Interview with microbiologist John G. Thomas, USA
Prof. John G. Thomas has been a clinical microbiologist since 1969. He is currently working at the West Virginia University in Morgantown, USA, where he also holds the position of the Director of the Clincial Research Laboratory of Microbial Patholoy, focusing on the integration of dental, medical and environment diseases through four linked pathways: biofilms antibiotic resistance, clinical and financial outcomes, and global oral hygiene. Dental Tribune Group Editor Daniel Zimmermann was able to speak to him during the IDEM show in Singapore where he gave a lecture on “Managing biofilm for optimal oral health”.
Daniel Zimmermann: Prof. Thomas, in your lecture you compared the composition of biofilms to the United Nations. This is a real interesting analogy. Can you explain that concept to our readers?
Prof. John G. Thomas: When I think of the United Nations, I like to think of it at its best scenario with a constant exchange between all members. There is a hierarchy in the United Nations, first the Council with the United States, China, Russia etc. and then the rest of the nations. The UN has a structure but everybody does contribute and theoretically every member should have equal voting rights except for the regulatory highest session.
Biofilms are exactly the same. There are a huge number of members that are equal and they do communicate. They are all important but there are a number of organisms that are clearly more important. The point that I wish to make is that communication and networking within the United Nations were it to be optimum is what really a biofilm does. It optimises communication but there is a recognized hierarchy and the final decision tree upon how well the biofilm is built is not dependent upon every member but dependent on a selected few.
How many micro organisms are actually needed to build a biofilm?
The answer to this question depends on who you read, but we say there are more than 700–900 different organisms involved.You mentioned in your lecture that there are only 10 key members out of these 900?
We have based our information on cultural methods which we recognize are rather inferior. As we expand the molecular architecture and description we will find that there are probably more than 10, but the reality is, that at my best guesstimate there are probably no more than 50 that are really the key in promoting disease. Those key members would be the ones that we should address, maintaining a reduced population of those 50, maybe 75. But the rest of the 700 are not terribly important except for the fact that they fill a void.
So, do they have an influence at all then?
They have an influence only in the fact that they represent a community and they do have the ability by mere and sheer numbers to occupy space but they are limited in what they can influence as the outcome.
How has modern microscopy changed the way we look at biofilms?
Microscopy that is really advancing us is called quantitative microscopy. It allows us to essentially look at a biofilm in a 3-D configuration. With the combination of actually using confocal laser scanning microscopy we can section the biofilm as a CAD scan and then, with sophisticated software, reassemble it. Reassembling allows us to quantify distances between organisms and spatial arrangement—the single key feature of a biofilm. Structure equals function, and the structure that is most important, is spatial arrangement. That spacing is best defined now by quantitative confocal laser scanning microscopy. The unique software that we use is a shareware on the Web, called Comstat. It defines nine physical parameters of a biofilm and those images help us to restructure what a biofilm looks like.
Looking at biofilm on these levels, what exactly do we see?
What we see are domains. Coming back to the United Nations analogy, let us think of it as a city. Within that city you have different districts that are defined by structural differences. Biofilm has the same thing but
in fact it is structurally different in each region. We call those domains because the building block is a microcolony. Microcolonies make up domains and domains make up the biofilm. The 3-D images using Comstat and confocal let us arrange the different regions within the whole biofilm community. That structure of the three sections or four domains is what makes biofilm so unique.
If we start to understand how biofilms are composed, we clearly see that there is an impact on the whole body. How so and can you give us an example?
It is amazing to me as a microbiologist of 41 years that I know a lot about the microbiology of only three out of the four microbial reservoirs, which are the gastrointestinal tract, the mouth, the urogenital and the skin. I unfortunately know very little about the mouth. But the point is, those organisms have well defined disease entities and people know that E. Coli that gets to the bladder, probably arrived from the urogenital and migrates up. But we never recognized that there is a reservoir in the mouth that has a contribution to other distant sites of the body. The microbial reservoir of the mouth can for instance cause low birth weight babies, diabetes, arterial sclerosis or pulmonary disease. And the ways in which these are manifest are a little different.
Arterial sclerosis and plaque are associated with stimulation and accumulation of white cells whereas ventilator associated pneumonia is the actual organisms from the mouth getting access to the lung. In the case of the low birth weight babies, organisms in the mouth expand their function in the urogenital tree by being genetically similar and they cause a restriction of flow to the foetus and ultimately expose to have a low birth weight baby. There are different vehicles by which the mouth flora can cause disease: maybe through immunology, maybe through the organism, but the concept now is to get recognition that the mouth is a major seed for distal sites in the body.
Does it also work the other way around?
