environment or to any other factors, is unknown.

So do HCWs have a different composition of flora on their hands?

The above study tells us that HCWs do carry pathogenic species on their hands. It is however probable that all humans have Enterococcus, C. albicans and S. aureus regardless of occupation, but this study does not compare against the normal population. I would hazard that because of the nurse’s reduced microbial diversity (depleting the flower bed), and the association between reduced diversity and presence of pathogenic species, the total quantity and proportions of these pathogens is different from non-healthcare workers. Perhaps if we sampled the hand microbiomes of patients entering the ICU we could tell a difference.

Caveat: Yes this was only one study but it provides preliminary answers. And more questions.

Could the healthcare environment change the microbiome of our gut?

The gut microbiome is a patchwork quilt or flower bed that comprises the bacterial, fungal and viral species, similar to that on our skin, but lining the digestive system. We are only recently discovering how significant this flowerbed is for our present and future health and disease. I watched this video about the microbiome in health and disease from the IHMC, where Dr Claire Fraser demonstrates microbiome research in general human populations – but when trying to explore my question further, trying to find studies of gut microbiomes in healthcare workers, I was unsuccessful. The research on this specific population isn’t there yet.

Microbes are present on all surfaces we come into contact with. As the above study of HCWs demonstrated, we know that our hand skin flora is sensitive to our environmental exposures. Our hands then touch our clothes, or hold that apple we eat at lunchtime, or to use our mobile phones that we glance at throughout the day. The bacteria, fungi and viruses on our hands transfer to other objects, just as naturally as people getting on and off a bus. These organisms transfer from other objects to us also. We do not live in an aseptic world, despite our efforts of hospital sterility. It is inevitable that we contact, consume and are colonised by the microbiomes of our environments.

How could a HCW-associated microbiome be assessed against long-term health outcomes?

Keep your eyes peeled for a longitudinal study comparing the data of a large cohort of ‘preclinical’ medical students who have their gut microbiomes sequenced prior to starting their ‘clinical’ study on the hospital wards. Their gut flora can be sampled regularly as they wash their hands more and more, throughout their three ‘clinical’ years. This data could be used to plot against long-term health outcomes – where simplistically, ‘HCW microbiome profile A’ is associated with health outcome A, or presence of species B is associated with disease B.

To add further value, our population of medical students could be compared against their identical twins who chose to study a non-medical subject, who would serve as the control group, highlighting further any specificity of the HCW microbiome versus the general population.

We could also analyse variance within the population of medical students, comparing groups of medical students who studied at different hospitals. The microbiome of the hospital environment is being explored by the ‘Hospital Microbiome Project’, which aims to understand the effects of medical practices (e.g. cleaning, sterilisation, antibiotic use etc) on the composition of microbiomes in different hospitals – differences that I imagine would confer different gut microbiomes in the individuals working in them.

Sounds like a difficult study!

The gut microbiome influences our body in many ways, from disease to body composition.

There is so much information about the microbiome out there so I don’t want to repeat the point that the microbiome has important roles in the development of health and disease. There are a number of really interesting, wide ranging reviews in the literature to look at. What I do have is a bunch of more questions…

We know that our gut microbiome influences the risk of inflammatory diseases.

If the healthcare worker’s microbiome can be expected to be different to Joe Normal’s microbiome, can we expect a different risk of inflammatory disease?

This BMJ ‘State of the Art Review’ review highlights the role of gut microbiota in systemic inflammatory diseases, such as Inflammatory Bowel Disease (IBD), Rheumatoid and Psoriatic Arthritis, and others.

To condense the review, many of these inflammatory diseases share the state of ‘dysbiosis’, where there is a negatively altered composition of microbes. For example, the microbiomes of people with Inflammatory Bowel Disease favour species called ‘Bacteroides’ and ‘Enterobacteria’ while having fewer species such as ‘Firmicutes’. Similar dysbiotic changes in microbiome composition are also seen in inflammatory arthropathies such as Rheumatoid Arthritis, Spondyloarthritis and Psoriatic Arthritis, although the microbial changes differ on a disease specific basis.

A commonality within these dysbioses is the reduction in short chain fatty acid (SCFA) producing bacteria. SCFAs are produced when these bacteria metabolise dietary fibres to provide energy for themselves. These fibres are indigestible to us, however, through the action of these bacteria to produce fatty acids we can derive benefits. The SCFAs act in the gut as an energy supply to the cells in the gut lining, called ‘enterocytes’. Furthermore, SCFAs move into the body to have wider influences via the human immune system. These fatty acids can upregulate ‘T-regs’, immune cells that modulate the immune response to infection or inflammation. These cells dampen down our immune system to prevent excessive immune-mediated tissue damage in circumstances of infection – where it is desirable that the immune system removes the pathogen causing disease, but undesirable that the immune system damages our own tissues!

