Despite decades of research, scientists still haven't worked out what causes many diseases: they include heart disease, Alzheimer's, type 2 diabetes and some cancers. Worldwide 70% of all deaths are attributed to these conditions: in the UK it is 90%.
These conditions usually start showing symptoms later in life, and more of us get them as we live longer. What they have in common is (A) inflammation, the method our immune system uses to kill invading cells and (B) they are not communicable to other people.
New evidence indicates that bacteria are covertly involved, invading organs, co-opting our own immune systems to boost their own survival and causing our illnesses. They tend to work very slowly, stay dormant for long periods or hide inside our cells. This makes them hard to grow in lab cultures. Now DNA sequencing has found bacteria in places they were not supposed to be, manipulating inflammation.
The worst culprits seem to be those that cause gum disease, which seem to play a role in a wide range of illnesses. Incidence of gum disease is: US 42% of those over 30 and 60% of those over 65, and in Germany 88% has been recorded. Many of the diseases of ageing - from rheumatoid arthritis to Parkinson's - are more likely, and more severe, in people with gum disease. There is evidence that treating treating gum disease goes with a lower incidence of heart attacks, diabetes, strokes and cancer.
Your mouth hosts more than 1,000 species of bacteria, in a stable community with the potentially bad ones kept in check by others. Elsewhere in the body, communities of bacteria live on a continuous sheet of cells, where the outermost layer is constantly shed, getting rid of invasive bacteria. But your teeth can't shed a layer like that, so bacteria live on a hard surface that actually pierces through the protective outer sheet of cells. The bacteria live in the plaque that builds up on your teeth. When plaque builds up enough to harden and spread under the gum, it triggers inflammation: immune cells flood in and destroy both microbes and our own infected cells. Untreated an oxygen poor pocket develops between gum and tooth. A few bacteria take advantage of this and multiply. In particular on of them, Porphyromonas gingivalis, disrupts the stable bacterial community and prolongs inflammation.
Most pathogens try to block or avoid inflammation, which normally kills them. But P. gingivalis perpetuates inflammation in a weakened form, which never quite destroys the bacteria but keeps trying - and killing your own cells in the process; the resulting debris is eaten by P. g, which unlike other bacteria feeds on protein. The process also liberates iron which the bacteria need, and which the body normally keeps locked up. The bacteria is able to escape into the bloodstream before the infected tooth falls out.
Once in the blood, the immune system makes antibodies, but these are more an indicator of its presence than protection, as P. g changes its surface proteins so it can hide in the white blood cells of the immune system. It also enters the cells lining arteries, but remains dormant; though it continues to activate or block different immune signals and may change a blood cell's gene expression to make it migrate to other sites of inflammation to feed on debris. The bacteria have been detected in inflamed tissue in the brain, aorta, heart, spleen, liver, kidneys, joints and pancreas in mice and, in many cases, in humans.
More than two thirds of all dementia is Alzheimer's, which is now the largest cause of death worldwide. A recent study found that gingipain, a protein digesting enzyme produced only by P.g, was found in 99% of brain samples from people who died with Alzheimer's, at levels corresponding with their condition. P.g was also found in the spinal fluid samples. Giving mice P.g caused symptoms of Alzheimer's, and blocking the gingipain reversed the damage. Half the samples from people who died without Alzheimer's also had gingipain but at lower levels. This was expected as damage can accumulate for 20 years before people show symptoms. Researchers in Sweden found that people with the highest genetic risk produce a specific form of an immune protein called ApoE that is destroyed in the disease, and that gingipains are better at destroying that ApoE than other forms.
Researchers have found P.g in the fatty deposits that line arterial walls and cause blood clots, causing heart attacks and strokes. P.g affects arteries much like high-fat diets and triggers atherosclerosis. Treating gum disease improves hardened arteries but doesn't reduce heart attacks or strokes because it doesn't get rid of the the P.g already in blood vessels.
There is also a link to type 2 diabetes, where sensitivity to insulin is lost. Diabetes worsens gum disease, but gum disease also worsens diabetes and treating it helps as much as adding a second drug to the treatment. Other evidence shows P.g acting directly in the liver and pancreas to cut insulin sensitivity.
People who drink more alcohol tend to have more P.g and are more susceptible to gum disease. Tobacco helps P.g to invade gum cells. Exercise, the only known way to lower your risk of Alzheimer's, improves gum disease by damping inflammation and ending P.g's feast of dead cells. One researcher believes that diet is also a factor; if our blood contains many dormant bacteria, they can be activated with free iron. A diet rich in red meat and sugar, or with too little fruit and vegetable, both increase the amount of free iron in the blood.
How can we stop P.g? It dodges our defences, hiding inside cells where antibodies can't reach it, and lying dormant making it invisible to antibiotics. Many of us already host P.g and routine gum abrasion, through eating and brushing your teeth, can release the microbes into your bloodstream, so spread it through your body. People with gum disease already make antibodies, but these seem to do little to stop it, so vaccines are unlikely to help. In studies on mice, it rapidly became resistant to antibiotics. Trying to block inflammation could leave us unprotected against other pathogens and conditions. It may be better to concentrate on blocking its ability to cause disease, perhaps by blocking gingipains. Pharmaceutical companies are working on drugs that block only specific inflammatory signals, but this is complex and will be a difficult challenge.
Source: The hidden cause of disease by Deborah MacKenzie in New Scientist, pp.42-46.
