Microbes in normally sterile body sites
One of the more remarkable developments in recent years in the field of health and aging is the recognition that bacteria and other microbes such as fungi can be found in many body sites that were formerly considered to be sterile — the blood stream for instance, or the brain. In this article, I’ll discuss how iron and bacteria combine to promote aging and disease.
I covered this idea in a book review on how bacteria may be largely responsible for many of the ills of aging.
Many body sites are normally covered or filled with bacteria: the gut, the skin, the mouth and throat, for example. But these sites can all be considered to be outside the body. The gut and skin barriers and mucus membranes function to keep bacteria where they belong and to prevent bacterial and fungal illness.
When microbes penetrate to normally sterile body sites, such as the bloodstream, they can cause illness, a fact which has been known at least since the time of Louis Pasteur and Robert Koch.
What current research is uncovering is that apparently healthy people often — maybe always — carry bacteria in normally sterile sites, and that they may be the cause of diseases previously thought non-infectious — heart disease and Alzheimer’s disease, to name two.
Bacteria and other microbes can be placed into one of three categories with regard to their infectiousness: pathogens, opportunistic pathogens, and non-pathogens.
- Pathogens: The pathogens are well-known, for example Yersinia pestis, which causes the plague, or Francisella tularenis, which causes tularemia. Both of these can cause fatal disease in an otherwise healthy human, and generally you don’t want to be anywhere near them.
- Opportunistic pathogens are organisms like E. coli or Staphylococcus aureus, which live in and around healthy people and normally cause no problems. But if they get into body sites where they don’t belong, such as beneath the skin, in the bloodstream, or in the urinary tract, or in people who have compromised immune systems, they can cause disease.
- Non-pathogens live on humans, or in soil and water, and do not cause disease.
The story of microbes in normally sterile sites as the cause of aging and disease is largely the story of non-pathogens and/or normally sterile sites like the bloodstream. We already knew about the disease-causing effects of other bacteria, and we knew that blood is not supposed to have microbes in it.
Microbes as the cause of chronic disease
How do we know that bacteria and other microbes cause chronic disease? Are they just bystanders or actual perpetrators?
Take the case of Alzheimer’s disease. Bacteria and fungi have been found in the brains of Alzheimer’s patients, but not in those of controls.
This begins to satisfy the first of Koch’s postulates: the organism must be present in all cases of the disease. Until recently, culturing the microbes, the second of Koch’s postulates, has been difficult, but scientists are working on that.
Culturing the microbes may be difficult. It’s estimated that less than 1% of bacteria can be cultured, which has become known as “the great plate count anomaly”. What this means is that most of the bacteria seen under a microscope cannot be grown in a laboratory, whether because they are dead, non-viable, dormant, or just don’t thrive in laboratory culture media and conditions.1
So, only until the advent of DNA probes has it been discovered that many body sites formerly considered sterile are in fact loaded with microbes.
One of the key factors in Alzheimer’s and other diseases of aging, and of aging itself, is inflammation — an activation of the immune system.
Bacteria and other microbes activate the immune system — that’s what the immune system does, it activates to protect the body from invaders.
Other lines of evidence of a microbial cause of Alzheimer’s include:
- the fact that it only strikes old people, and they have weakened immune systems
- periodontal disease, in which bacteria infect the gums, is associated with Alzheimer’s 2 Antibodies to periodontal pathogens are a risk factor for Alzheimer’s.3
Iron and microbes
Virtually all living things require iron to grow, metabolize, and reproduce, and bacteria are no exception.
A key factor in the successful bacterial invasion, colonization, and/or infection of an organism is its ability to get enough iron. If it can’t do so, then it may remain dormant and unsuccessful, as it’s unable to commandeer enough iron to grow.
Because bacteria and other invading microbes require iron, organisms including humans have evolved a number of means of withholding iron from invading microbes. Perhaps the most important is the protein molecule ferritin, which encloses and holds iron atoms tightly in its core and makes it unavailable to microbes that need it.
In turn, microbes have evolved ways to get that iron, and these ways are often very important to a microbe’s pathogenicity — its ability to invade an organism and cause disease.
It’s an evolutionary arms race between host and microbe.
Microbes have developed methods of destroying iron-containing molecules and grabbing the iron within, or have developed their own molecules with a high affinity for iron, and these latch on to any free iron within the organism.
Free iron is the key factor, the bottleneck, that microbes need.
It’s well established that iron supplementation causes infections. In recent years, the seeding of iron in the oceans has been proposed as a method of fighting global warming. In essence, dumping free iron in the form of iron powder eliminates the iron bottleneck for microbial growth, and algae and plankton grow abundantly. This is a good analogy for what happens in the human body when too much iron is available.
Physiological insults can also increase the amount of free iron inside the body and set the stage for microbial infection. Oxidative stress, which increases in aging, causes the release of free iron from ferritin. Solar radiation causes release of free iron in the skin, and this is critical to the mechanism of sun-caused skin damage.4
Limiting the amount of free iron is crucial in thwarting infections.
