When dentists look inside your mouth, they’re not just looking for cavities. They look for gum disease and oral cancers, as well as assess the overall health of the millions of bacteria, fungi and viruses that live there – mostly, but not always, in harmony.
“For a long time, people thought oral health was about brushing teeth, aesthetics and bad breath. But the mouth is the main entry point between the outside world and the inside of your body,” said Margôt Bacino, Postgraduate Researcher. in the oral craniofacial sciences program at the UCSF School of Dentistry. “We need to understand how the oral microbiome works and how it affects our overall health, as there are links between oral health and many inflammation-related diseases, including Alzheimer’s disease, rheumatoid arthritis, obesity, diabetes and adverse pregnancy outcomes’.
These millions of bacteria, fungi and viruses interacting in your mouth are what healthcare providers call the oral microbiome. Bacino is one of several researchers and clinicians at the School of Dentistry studying it so they can develop new treatments and prevent disease. The oral microbiome is the second most diverse in the human body, after the gut, but relatively poorly studied—which is why researchers believe it has great potential for health advances.
“Many of the mysteries of health are waiting to be solved through the study of the oral microbiota,” he said. Michael Reddy DMD, DMSc, Dean of the School of Dentistry and Deputy Vice-Chancellor, Oral Health Affairs. “UCSF is investing in this area of research because it holds great promise for the early detection of serious diseases—not just in the mouth, but by using the oral microbiome as an indicator of health throughout the body. The links between oral disease and overall health require us to think more holistic than we were, not only in research but also in care delivery. That’s why the dentists at UCSF use the same health record as our colleagues in medicine, nursing and pharmacy, and work together to provide health care for the whole person.”
This is also why microbiome research is multidisciplinary at UCSF. THE Benioff Center for Microbiome Medicine (BCMM) at UCSF is a central home for human microbiome research across UCSF’s four schools of Medicine, Dentistry, Pharmacy, and Nursing. It supports research like Bacino’s, as well as others studying gut, skin, respiratory microbiomes, and more—along with efforts to diversify the microbiome workforce and symposia. BCMM began five years ago thanks to Marc and Lynne Benioff, and the oral microbiome research program began three years ago with a gift from Larry Berkelheimer and is expanding its research facilities on the Parnassus Heights campus with an $8 million federal award received recently.
“At BCMM, we have moved toward integrated, multidisciplinary research with a growing appreciation for the role of the oral microbiome in both oral and systemic health,” he said. Sue Leeds PhD, professor of the School of Medicine and director of the BCMM. “In addition to treating inflammatory diseases, we are also firmly focused on prevention. There are so many chronic diseases without a cure, we want to develop microbe-derived strategies to both manage and prevent these conditions.”
In the footsteps of her family
Because of its prevalence, lack of treatments, and impact on the health of other organs, a central focus of oral microbiome research is periodontitis, a severe gum infection that destroys the soft tissue around the teeth due to prevalence and lack of treatments. About 40% of US adults over the age of 30 have some level of periodontitis, which can be caused by factors such as poor oral hygiene, smoking, pregnancy and family history. That number rises to 60% for adults over age 65, according to the Centers for Disease Control (CDC).
As a member of Lynch’s lab, Bacino creates clones of E. coli bacteria that have DNA added from the oral microbiome. He has tested thousands to see if they can inhibit oral bacteria associated with periodontal disease.
“Right now, current treatments for periodontal disease rely on repeated deep cleanings often combined with antibiotics. My ultimate goal is to expand the clinics’ toolkits to better manage periodontal disease,” said Bacino, who follows in the footsteps of her grandfather, an aunt. and an uncle who are dentists. “I’m looking for certain microbes that inhibit others that are associated with periodontal disease, the ones that affect the way the whole microbiome acts and wreak havoc on someone’s oral health. It’s like when there’s a petulant child in a classroom, they make the whole class is behaving differently, I’m looking for ways to keep the class calm without removing that child – and I’m finding some possibilities that I’m starting to explore more.”
Once Bacino identifies the microbes and the specific genes that can slow their growth, she wants to turn that into a cure. “I think it’s possible to take aspects of a healthy person’s mouth and translate them into new treatments,” he said. “Depending on the microbe, maybe it could be a new probiotic that a patient takes or a new concentrated mouthwash.”
Bacino works with UCSF dentists and dental students to collect her samples. “It’s beneficial that at UCSF we have patient clinics and research labs on the same campus. The moment human mouth samples are taken, they start to change for the worse—the RNA degrades, the microbes die. I work with our clinicians to I collect the samples in a way that keeps the cells as fresh as possible, and then it’s only a 10-minute walk between the collection site and the lab, so I have a lot of control over the samples.”
Does periodontitis contribute to premature births?
Christopher Bravo’s research takes a different approach to periodontitis, investigating how the oral microbiome is associated with adverse pregnancy outcomes such as preterm birth.
“We know there is a mouth-uterus connection, and we need to understand it more, especially because it disproportionately affects minority patients,” said Bravo, also a graduate student in the oral craniofacial sciences program at the UCSF School of Dentistry and a member of Lynch’s. laboratory.
His research examines the oral bacteria that are prevalent in the early stages of infant life from the womb to the first weeks of life, especially in babies who were born prematurely or whose mothers suffered an adverse pregnancy outcome. About 40 percent of pregnant women have some form of periodontal disease, and although researchers don’t yet know why, that rate is higher among racial and ethnic minorities and women of low socioeconomic status, according to the National Institutes of Health. About 10% of babies in the US are born prematurely, before 37 weeks, and can experience a range of health problems, from breathing and vision difficulties to jaundice and an increased susceptibility to infection. Black women are twice as likely to have a preterm birth as white women, according to the CDC.
To identify pathogens that may contribute to preterm birth, Bravo studies microbes in both mothers and newborn premature babies, analyzing the data to find where microbes overlap between mother and baby.
“Our goal is to understand how oral microbes can manipulate the immune system to avoid maternal and fetal immune responses, because then health problems can take root before a baby is born,” Bravo said. “With this knowledge, we can uncover the mechanisms that contribute to adverse pregnancy outcomes that affect both mothers and infants, and create more babies with healthy foundations for healthier futures.”
A special advantage
There are more than 120 faculty, staff and students across all four UCSF schools working on microbiome research projects with the common goal of learning as much as possible about the human microbiome. Dental students like Bacino and Bravo appreciate how the interactions they have are advancing their oral microbiome research faster.
“Within the Lynch lab, we all share the commonality of studying microbes, but we work on different aspects,” Bacino said. “The lab is full of different perspectives that we bring to each other. We’re starting to see connections between different parts of the body, from head to toe, and that’s a great environment to study.”
Bravo said being a dental student working under the BCMM umbrella offers him useful opportunities for collaboration, mentoring and guidance. “I like working within different fields and approaches. I have a lot of flexibility in how I study and explore the oral microbiome.”
Lynch said the collaboration between clinicians and researchers in the Schools of Dentistry and Medicine gives UCSF a distinct advantage when it comes to oral microbiome discoveries.
“Collaboration is in our DNA at UCSF and is really what drives us. We collaborate across disciplines and focus on research that is tailored to specific issues that people face. It is the future of our rapid discovery and human research efforts. health,” he said. “The oral microbiome is relatively understudied and requires new tools to investigate it. We have developed these new tools, which allow us to examine the oral microbiome in unprecedented ways. These advantages are critical to the development of new therapies and disease prevention strategies.”
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