The mouth provides a hospitable environment for many microorganisms. It is warm, nutrient-rich, continuously bathed with saliva, and has a pH of between 6.75 and 7.25. Hence the oral cavity is home to a rich microbiota, most of which are beneficial organisms and live in harmony with each other and the host.
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} #sub_M_L_P{ left:-130px; position: absolute; top: -30px; z-index: -6; } #sub_M_L{ width:334px; height:537px; background-image:url(‘userc/images/content_images/spt_apr/2014_08_22_12_20_37_67_2014_08_06_15_48_32_330_334_537_only-cells-cleaned.png’); } #sub_M_R_P { top: 600px; left: 560px; position: absolute; z-index: -4; } #sub_M_R{ width:334px; height:537px; background-image:url(‘userc/images/content_images/spt_apr/2014_08_22_12_20_37_67_2014_08_06_15_48_32_330_334_537_only-cells-cleaned.png’); } #sub_M_H_P{ left: -70px; margin-left: auto; margin-right: auto; position: absolute; /*top: -160px;*/ top: -247px; z-index: -30; } #sub_M_H{ width:439px; height:338px; background-image:url(‘userc/images/content_images/spt_apr/2014_08_22_12_20_04_721_2014_08_04_13_09_28_508_439_338_teeth_and_mouth.png’); background-repeat:no-repeat; } #sub_M_H_P_mini{ left: -70px; margin-left: auto; margin-right: auto; position: absolute; top: -178px; z-index: -31; } #sub_M_H_mini{ width:439px; height:338px; background-image:url(‘userc/images/content_images/spt_apr/2014_08_22_12_20_04_721_2014_08_04_13_09_28_508_439_338_teeth_and_mouth.png’); background-repeat:no-repeat; } #sub_M_C { background-color: #adccde; margin: 1.25em 0.625em; position: relative; } #sptLogoDiv{ margin-left: auto; margin-right: auto; /*max-width: 58em;*/ max-width: 35em; } /* overwrite of master styles END */ The pros and cons of oral bacteria By Rosemary Frei, MSc, HuangshanDental.com contributing writer The mouth provides a hospitable environment for many microorganisms. It is warm, nutrient-rich, continuously bathed with saliva, and has a pH of between 6.75 and 7.25. Hence the oral cavity is home to a rich microbiota, most of which are beneficial organisms and live in harmony with each other and the host.
The presence of microbes is in fact essential for maintaining the normal physiology of the oral cavity. While this symbiosis is usually stable and mutually beneficial, if some external force changes the balance, the result can be gingivitis, dental caries, or periodontal disease.
A significant body of knowledge is now available on how to maintain a healthy ecology of microbiota and keep diseases at bay. There is also a growing number of oral health products, from lozenges to mouthwashes, designed to optimize the balance of bacteria in the mouth, retain their beneficial characteristics, and suppress their potentially harmful impact.
“It’s actually too much plaque and plaque in the wrong places that are bad for us.” – Philip D. Marsh, PhD, Leeds Dental Institute
Denizens of the oral cavity
Philip D. Marsh, PhD, is one of the leaders in this area and has been publishing papers on oral microbes for more than 35 years. He advises caution when seeking to interfere with the microbiological balance in the mouth in a bid to stem oral diseases.
“What we’ve been brought up with is ‘Plaque is bad — get rid of it.’ But it’s actually too much plaque and plaque in the wrong places that are bad for us. We want to prevent the buildup of levels of organisms, particularly in hard-to-reach places of the mouth, that could lead to disease,” said Marsh, a professor of oral microbiology at Leeds Dental Institute. “Pushing to have an ultraclean mouth isn’t beneficial to us; we should be trying to maintain our natural microbiota at levels compatible with oral health in order to preserve their beneficial activities.”
“To eliminate all the bacteria is impractical.” – Yiping Weng Han, PhD, Case Western University
Aaron Weinberg, DMD, PhD, agrees that trying to sterilize the mouth may lead the way for exogenous, deleterious organisms to colonize it instead.
“You don’t want a sterile mouth; you want a mouth that has primarily good bacteria in it, in order to keep exogenous microorganisms out and prevent them from colonizing the mouth,” said Dr. Weinberg, the associate dean for research at the Case Western Reserve University School of Dental Medicine.
Another faculty member at the Case Western Reserve University dental school who specializes in oral bacteria has a similar view. Yiping Weng Han, PhD, a professor of periodontics, pathology, and reproductive biology, focuses on Fusobacterium nucleatum, as does Dr. Weinberg.
According to Dr. Han, the ultimate research goal is not to “search out and destroy” all cells of F. nucleatum, although the microbe is associated with serious diseases in the oral cavity and throughout the body.
“First of all, to eliminate all the bacteria is impractical, and it’s also not ideal because then you have a surface that exogenous bacteria can colonize,” she said. “Also, if we eliminate one species, we don’t yet know the effects because there is a lot of interdependence among different species.”
The importance of homeostasis
Biofilms form in a rapid sequence of events and mature into a complex, interacting community of microorganisms that have different properties than when they are present in isolation. The resulting community is more resistant to antimicrobial agents, stress, and host defenses, for example. Biofilms act as a barrier to organisms in the air, water, and food with which people constantly come into contact.
