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In the last few years a number of researchers have suggested that microbes may be triggering or somehow causing Alzheimer's disease. Various microbes have been suggested, and research is finding links with herpes viruses, fungi, other microbes, and gum disease (periodontal disease) microbes. Now another study proposes that the common bacteria Porphyromonas gingivalis - which causes chronic periodontal disease, is linked to the development of Alzheimer's disease.

Researchers have suggested that during an initial infection, the "infectious agent" (viruses, etc.) reaches the central nervous system and brain, then stays there in latent form (inactive) for years. And then when the immune system declines with age (which is a normal part of aging) - the microbes (virus, fungi, etc.) become reactivated and cause inflammation and the chain of events leading to Alzheimer's disease.

Note that in the recent study implicating P. gingivalis - the Cortexyme, Inc. company is doing the research and they, of course, are developing a product - so beware of bias. Also, the research done so far is in the earliest stages. But...it is exciting to see if further research (from them and from others) supports some sort of microbe, or several types of microbes, behind the development of Alzheimer's disease. Will we find that there is an "infectious cause" of Alzheimer's disease ("infection-induced neuroinflammation")? Because this means that there is a way to prevent or treat Alzheimer's disease - some sort of antimicrobial, antibiotic, antiviral, or antifungal. Stay tuned for further research.... From Medical Xpress:

Bacterial pathogen Porphyromonas gingivalis may contribute to Alzheimer's disease: Study

Cortexyme, Inc., a privately held, clinical-stage pharmaceutical company developing therapeutics to alter the course of Alzheimer's disease (AD) and other degenerative disorders, today announced publication of a foundational paper supporting its approach in Science Advances. In the paper, an international team of researchers led by Cortexyme co-founders Stephen Dominy, M.D. and Casey Lynch detail the role of a common bacterium, Porphyromonas gingivalis (Pg), in driving Alzheimer's disease pathology, and demonstrate the potential for small molecule inhibitors to block the pathogen.  ...continue reading "Periodontal Disease Link to Alzheimer’s Disease?"

A large study by researchers at the State University of NY, of 65,869 postmenopausal women found that those who have a history  of gum or periodontal disease also have an overall higher risk of cancer. The women with a history of periodontal disease also had an increased risk for several specific cancers: breast, esophageal, gallbladder, lung and melanoma cancers. This cancer and gum disease association occurred in both nonsmokers and smokers.

How is periodontal disease "promoting" cancer? How it occurs is still unclear, but one theory suggests the gum disease bacteria are in the saliva, which is swallowed, and so the bacteria get into the gut, esophagus, or lungs. Or bacteria from diseased gum tissues get into "systemic circulation" and so get to distant sites in the body.  One of the researchers pointed out that "Certain periodontal bacteria have been shown to promote inflammation even in tiny amounts, and these bacteria have been isolated from many organ systems and some cancers including esophageal cancers."

From Medscape: Gum Disease and Increased Link to Many Cancers

Brushing, flossing, and regular dental checkups appear to do much more than maintain a healthy smile. Now, a large prospective cohort study shows that postmenopausal women with a history of periodontal disease, including those who have never smoked, are at significantly increased overall risk for cancer as well as site-specific cancers, including lung, breast, esophageal, gallbladder, and melanoma skin cancers.

The study authors note that these results add to the growing body of evidence from smaller studies and studies in men that link periodontal disease to total cancer risk. The Centers for Disease Control and Prevention (CDC) estimate that 47% of adults 30 years of age and older in the United States have some form of periodontal disease, ranging from mild to severe. At age 65 years and older, however, 70% of adults have moderate to severe periodontal disease, according to the CDC.

The study involved almost 66,000 postmenopausal women in the United States, who were enrolled in the ongoing Women's Health Initiative Observational Study (WHI-OS). During a mean follow-up of 8.32 years, the team identified 7149 cancers and found that periodontal disease history was associated with a 14% increased total cancer risk. When analyses were limited to 34,097 never-smokers, there was also an increased risk for overall cancer.

An association between periodontal disease and site-specific cancers was observed in breast, lung, esophageal, gallbladder, and melanoma skin cancers. There was a borderline association with stomach cancer, the study authors report, and periodontal disease was not associated with cancers of the pancreas; liver; lower digestive tract organs; or lip, oral cavity, and pharynx combined. Similarly, there was no association with genitourinary and lymphoid and hematopoietic malignancies.

