Murray Brilliant: Good morning.
What I'm going to talk about today is our efforts to enhance our research by incorporating
data from the periodontal microbiome.
So, we all know that we're -- in personalized medicine, we take into account, of course,
genetics and also environmental exposure.
The microbiome is one of the most important environmental exposures that we have and the
oral microbiome, the periodontal microbiome, is known to be rather important in many of
the diseases that we're interested in.
So, we're building on our previous work in the Personalized Medicine Research Project,
which is the population-based biobank that we have that has over 20,000 subjects in it.
For each of these subjects, we have DNA, plasma and serum samples.
Access to electronic medical records that the Marshfield [spelled phonetically] Clinic
has pioneered and these clinical records go back an average of 30 years.
We also have the ability to recontact our subjects and this is -- we also have various
advisory boards, including community advisory group, ethics and security and also scientific
advisory board, and to add that, in terms of institutional support, this was all done
with Marshfield Clinic funds, which were literally millions of dollars to set this up.
And this population has been instrumental in many of the studies, for example, through
the eMERGE network, so a lot of our studies are funded through eMERGE.
We'd like to, as I said, we'd like to add to its utility and in doing that, we're creating
this oral and systemic health research project.
So we really would like to understand the connections between oral and systemic health.
It's interesting that, among many of our medical colleagues, that the mouth is not even considered
part of the body, so --
[laughter]
-- we think it is and we think the microbiome is very important.
There's tremendous evidence now, out there, of a mutual enhancement of periodontal disease
and diabetes, so that is, if you have diabetes, you're more at risk for periodontal disease
and if you have periodontal disease, you're at higher risk for diabetes.
Other common diseases linked to periodontal disease include heart disease, hypertension,
osteoporosis and each of these has a genetic and other environmental risk factors.
So also understanding the causes of oral diseases are important, what are the genetics of periodontal
disease and dental carries [spelled phonetically]?
What are the effects of genetics in these particular disorders and also if we take into
account diet, water source and of course this microbiome.
So, we're out to -- our goal is to understand really how improving oral health will aid
in systemic health, and that could be through comparative effectiveness, and to bring a
personalized healthcare to the dental arena.
So, the Marshfield Clinic has opened up seven dental centers, two more are planned.
We provide dental services to all counties in Wisconsin.
We employ 39 full time dentists in 2010, so over 30,000 unique dental patients, and this
year saw an additional 40,000 unique dental patients.
In our virtual data warehouse, we have currently about 190,000 medical patients and then this
70,000 dental patients.
In the past year, seen both by our medical facility and our dental facilities, we have
26,000 patients and in this past year 72 percent of our dental patients are also our medical
patients.
Just as we pioneered electronic health records, we've also done the same for electronic dental
health records and combining these two records together.
So, we're among the first in the nation to implement an integrated medical/dental electronic
health record environment.
So, in creating this research resource, we will recruit additional patients and actually
some of our dental patients are already in our Personalized Medicine Research Project,
but we intend to recruit an additional 2,000 patients on top of those that are in both.
In these patients, we will have, just as we do with PMRP, DNA plasma and serum, plus a
standard periodic test for fasting glucose, hemoglobin A1C, serum microalbumin and also
we will be taking samples of oral bacteria, including the periodontal microbiome.
And these individuals will also answer a detailed questionnaire on their environment and diet,
et cetera.
So we're building on previous work that we've done with our Personalized Medicine Research
Project and currently, we have about 1,500 individuals who are both dental patients and
also in PMRP and again, we're going to be recruiting two addition -- 2,000 additional
subjects.
We also have pilot projects going that are funded by the Marshfield Clinic.
Two of those are on diabetes and we've received significant funding from Delta Dental to help
in this recruitment and build this cohort.
So, like the other medical centers represented here, diabetes is one of the larger problems
that our population faces.
In our over 65 age group in Wisconsin, about 19 percent are diabetic and among all ages
adults, about 10 percent diabetic.
So, in 47,000 unique patients in which we've had both dental and medical data within our
integrated medical/dental enterprise data warehouse, we have about 9,000 moderate to
severe periodontal diseases and about 2,700 diabetic patients and we have about 1,900
diabetics who have had a dental visit within the past year, but almost 900 have not had
a dental visit.