Among the main bacteria residing in the mouth — including in biofilms — in both health and disease are species that have traditionally been considered to be “bad,” such as Streptococcus mutans, Tannerella forsythia, Porphyromonas gingivalis, and F. nucleatum. The bacteria that have been picked for the “good” team include S. sanguinis, S. oralis, Actinomyces naeslundii, Neisseria subflava, and Veillonella dispar.
However, it is now acknowledged that this is an artificial distinction. For example, F. nucleatum has been shown by the teams led by Drs. Weinberg and Han to have properties that can be exploited to benefit human health. But F. nucleatum is also associated with gingivitis and a raft of serious diseases elsewhere in the body.
“While it is debatable whether F. nucleatum is a ‘good’ or ‘bad’ bug in the oral cavity, as soon as this fastidious anaerobe leaves its natural habitat — that is, the mouth — it becomes a bona fide ‘bad’ bug,” Dr. Han noted.
Several decades ago, researchers likened the interactions in the mouth to ecological systems in nature. Breakdowns in the normal balance between species on the planet can result from a number of causes and hence do not have one exclusive etiology. Similarly, Dr. Marsh believes, in the mouth, the key steps in the descent into disease relate to particular shifts in environmental circumstances rather than the actions of specific sets of microorganisms.
“If you take 100 examples of an organism that is implicated in dental caries — S. mutans, for example — you can find some that are very good at making acid and some that are not quite as good,” Dr. Marsh explained. “We’re not dealing with bacteria that produce toxins. We’re dealing with bacteria whose metabolic end products can be deleterious and which grow best in the presence of those end products.”
“If we could use the peptides as an adjunct to conventional antibiotics, we may be able to reduce the antibiotic resistance that is prevalent in a number of bacteria.” – Aaron Weinberg, DMD, PhD, Case Western University
Dr. Weinberg has a similar view.
“This concept of ‘pathogenic organisms’ is really overutilized,” he said. “Because when you say ‘pathogenic organism,’ you’re equating it to something that shouldn’t be in the body. But in oral disease, these are organisms that have evolved over the millennia to grow and coexist with the host, albeit in low numbers.”
Dr. Weinberg’s own research with F. nucleatum indicates that when the bacterium comes into contact with oral epithelial cells, the cells produce small proteins, which he has dubbed human beta-defensins. These are a group of antimicrobial peptides that kill bacteria, fungi, and encapsulated viruses, and represent the first line of defense for the mouth’s lining. Dr. Weinberg’s team has also isolated and characterized, from the outer membrane of F. nucleatum, the F. nucleatum-associated defensin inducer (FAD-I), which promotes the expression of human beta-defensins (Journal of Biological Chemistry, November 19, 2010, Vol. 285:47, pp. 36523-36531).
The team now is working to identify the “hot spots” of FAD-I that are directly responsible for this activity. The goal is eventually to be able to control and direct the production of endogenous antimicrobial peptides in the oral mucosa and other vulnerable mucosal sites of the body.
“The idea is to use FAD-I in certain situations in the oral cavity where you want a particular site to be more sterile than others,” Dr. Weinberg explained. “If you can induce the production of these peptides — which are nature’s own antibiotics — we could possibly change the microflora of that particular site. And if we could use the peptides as an adjunct to conventional antibiotics, we may be able to reduce the antibiotic resistance that is prevalent in a number of bacteria.”
For their part, Dr. Han and her co-investigators have begun identifying the mechanisms that allow F. nucleatum to move from the mouth into the bloodstream and thence throughout the body — taking other bacteria with it and leaving destruction in their path (Molecular Microbiology, December 2011, Vol. 82:6, pp. 1468-1480). Her team has shown that F. nucleatum can induce preterm birth and stillbirth in animals and humans (see, for example, Obstetrics & Gynecology, February 2010, Vol. 115:suppl 2, part 2, pp. 442-445). Other researchers have linked it to colorectal cancer (Genome Research, October 18, 2011) and infections and abscesses in all the internal organs, including the brain and lungs.
A fine balance — that can be destroyed
In a healthy mouth, biofilms perform many positive functions. As just one example, 25% of nitrates from vegetables re-emerge in the saliva. In the mouth, the nitrates are converted to nitrites, which in turn are converted to nitric oxide in the stomach (Free Radical Biology & Medicine, April 2009, Vol. 46:8, pp. 1068-1075). Nitric oxide has many important functions in maintaining good health, including helping control blood pressure.
In addition, some beneficial bacteria are now recognized as being capable of signaling to their hosts — us — that they are not harmful.
“It has been shown — first in the gut and now there are a couple of papers in dental journals on this relating to oral bacteria — that the bacteria ‘talk’ to the host to indicate they are beneficial: ‘Don’t overreact to us, because we’re doing you good.’ That allows the host to focus, instead, on searching for microorganisms that are actually potential threats,” said Dr. Marsh, citing one of several papers on the topic (Infection and Immunity, September 2008, Vol. 76:9, pp. 4163-4175).
When the natural balance in the mouth shifts significantly, bacteria with harmful effects can begin to dominate. pH and nutrient status are believed to be two of the main drivers of the descent into disease. For example, in people who have a diet high in simple carbohydrates or sugars, the pH of the mouth will drop more frequently and to lower levels than in people with a more healthful diet. This in turn leads to a significant increase in acid-tolerating bacteria such as S. mutans and the displacement of oral-health-associated, neutral-pH-loving bacteria.
Another example is the increase in gram-negative proteolytic bacteria in the presence of the inflammatory response that accompanies perio