Probably not. Clearly, the point I was trying to make is that we are walking in a microbiological world. We constantly reshuffle the pool because we are always using our hands. We also eat with our hands and therefore continually challenge the four reservoirs. But 80 per cent of those reservoirs are dependent
on age and on gender and don’t change, except with age. So we influence 20 per cent of that.
So probably 20 per cent of the organisms in the mouth are organisms from the skin or from the urogenital. So yes, there is a constant influx, but it doesn’t influence the outcome as much as you might anticipate. Organisms in those sites are fairly stable, 80 per cent.
Let me give you an example. Enterococcus faecalis is the most common recognized organism that causes endodontic failure. Where is it in the mouth? Well, you can’t find it there. It is almost never cultured out of the mouth. Enterococcus faecalis, as the name suggests, is normally located in the stool. So, how do you think it got from the stool to the mouth? The reality is we carried it there. But this is a classic example of a site influencing the mouth in a negative way. So it does happen both ways.
You also said in your lecture that all these microorganisms have to be in balance. What can dentists do to achieve this balance?
First and foremost, you have to look at the whole body. Other underlying diseases a patient may have are not going to eradicate the problems with the mouth. Firstly, dentists need to figure out what underlying diseases do the patients also have. Are they diabetic, overweight, or smokers, etc.? Secondly, what are the habits that personally address the normal flora, like oral hygiene techniques, economic status, etc. The oral hygiene techniques are what a dentist can have an impact on: the mechanical removal of the bugs, via
traditional flossing and chemical management.
I think what is going to happen is that probiotics are coming very much into the focus. They can help us establish a reservoir of good bugs because by nature itself this replenishing from distal sites of the skin to the mouth is not very efficient. So you have to reduce the underlying disease, address the primary disease,
and give a population of bugs a chance to re-establish an oral flora. And I think what is going to happen in the near future is that one, let’s get the patient off antibiotics, unless of course they are for a specific purpose. Two, let’s establish that the best treatment is no treatment and let the normal flora apply and three, recognize that things like probiotics play a part.
I was recently asked to lecture in Manchester at the British Dental Association, where I am going to address probiotics. Six months or a year ago I think the topic was relatively non-clinically applicable. I think it is now beginning to become very obvious that what we have done so far hasn’t worked, so we need some new options. I think probiotics is finding a place, although it is not the answer alone. I guess the single most important thing is that every patient needs to be addressed as an individual. You cannot find a single solution. So whether you emphasize probiotics, mouth cleaning or total body management, it has got to be tailored to the patient.
You mentioned that at your home university you bring students to the ICU, Intensive Care Unit. Should this be part of every dental curriculum?
Absolutely! I think there is
another key element here that is emerging and which I try to address. If we do not communicate with our medical colleagues and vice versa, we are never going to solve the problem. It was amazing to me that by inserting the dental students into the curriculum of the medical personal, the nurses, respiratory therapists and the doctors found, that dental students have a contribution to make. It was a great bridge building event. I can tell you that in the US they are saying, each hospital is going to be required to have
an oral care policy and I want to make it a tool by which the dental community writes a policy that the medical profession will apply.
If we start to understand how these micro organisms are working together, do you foresee many diseases or chronic conditions to be treatable in the near future?
It is becoming very apparent that biofilm is becoming the universal survival vehicle of microbes. What we are recognizing—in the diabetic, in the pressure ulcer, in the wounds distal to the mouth—is that the organisms are different but the biofilms have exactly the same structure. And what I am saying to dentists is that a periodontal pocket is a wound. They never think of it that way. Whether you have a wound on the skin or in the mouth, the biofilm is forming the same disease with a slightly different population.
However, the common denominator still continues to be Candida albicans. We find Candida in more superficial wounds and we find it periodontal pockets. So, I try to tell the medical profession, that a periodontal pocket isn’t unique to dentistry. The same recovery vehicle is seen in a distal wound. So do I see success in wounds? Not for a while because we do not understand what we see in wounds any better than what we see in the periodontal pocket. I do not see us having a good answer with these chronic infections before the next five to 10 years.
Connecting back to the patient, who is the main carrier of these micro organisms, what can be done in regards to the patient, especially in third world countries, where hygiene in general still is a problem?
Unfortunately, there is no money to make this work to the degree we would like to make it work. But I think the two main factors that we need to focus on are clean water and education. Global warming is going to have an impact on wound infections and oral care because the access to good water is going to become less easy than it has been in the past. We see that hydration is a major feature of biofilms and
if people do not have access to clean water, a whole lot of bad things will happen. Also, cleansing wounds with clean water is absolutely imperative. Additionally, we need to focus on educating people on how important good oral hygiene is, which I still think is largely underestimated.
Thank you for the interview.