For the study, the investigators looked at periodontal disease information in 65,869 women aged 54 to 86 years at 40 US centers. Mean age was 68 years. Most women were non-Hispanic whites with some college education. All participants answered the question "Has a dentist or dental hygienist ever told you that you had periodontal or gum disease? (No/Yes)" between 1999 and 2003 on the annual Year-5 WHI-OS follow-up questionnaire. Cancer outcomes were documented through September 2013 with a maximum 15-year follow-up period.

 Women who reported a history of periodontal disease were also more likely to report a history of smoking, secondhand smoke exposure, alcohol use, hormone therapy (estrogen plus progestin), and a cancer diagnosis, the study authors report. At the same time, no significant differences were observed in body mass index, physical activity levels, or history of diabetes between women with periodontal disease and those without. [Original study.]

 Two articles about the link between Alzheimer's disease (AD) and microbes this past week: a study linking periodontal disease and Alzheimer's, and the other a journal editorial (written by an international team of 31 researchers) suggesting that we need to more closely look at the role of microbes in Alzheimer's disease, especially herpes virus, chlamydia and spirochaete bacteria.

This team is suggesting an "infectious cause" for Alzheimer's, an example being the reactivation of herpes simplex virus type 1 (HSV1) in the person. The researchers state that "regarding HSV1, about 100 publications by many groups indicate directly or indirectly that this virus is a major factor in the disease".  The team also mentions the possibility of fungi infection in some cases (see my November 6, 2015 post about a study finding fungal involvement). Both articles mention that treatment of the diseases with some form of antimicrobials or antivirals could possibly treat Alzheimer's disease, and that trails now need to be done.

From Science Daily: Link between gum disease and cognitive decline in Alzheimer’s

A new study has found a link between gum disease and greater rates of cognitive decline in people with early stages of Alzheimer's Disease. Periodontitis or gum disease is common in older people and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Higher levels of antibodies to periodontal bacteria are associated with an increase in levels of inflammatory molecules elsewhere in the body, which in turn has been linked to greater rates of cognitive decline in Alzheimer's disease in previous studies.

The presence of gum disease at baseline was associated with a six-fold increase in the rate of cognitive decline in participants over the six-month follow-up period of the study. Periodontitis at baseline was also associated with a relative increase in the pro-inflammatory state over the six-month follow-up period. The authors conclude that gum disease is associated with an increase in cognitive decline in Alzheimer's Disease, possibly via mechanisms linked to the body's inflammatory response.....However, growing evidence from a number of studies links the body's inflammatory response to increased rates of cognitive decline, suggesting that it would be worth exploring whether the treatment of gum disease might also benefit the treatment of dementia and Alzheimer's Disease.

From Journal of Alzheimer's Disease: Microbes and Alzheimer’s Disease

We are researchers and clinicians working on Alzheimer’s disease (AD) or related topics, and we write to express our concern that one particular aspect of the disease has been neglected, even though treatment based on it might slow or arrest AD progression. We refer to the many studies, mainly on humans, implicating specific microbes in the elderly brain, notably herpes simplex virus type 1 (HSV1), Chlamydia pneumoniae, and several types of spirochaete, in the etiology of AD [1–4]. Fungal infection of AD brain [5, 6] has also been described, as well as abnormal microbiota in AD patient blood [7]. The first observations of HSV1 in AD brain were reported almost three decades ago [8]. The ever-increasing number of these studies (now about 100 on HSV1 alone) warrants re-evaluation of the infection and AD concept.

AD is associated with neuronal loss and progressive synaptic dysfunction, accompanied by the deposition of amyloid-β (Aβ) peptide, a cleavage product of the amyloid-β protein precursor (AβPP), and abnormal forms of tau protein, markers that have been used as diagnostic criteria for the disease [9, 10]. These constitute the hallmarks of AD, but whether they are causes of AD or consequences is unknown. We suggest that these are indicators of an infectious etiology. In the case of AD, it is often not realized that microbes can cause chronic as well as acute diseases; that some microbes can remain latent in the body with the potential for reactivation, the effects of which might occur years after initial infection; and that people can be infected but not necessarily affected, such that ‘controls’, even if infected, are asymptomatic [2].

