We have been building towards this moment in medicine for 30 years. Thirty years in the genomic age is not a long time. In medicine, crystalline moments can accrue over a millennium, until a principle is recognized.  Such patiently acquired knowledge is not easily sacrificed. Doctors expect that half of what they learned in medical school will be replaced before they retire – they just don’t know which half.

An example of this from 1982: Warren and Marshall posited that bacteria could live in stomach acid and cause ulcers. The received medical wisdom of the time was that nothing could live in hydrochloric acid. For their trouble, they were almost drummed out of the Australian medical community. However, in 2005 they were awarded the Nobel Prize for medicine. Their discovery was actually part of re-imagining microbiology.  Legionnaire’s bacteria were found in hot water ventilation systems in 1978; sulfur-metabolizing bacteria were found in deep-sea thermal vents in 1979.

DNA technology now allows us to find the footprints of bacteria in places where finding live bacteria would be impossible. One proposed mechanism is that the bacteria were present, exhausted the nutrients, died, but left their DNA trace. We now recognize that each of us has a symbiotic relationship with 4-5 pounds of bacteria, fungi, and viruses that live both in and on us called the microbiome. DNA technology has revealed some traces of microbiome DNA among our genes, which is quantum leap in the definition of intimate relations. The components of this microbiome can change quickly, and may have had more to do with human adaptation than DNA, where evolution takes generations to affect more permanent adjustment. Our genome is 22,000 genes, a garden tomato has about 60,000 genes, and the microbiome has about 400 million genes.

The American Heart Association published a review of 537 publications (meta-analysis) which they claimed illustrated that dental bacteria did not show a “cause-and-effect” relationship with heart disease. As Shiller said, “against ignorance even the Gods themselves struggle in vain.” Bacteriologic relationships are exploding everywhere, but the AHA cannot sacrifice the old lessons for the new.

The AHA article (Circulation. published online April 18, 2013) engages in willful ignorance typical of large reviews  (good studies are discarded because they were small, primarily observational, with which the author disagrees.) The bottom line was that better oral care was not as effective as cholesterol control to prevent atherosclerosis, statin drugs above all. The press had a field day “Gum Disease Doesn’t Cause Heart Disease After All” (Time Magazine). The day after publication, I could not find one note of caution among the first 100 Google entries. (See note on “crowding out” at the end of the essay.)

However, this time even a behemoth like the American Heart Association could not silence debate.  Retraction Watch, a monitoring website, highlighted articles left out of the AHA review. Many physicians rejected the standard of “cause-and-effect” proposed in the AHA review. Cause-and-effect will never explain multi-factorial illnesses. Even Dr. Koch, the 19th century German researcher who coined the cause-and-effect postulates that bear his name, discarded his own work as he concluded biology was more shades of grey.

The AHA article in Circulation basically recommended sticking with statin drugs as the proven preventative, and belittled periodontal care as lacking direct evidence. A month later, the authors issued a clarification that periodontal care should be considered part of heart disease prevention because it reduces vascular inflammation. A month later, the American Dental Association published its disagreement:

Periodontitis is associated with increased risk of developing atherosclerosis; this association is independent and cannot be attributed to shared risk factors….The risks associated with the treatment of periodontitis are low and are outweighed by therapy-mediated benefits; treatment typically does not include systemic adjunctive pharmacotherapies that may result in adverse side effects. Periodontal care is much lower risk than the statin drugs and appears to lower risks by a different mechanism.

Control of oral bacteria can improve cardiac outcomes by unique mechanisms. And here is where the new evidence gets really interesting, because oral bacteria are popping up all over the body. A recent study by the University of Central Lancashire in England, published in the Journal of Alzheimer’s Disease, shows that bacteria components typically associated with gum disease (gingivitis) have been found in the brains of those who suffer from Alzheimer’s disease. The bacteria were not there to be cultured, but evidence of their presence was indisputable.

Recent studies on antibiotics in back pain were better; real bacteria were cultured and some people experienced relief from back pain with treatment.  The Spine Centre of Southern Denmark hypothesized that a certain x-ray change that frequently accompanied back pain (Modic I change) might represent inflammation from a bacterial infection. An experiment was done where they cultured disc material from surgeries on patients with no recent antibiotic usage.

Roughly half of what should have been sterile discs were positive for cultures of Propionibacterium acnes, bacteria primarily found in the mouth. The same researcher, Hanne B. Albert, in the The European Spine Journal reported on a group of 162 patients with no history of surgery or antibiotic usage and at least 6 months of back pain and Modic I changes on xray. Half were treated with Amoxicillin/Clavulanate (Augmentin) for 100 days. The treated group improved markedly over the control group. More important, the improvement persisted for an additional six months after treatment.

So while DNA technology is opening windows on these relationships, the real wizard is our imaginations. Danish researchers went from dental bacteria to bone inflammation to spinal discs. A British group went from noting Alzheimer’s patients having gum disease to dental bacteria traces in the brains of Alzheimer’s patients. This is medical research at warp speed.

It is thirty years later; the cast of characters is different, but the moment is similar. The American Heart Association, playing the role of the Australian Medical Society, has staked out the indefensible territory of the past. The tide of science shows that bacteria and humans have complex relationships, including such heretofore inviolate places as intervertebral discs. While the AHA is waiting for “cause-and-effect” proof, more subtle relationships of bacteria triggering inflammation in new ways will be characterized. In the meanwhile, getting your teeth cleaned and scaled, and using a dental irrigator (Waterpik) with dilute hydrogen peroxide would be a good start.

 

 

One note on “crowding out” – it is frequently permanent. The Women’s Health Iniative declared that hormone therapy increased heart disease and breast cancer in women when published in 2002 has been cited by 6,000 other publications since. When the Yale School of Medicine analyzed the WHI data ten years later, it demonstrated that hormones decreased cardiac events in women age 50-59 by 25%. The findings were endorsed by Jo Ann Manson, MD, the director of the WHI. The 25% decline in cardiac events is the largest improvement in cardiac prevention in medical history, but the Yale article has exactly 4 citations since publication in 2011. Bad studies can crowd out good ones, and the public is the loser.

 

References

 

Periodontal Disease and Atherosclerotic Vascular Disease: Does the Evidence Support an Independent Association?: A Scientific Statement From the American Heart Association Peter B. Lockhart, Ann F. Bolger, Panos N. Papapanou, Olusegun Osinbowale, Maurizio

Trevisan, Matthew E. Levison, Kathryn A. Taubert, Jane W. Newburger, Heather L. Gornik, Michael H. Gewitz, Walter R. Wilson, Sidney C. Smith, Jr and Larry M. Baddour

Circulation. published online April 18, 2012

Yale J Biol Med. 2011 March; 84(1): 39–42. Shook, Lydia

The Journal of the American Dental Association (August 1, 2012) 143, 826-828 © August 1, 2012 American Dental Association

Periodontitis and atherosclerotic vascular disease: What we know and why it is important. Panos N. Papapanou, DDS, PhD

Poole S, Singhrao S, Kesavalu L. Determining the Presence of Periodontopathic Virulence Factors in Short-Term Postmortem Alzheimer’s Disease Brain Tissue. Journal of Alzheimer’s Disease. 2013.

 

James Katz MD

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