In one of our centers, the Chippewa Falls center, these are the kinds of data that we
have currently, including tests for hemoglobin A1C, cholesterol, fasting glucose, et cetera.
So we have -- among these dental patients, we have, in just the one center, we have about
800 people who we could get data from.
What we'd like to do, among the lowest of the low-hanging fruits, without even considering
the genetic information, is to have alerts for people who have, say periodontal disease
to be screened for diabetes and vice versa.
So, this resource will combine our electronic medical record data with electronic dental
record data with genomic data and other biofluids, blood and serum samples as well as oral microbiome
samples and we hope that this will enable us to better understand the contribution of
oral bacteria to diseases.
And I'd like to refer you to a really great review that Geoff Ginsburg [spelled phonetically]
and colleagues have just published in oral diseases and I've reconstructed one of their
figures here that just illustrates how the oral microbiome can play a role in various
diseases, so.
And in answer to Teri's question, I've kind of -- I've made some notes as to some of my
colleagues here, what kinds of things that you have available and just as we've done
with PMRP, we are very open to collaborations and setting up joint research projects in
this area, so I look forward to discussing that with you later on today.
I'd be happy to answer any questions that you have.
Female Speaker: Great.
Comments for Murray?
Male Speaker: So, Murray, in your background, you've noted
the importance of environment and in the slide where you were talking about data collection,
there wasn't anything that specifically mentioned environmental factors.
I know that you do collect environmental factors for the personalized medicine program, so
the two questions I have is what is your intent in terms of collecting environmental risk
factors that may impact some of your hypotheses for this program, and the second question
is that it seems that if, in fact, there are some specific environmental factors, that
this would be a nice target for the collaboration aspect of it, presuming that the cheese level
in other collaborators may not be quite as high as Marshfield, Wisconsin, or some other
environmental factors to be named later, so could you comment a bit on that?
Murray Brilliant: Well, so I like the part about the cheese.
[laughter]
Murray Brilliant: So, [affirmative], we'll be collecting the
same environmental questionnaire data for PMRP.
These individuals -- these subjects will be within PMRP so all the data that we have on
PMRP individuals will also be collected on these new individuals as well and we've also
been working through the Fenex [spelled phonetically] collaborative to standardize a lot of these
environmental effects such as smoking and alcohol consumption and things like that.
In addition, we're gathering a lot of data in particular about water sources and fluoridation
and things like that in terms of this cohort.
And also various aspects of animal exposure and things like that that may mark our population
differently than other populations.
Yes, Pearl?
Female Speaker: Quick question.
Are you looking at the -- are you looking over time or is it a single snapshot of the
microbiome?
Murray Brilliant: Right.
Thank you.
We're going to be looking over time, so our dental patients, what we're focusing on are
kind of na久e dental patients.
Patients that, because of economics in our state and other places, are underserved, so
Wisconsin, like all other places, we have a large population of rural poor who are not
served currently for dental care, so we can actually, as these patients book at our dental
clinics, we can see, okay, they haven't seen a dentist in two, three years, something like
this.
They're also -- we also capture their health records; they're patients of the Marshfield
Clinic Medical Center as well, so we're going to focus on those na久e patients first and
collect periodontal and other microbiome specimens at their initial visit and then at follow-up
visits every six months.
So included in that are really some of the standard tests for diabetes that I've talked
about, hemoglobin A1C, microalbumin, fasting glucose, and we'll have that periodically
at six month intervals.
And that will be important in looking at effectiveness of, you know, having good dental care.
How is that going to affect their diabetic status?
Female Speaker: How are you going to characterize the microbiome?
Murray Brilliant: So, we're going to be taking samples from
four different places in the mouth, saliva, and then also more aerobic surfaces and then
anaerobic surfaces and then specimens that are associated with periodontal disease, and
then these'll be subject to 16 S [spelled phonetically] sequencing to characterize the
community.
Female Speaker: So you may be aware of the whole genome sequencing
that's already been done --
Murray Brilliant: Yes.
Yes.
Female Speaker: And that certainly gives you a lot more information.
Murray Brilliant: Yes.