Murray Brilliant: Good morning.
So, first, I'd like to mention our support for this from the Marshfield Clinic Research
Foundation, a grant from Delta Dental of Wisconsin, the CTSA from University of Wisconsin and
Marshfield Clinic called ICTR, and NHGRI, especially Ian Marpuri, who helped us organize
a budding consortium to study the oral microbiome and its relationship to the systemic health.
So the -- our goal is to establish an oral systemic health cohort that -- across multiple
institutions, and in doing so, we wanted to standardize enrollment of patients with electronic
health records, electronic dental records, and a set of standard clinical tests, standard
microbiome characterization, and also have genomic DNA plasma and serum, and this is
to advance translational medicine and dental care as well.
So among the participants in this group, they're listed here, and many of these contributed
to the standards that we have for enrolling these cohorts.
So, spoiler alert here, that the mouth is part of the body, and the microbiome needs
to be factored in for risk assessment of some of the most common and costly diseases.
And therefore, the microbiome has to be part of personalized medicine, and in order to
facilitate this, we would like to gather a set of patients with standardized recruitment
and sample collection, et cetera, to advance this field.
So, where we are at this point, is we've been talking about genetics, not so much about
the environment, trying to understand better complex diseases here, but one of the large
environmental factors has -- is the microbiome, and, in particular, the oral microbiome, and
that is also influenced by our diet and other environmental factors.
But the genetics and the environment then, of course, contribute to complex disease,
and, in particular, to type 2 diabetes, rheumatoid arthritis, and coronary artery disease.
So better understanding of this relationship will lead to enhanced predictive medicine,
and also can address health disparities, because if we think that medical care -- there are
disparities in medical care, there are even more significant disparities in dental care.
So the NIH, of course, has been fundamental in promoting research in the human microbiome
at various sites, and there are also a number of research opportunities and RFAs out on
microbiome.
If we consider the oral microbiome, and look at, you know, sort of a healthy tooth here,
and periodontitis over here, there are very large differences in the bacteria that are
in the periodontal space in these two situations.
In this case, the deeper pockets, you have anaerobic bacteria, and you have different
species, some of which have been shown to contribute to systemic disease.
And there's been many advances in understanding the species range of the oral microbiome,
and other omics that have to do with the microbiome.
So in this -- in our cohort here, on our group of interested institutions, we've had some
progress.
We've had a series of conference calls to plan this initiative.
We've -- we're organizing, then, this oral systemic health consortium with the standardized
recruitment criteria.
We've completed a Phase One pilot project at Marshfield, and we've standardized all
of these things here.
In the pilot project, we've enrolled 41 patients so far.
We've published a manuscript outlining the project.
We have planned enrollment of an additional 2,000 subjects at the Marshfield Clinic.
And Inga Peter at Mount Sinai, is about to enroll the first of 400 subjects, and, again,
all coordinated to be standardized so that we can combine any data that comes out of
this.
And those -- that includes long-term electronic medical records, electronic dental records,
host DNA, oral microbiome DNA, and other omics from the oral microbiome, plasma and serum
samples, and a series of standardized clinical tests at enrollment.
We've -- together, with all of our colleagues, we've come up with inclusion/exclusion criteria,
case definitions, and all of these other details shown here.
And this is the review that we published.
And at the Marshfield Clinic, although our -- the clinic, it has, for 90 years, been
focused on the medical health of the population of Wisconsin, we notice that there was -- there
were large numbers of our patients that were not receiving dental care.
So over the past few years, we've opened up a series of dental clinics for this underserved
population, and we have a total of eight right now, with a ninth clinic at Black River Falls
on the Ho Chunk Indian Reservation.
And this is the population that we serve.
Of the 41 individuals in the pilot project, we measure things like cholesterol, fasting
blood glucose, microalbumin, blood pressure, hs-CRP, hemoglobin A1C, et cetera.
And of the 41 individuals, 35 of them had an aberrant value for one of these tests.
And, in fact, at least one individual had five aberrant values here.
So if we look at the age and type 2 diabetes distribution just of these pilot subjects,
these are individuals who have already been diagnosed with type 2 diabetes.
But if we look at fasting glucose in type 2 diabetes in this population, we see in orange
here are the diabetes, some of which are controlled, and some of which are not controlled very
well.
You know, we see, there are significant numbers of these individuals that have a higher than
normal level of fasting glucose.
If we look at hemoglobin A1C distribution, we also see some individuals here who are
on their way to type 2 diabetes.
And we also have a large number of these folks that are -- that have higher than normal of
the high sensitivity C reactive protein, indicating that there's some inflammatory process going
on.
So I think that what this shows us is that -- and this is actually a population that
is relatively -- receives relatively good medical care at this time, and these individuals
were recruited from the dental clinic at Marshfield and at Chippewa Falls, but in some of the
more remote clinics, in particular, at Black River Falls, there are some individuals who
have never seen a dentist in their whole life.
So we think that this will greatly -- by providing dental care, it'll greatly improve the lives
of these individuals, but also it provides a great opportunity for research in terms
of better understanding how controlling the microbiome in these individuals could lead
to better health.
And, in addition, again, these very expensive and complex human disorders for which we have
some genetic predictors, I think we should be able to enhance that predictability by
understanding better the microbiome.
So, I just wanted to acknowledge a whole team at Marshfield, and also the -- my collaborators
in this burgeoning network, so thank you.
I'll stop here.
Marc Williams: Thank you, Murray.
Any questions, for Murray about the project?
Again, perfectly clear, and I'm sure that if any of you are interested in exploring
in more detail, you can contact Murray, and I'm sure that, as with all of the workgroups
here, we're always interested in attracting other people that might be interested in participating.
So -- but we are gratified to see that two of our members have actually gotten to the
point of enrolling patients in a specific project and have a paper, and I think that's
a great outcome, so thank you, Murray.
Next, we'll have Charis Eng present an update around the cancer working group.