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What is the goal of academic research?

We are a university-based research team led by Dr. David Relman of the Stanford University School of Medicine.To learn more about the research team, please visit our About Us page. As academic researchers, our goal is to gain knowledge, making it freely available, so that we and others can use that knowledge to develop new, effective interventions for improving health and treating disease. We invite you to participate as a volunteer in this endeavor! The not-for-profit research described on this website is funded by the National Institute of Dental and Craniofacial Research, a division of the National Institutes of Health. 

What is the purpose of this research in particular?

This page provides an overview of the three hyposalivation-related projects currently underway in the research laboratory of Dr. David Relman. 

What exactly is hyposalivation?
bottle-water-full-half-empty-three-glass-bottles-first-one-second-one-third-one-nearly-vector-illustration-45725248
The amount of saliva produced by healthy individuals varies tremendously. On average, the healthy individual, with normal salivary function, produces about 0.5 liters of saliva per day (about the amount shown in the bottle to the left). At the upper extreme, some individuals, with normal salivation, produce as much as 1.5 liters of saliva (3 times the quantity shown in the bottle or a bit less than a 2-liter bottle of soda) each day.

Individuals with hyposalivation, on the other hand, usually produce the equivalent of 1/3 the amount of saliva shown in the bottle, or less, per day. Some patients with severe hyposalivation may produce so little saliva that clinicians sometimes have a difficult time measuring their salivary flow rate using current methods.

What is the purpose of this research?
UnknownIndividuals with chronic hyposalivation, or chronically low salivary flow, experience a disproportionate number of dental cavities, as well as an atypical distribution of dental cavities. Bacteria have long been understood to play an important role in cavity formation. In our research, we aim to identify features of oral bacterial communities that distinguish states of health from the acute and chronic states of hyposalivation and the subsequent development of dental cavities. Ultimately, we hope these microbial features may serve as diagnostics, therapeutics, or prognostics.

We have three specific objectives.
1. Our first aim is to characterize oral microbial communities in human oral health.
First, we seek to identify features of microbial communities in dental plaque that are associated with states of human oral health. We feel this is a necessary first step towards identifying transition states in microbial communities that may indicate an individual’s oral ecosystem is departing from states of health. To learn more about this study, please see Understanding Human Oral Health.

2. Our second aim is to characterize the impact that acute, medication-induced hyposalivation has on human oral microbial communities.
In this study, we seek to identify features of human oral microbial communities that shift in response to the acute onset of reduced salivary flow due to the use of a medication that causes dry mouth. We hope this experiment will help us understand how taking a medication alters oral microbial communities, predisposing those who chronically take certain medications to oral disease. To learn more about this study, please see Understanding Acute Hyposalivation.

3. Our third aim is to characterize the impact that chronic hyposalivation has on oral microbial communities in patients with Sjögren’s Syndrome.
In this study, we seek to understand how microbial communities in the mouths of patients with chronically reduced salivary flow due to the progressive autoimmune disorder Sjögren’s Syndrome differ from otherwise healthy adults. To learn more about this study, please see Understanding Chronic Hyposalivation.

What causes hyposalivation? There are several causes of hyposalivation, including the use of certain medications, radiation therapy used in the treatment of certain oropharyngeal cancers, and the autoimmune disorder Sjögren’s Syndrome.

1. Medication usage is the most common cause of chronic hyposalivation. Over 400 medications are known to cause xerostomia (the feeling of dry mouth), which is a symptom of hyposalivation (reduced saliva production). MedicationsSome of the most commonly prescribed medications such as asthma medications, anti-hypertensives, anti-histamines, and psychotropic drugs may cause xerostomia. Medications generally inhibit salivary flow by blocking one of the two pathways by which salivary flow is regulated by the central nervous system.

 

 

2. A second  cause of hyposalivation is radiation therapy used to treat certradiationain oropharyngeal cancers.  Damage to the salivary glands can occur as an unintended consequence of radiation therapy during the treatment of certain oropharyngeal cancers. Radiation-induced damage to the salivary glands can be irreversible. Not all radiation therapy results in loss of salivary gland function. To learn more about radiation-induced hyposalivation, and how to manage radiation-induced hyposalivation, please refer to the American Cancer Society Website.