As an example of how far these effects can be felt, SCFAs produced in the gut can also suppress inflammation in the lung. This holds relevance to the management of airway inflammation in atopic/allergic asthma or Chronic Obstructive Pulmonary Disease (COPD). Can the gut microbiota modulate lung inflammation over a lifetime to prevent or contribute to the development of chronic airways disease?

Perhaps the HCW microbiome makes us fatter.

I see a lot of increased waistlines in people in the healthcare setting (and everywhere, actually). Sure, this is compounded by the poor availability of good food versus the good availability of poor food, artificial light, stress, shift work and altered sleeping patterns, which makes finding absolute causations impossible. This concession made, our gut microbes do play a role in metabolic health and body composition. This function is (again) centred around the production of SCFAs. A SCFA called butyrate is anti-inflammatory and might prevent colon cancer, while another named acetate is thought to affect central appetite regulation to reduce diet-induced obesity through mechanisms we don’t quite get yet.

What about further applications of the HCW microbiome to health and disease?

The same BMJ review highlighted questions (below) relevant to the general population. These questions could be applied to any niche population, but seem incredibly relevant to that of HCWs.

  • Would local manipulation of intestinal microbiota affect clinical outcomes of systemic autoimmune disease?
  • Is there a “window of opportunity” for intervention to alter the intestinal microbiome to prevent or delay the onset of systemic inflammatory disease?
  • What are the potential unanticipated health effects of modifying the intestinal microbial community, such as the ability to respond to specific pathogens?
  • Further understanding the interaction of non-bacterial communities (eg, fungal, viral) with the host intestinal bacteria and immune system
  • What are the effects of the intestinal microbiota on immunomodulatory drug metabolism and therapeutic outcomes?

I often hear the aphorism ‘Genetics load the gun. Environment pulls the trigger‘.

The hospital environment may or may not affect HCWs microbiomes. I expect it does, but to an unknown level of effect. Any role that these microbiome changes have should not be seen as terminal events. The role of the microbiome just adds another bullet into the chamber of the gun of disease risk; to be added to sleep, stress, diet, physical activity etc.

Appreciating the presence of the microbiome in this specific environment does provide an opportunity for further study, understanding and potential manipulation, but this opportunity will be taken over decades. There are not any answers currently, however, if you also are an individual exposed to healthcare environments, we can do our bit on the side to modulate our microbiomes – getting outside on our days off to get exposure to a more ‘natural’ microbiota, and by eating a diet with whole foods to promote SCFA production in the gut.

One of my favourite ways to get outdoors to have fun and to exercise (with the added potential benefit of repopulating the microbiome with sources external to the hospital). Just watch out for cow poo. 

Conclusion

It is important to remember why we have stringent hand cleaning practices. We want to reduce microbial load to prevent transfer of potential pathogens to those who are currently sick or immunocompromised. From what we know, we are effective at this and by reducing healthcare-associated infections we are providing better care for our patients. We prevent further complications, speed recovery and hopefully reduce our patients’ time in hospital, accelerating their return to normal lives.

An area we haven’t studied so much is the effect of this hand hygiene on the long term microbial composition of the skin of the hands of healthcare workers. The downstream effects of this can only be hypothesised, but there is a risk that the effects are not benign and are currently overlooked. Altered skin flora can be linked to a wide variety of complaints from dermatitis to skin autoimmune conditions, while the flora in the gut and elsewhere have links to systemic inflammatory disease and chronic illness.

There is a benefit:risk ratio of everything we do in healthcare. Usually this ratio is focussed on the patient – does this treatment have a significantly higher chance of improving versus risk of worsening outcomes? We are now more frequently including logistics and economics in the equation – is the financial or logistical cost of a treatment worth the risk:benefit ratio it provides? Perhaps the effects of our antimicrobial interventions on the health of our serving population of healthcare workers should one day be included into the calculus of logistics and economics.

I find the microbiome fascinating. It adds another unseen layer to our interaction with the world in which we live. It adds complexity to the physical environment in which we work and socialise, to the food we eat, and contributes to whether we age in health or disease. It is everywhere, becoming more recognised but far from being understood. I am looking forward to seeing how the hidden world of the microbiome is uncovered with future research.

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