Regarding HSV1, about 100 publications by many groups indicate directly or indirectly that this virus is a major factor in the disease....The only opposing reports, two not detecting HSV1 DNA in elderly brains and another not finding an HSV1–APOE association, were published over a decade ago [76–78]. However, despite all the supportive evidence, the topic is often dismissed as ‘controversial’. One recalls the widespread opposition initially to data showing that viruses cause some types of cancer, and that a bacterium causes stomach ulcers.

In summary, we propose that infectious agents, including HSV1, Chlamydia pneumonia, and spirochetes, reach the CNS and remain there in latent form. These agents can undergo reactivation in the brain during aging, as the immune system declines, and during different types of stress (which similarly reactivate HSV1 in the periphery). The consequent neuronal damage— caused by direct viral action and by virus-induced inflammation— occurs recurrently, leading to (or acting as a cofactor for) progressive synaptic dysfunction, neuronal loss, and ultimately AD.

AD causes great emotional and physical harm to sufferers and their carers, as well as having enormously damaging economic consequences. Given the failure of the 413 trials of other types of therapy for AD carried out in the period 2002–2012 [79], antiviral/antimicrobial treatment of AD patients, notably those who are APOE ɛ 4 carriers, could rectify the ‘no drug works’ impasse. We propose that further research on the role of infectious agents in AD causation, including prospective trials of antimicrobial therapy, is now justified.

Image result for teeth, wikipedia Research found that postmenopausal women with periodontal disease (gum disease) were more likely to develop breast cancer than women who did not have the chronic inflammatory disease. And it's a bigger risk among those who currently smoke or quit smoking within the last 20 years. The interesting part is the fact that periodontal disease is a bacterial disease and that it results in inflammation. An earlier post discussed research that found that the human breast microbiome (microbial community) and specifically the bacteria, is different in healthy breasts (in the breast tissue) as compared to cancerous breasts. From Science Daily:

Periodontal disease associated with increased breast cancer risk in postmenopausal women

Postmenopausal women with periodontal disease were more likely to develop breast cancer than women who did not have the chronic inflammatory disease. A history of smoking significantly affected the women's risk, researchers report. Periodontal disease is a common condition that has been associated with heart disease, stroke, and diabetes. Previous research has found links between periodontal disease and oral, esophageal, head and neck, pancreatic, and lung cancers, so the researchers wanted to see if there was any relationship with breast cancer.

Jo L. Freudenheim, PhD, and colleagues monitored 73,737 postmenopausal women enrolled in the Women's Health Initiative Observational Study, none of whom had previous breast cancer. Periodontal disease was reported in 26.1 percent of the women. Because prior studies have shown that the effects of periodontal disease vary depending on whether a person smokes, researchers examined the associations stratified by smoking status.

After a mean follow-up time of 6.7 years, 2,124 women were diagnosed with breast cancer. The researchers found that among all women, the risk of breast cancer was 14 percent higher in women who had periodontal disease.

Among women who had quit smoking within the past 20 years, those with periodontal disease had a 36 percent higher risk of breast cancer. Women who were smoking at the time of this study had a 32 percent higher risk if they had periodontal disease, but the association was not statistically significant. Those who had never smoked and had quit more than 20 years ago had a 6 percent and 8 percent increased risk, respectively, if they had periodontal disease.

"We know that the bacteria in the mouths of current and former smokers who quit recently are different from those in the mouths of non-smokers," Freudenheim explained. One possible explanation for the link between periodontal disease and breast cancer is that those bacteria enter the body's circulation and ultimately affect breast tissue. However, further studies are needed to establish a causal link, Freudenheim said.

Interesting study that definitely needs follow-up to see if it also applies to women. Nice news for coffee drinkers - that coffee consumption may have protective effects against gum disease. From Medical Xpress:

Coffee drinkers—your gums may thank you

Coffee contains antioxidants. Antioxidants fight gum disease. Does coffee, then, help fight gum disease?  Lead author and 2014 DMD graduate Nathan Ng said, "We found that coffee consumption did not have an adverse effect on periodontal health, and, instead, may have protective effects against periodontal disease."

Coffee consumption was associated with a small but statistically significant reduction in number of teeth with periodontal bone loss. Researchers concluded that coffee consumption may be protective against periodontal bone loss in adult males—the group examined in the study.