 

3. A third cause of hyposalivation is Sjögren’s Syndrome, one of the most prevalent autoimmune disorders in the developed world. In this progressive autoimmune disorder, immune cells impair salivary sjogrens_syndromegland function. Unfortunately, most patients are diagnosed with Sjögren’s Syndrome 6.5+ years after first experiencing dry mouth symptoms and nine years after tooth loss has occurred. We hope to improve our ability to diagnose hyposalivation and Sjögren’s Syndrome. For more information about Sjögren’s Syndrome, please refer to the Sjögren’s Syndrome Foundation Website.

 

 

What are the Consequences of Chronic Hyposalivation? We believe that some of the effects of chronic hyposalivation on oral health could be ameliorated if we better understood the pathogenesis of hyposalivation. In this section, we describe some of the common consequences of chronic hyposalivation, as well as the ways in which we hope our research will eventually abrogate some of them. 


1. Hyposalivation reduces quality of life.  
Anyone who has a fear of public speaking, and has had to give a presentation, knows how dry the mouth can feel and how uncomfortable dry mouth is – imagine experiencing that, or worse, every day! Hyposalivdry_tongueation is typically associated with a reduction in  overall quality of life because saliva has so many important functions. Saliva facilitates chewing and swallowing, as well as speaking, and it is even involved in the initial digestion of food. All of these functions may be impaired in hyposalivation.

 

2. Hyposalivation increases an individual’s risk for oral disease. Patients who have chronic hyposalivation tend to experience a higher incidence of dental disease, including dental cavities and oral mucosal infections. One reason for the increased disease risk in hyposalivation is the loss of antimicrobial agents in saliva. A second reason is that saliva promotes the remineralization of denmaxresdefaulttal enamel. A third reason is that in hyposalivation there is a decreased rate of oral clearance (i.e., reduced removal of food particles, sugars, acids from the mouth), which may provide nutrients and selective pressures leading to the growth of certain disease-associated microbes, including those associated with Oral Candidiasis. Our intention is to understand this process, so that we may develop novel therapeutics and prognostics.

 

3. The rate of cavity formation increases, and the distribution of cavities is altered in patients with severe hyposalivation.  Cavity formation typically takes years in healthy humans. However, in individuals with chronic hyposalivation, such as some patients treated with radiation therapy, cavity formation may occur on the timescale of months (especially in the absence of dentaScreen Shot 2013-12-02 at 7.21.08 PMl prophylaxis). Interestingly, in individuals with hyposalivation, cavities are frequently seen on the front teeth (the incisors and canines), sites that are typically resistant to cavities in otherwise healthy humans. We are very much interested in understanding how the microbial communities in the mouth change over time in health, as well as in the acute and chronic states of hyposalivation,  so that we may eventually prevent hyposalivation-related caries from occurring, and reduce the incidence of dental disease.

 

Why are we interested in studying microbial communities in states of hyposalivation?

Before dental cavities form, there is a disturbance in the “normal”, health-associated bacterial communities typically found in human dental plaque. Research studies have shown that reduced salivary flow restructures bacterial communities, often selecting for the growth of disease-associated bacteria, in the long term. Our purpose in this study is ultimately to identify a salivary flow rate threshold below which microbial communities can be distinguished from health-associated communities, so that we may identify microbial diagnostic and prognostic markers that are associated with states of hyposalivation but not with health or dental cavities.

To learn more about each specific research study, please go to the following links:

  1. In the Understanding Oral Health project, we  seek to understand the spatial and temporal variation of oral microbial communities in healthy adults who experience “normal” salivary flow.
  2. In the Understanding Acute Hyposalivation project, we seek to understand how an FDA-approved medication, which causes dry mouth, modulates the spatial and temporal structure of oral microbial communities.
  3. In the Understanding Chronic Hyposalivation project, we seek to understand how the spatial variation of oral microbial communities in patients with Sjögren’s Syndrome differ from the oral microbial communities of otherwise healthy adults.

Funding
nidcr_logoThis not-for-profit research project is funded by a National Institute of Dental and Craniofacial Research grant (R01-DE23113-001) to Dr. David Relman.