If Alzheimer’s and other chronic diseases are caused by infections, then controlling iron could stop them. Indeed, decreasing the amount of iron in the body either through phlebotomy (bloodletting) or iron chelators has been proposed as a method to treat Alzheimer’s.5
Douglas Kell and colleagues, who have done important work in this area, have recently proposed that iron activates dormant bacteria in the brain to cause Alzheimer’s.6 They write:
The progression of Alzheimer’s disease (AD) is accompanied by a great many observable changes, both molecular and physiological. These include oxidative stress, neuroinflammation, and (more proximal to cognitive decline) the death of neuronal and other cells. … We review the evidence that iron dysregulation is one of the central causative pathway elements here, as this can cause each of the above effects. In addition, we review the evidence that dormant, non-growing bacteria are a crucial feature of AD, that their growth in vivo is normally limited by a lack of free iron, and that it is this iron dysregulation that is an important factor in their resuscitation. Indeed, bacterial cells can be observed by ultrastructural microscopy in the blood of AD patients. A consequence of this is that the growing cells can shed highly inflammatory components such as lipopolysaccharides (LPS). These too are known to be able to induce (apoptotic and pyroptotic) neuronal cell death… This integrative systems approach has strong predictive power, indicating (as has indeed been shown) that both natural and pharmaceutical iron chelators might have useful protective roles in arresting cognitive decline, and that a further assessment of the role of microbes in AD development is more than highly warranted.
Alzheimer’s disease is a signature malady of aging, and if iron is implicated in it, then we may justifiably speculate that iron is involved in other diseases of aging, and in aging itself.
Indeed, iron has been implicated in heart disease, cancer, and diabetes, to name but a few diseases.
While free iron catalyzes harmful chemical reactions that damage cellular components and proteins, its role as a catalyst for bacterial growth, which then causes the diseases of aging, lends a new perspective on how iron causes aging.
Kell et al. also argue that many other chronic, inflammatory diseases are caused by infectious microbes, and that iron may be involved in their successful invasions of human tissue.7
Where do these microbes originate? Humans have protective barrier functions designed to keep microbes where they belong; as noted, the skin, the gut barrier, and mucus membranes do this.
But these barriers are not perfect, and microbes can slip through them on occasion, or in certain pathological states.
In most cases, DNA sequencing has found that most of these disease-causing microbes that are present in normally sterile sites originate in the gut, and secondarily from the oral cavity.
Leaky gut is the condition in which gut microbes, or their constituent parts such as lipopolysaccharides (LPS), slip past the gut barrier and into the body, there to cause damage or infection. In periodontitis, bacteria from infected gums and bone sheds into the bloodstream.
Kell and colleagues note that tiny amounts of LPS interact with fibrinogen, a blood-clotting protein, and cause hypercoagulability, the tendency of blood to clot faster than normal. This in turn increases the risk of blood clots in veins and arteries, as well as stroke and heart attack.
Hypercoagulability is characteristic of aging. If iron revive dormant bacteria, which then produces LPS and activates the coagulation system, then here’s another way that iron and bacteria synergize to cause disease.
The study of bacteria and other microbes in sites that were formerly thought sterile is, if not in its infancy, relatively new. Much more remains to be learned about their disease-causing effects, how they got there, what types of microbes they are, and how to prevent their occurrence.
It is well-known, however, that bacteria need iron to thrive, and without it they wither away, become dormant, or die.
Therefore, as documented in my book Dumping Iron, keeping iron levels low and well-controlled can stave off the ravages and illnesses of aging. In my view, iron is a critical factor in aging that so many scientists are overlooking. Whether it is so by virtue of its high reactivity with biological structures, by its role in feeding microbes, or both, remains to be seen.
(NB: As this is a huge topic, not all possible references have been included, but many of them are found in my other articles which are linked above.)
PS: For much more on the role of iron in aging and disease, see my book, Dumping Iron: How to Ditch This Secret Killer and Reclaim Your Health.
PPS: Check out my Supplements Buying Guide for Men. Includes iron chelators!
- Grice, Elizabeth A., et al. “A diversity profile of the human skin microbiota.”Genome Research 18.7 (2008): 1043. ↩
- Watts, Amber, Eileen M. Crimmins, and Margaret Gatz. “Inflammation as a potential mediator for the association between periodontal disease and Alzheimer’s disease.” (2008). ↩
- Stein, Pamela Sparks, et al. “Serum antibodies to periodontal pathogens are a risk factor for Alzheimer’s disease.” Alzheimer’s & Dementia 8.3 (2012): 196-203. ↩
- Bissett, Donald L., Ranjit Chatterjee, and Daniel P. Hannon. “CHRONIC ULTRAVIOLET RADIATION‐INDUCED INCREASE IN SKIN IRON and THE PHOTOPROTECTIVE EFFECT OF TOPICALLY APPLIED IRON CHELATORS 1.” Photochemistry and photobiology 54.2 (1991): 215-223. ↩
- Dwyer, Barney E., et al. “Getting the iron out: Phlebotomy for Alzheimer’s disease?.” Medical hypotheses 72.5 (2009): 504-509. ↩
- Pretorius, Etheresia, Janette Bester, and Douglas B. Kell. “A Bacterial Component to Alzheimer’s-Type Dementia Seen via a Systems Biology Approach that Links Iron Dysregulation and Inflammagen Shedding to Disease.” Journal of Alzheimer’s Disease Preprint (2016): 1-20. ↩
- Potgieter, Marnie, et al. “The dormant blood microbiome in chronic, inflammatory diseases.” FEMS microbiology reviews (2015): fuv013. ↩
I’ve been all but convinced of germ-theory of CHD for a few years.
First, there’s the anti-microbial properties of vit K2 that I’ve commented about before.
Another one I’ve seen, but don’t think I’ve shared here, is that statins were originally created by Japanese researchers looking for a new class of antibiotic. IIRC, statins proved to be so-so as antibiotics. But, if you assume that their efficacy is anti-microbial related instead of cholesterol-lowering, it would explain why the only population to which there is statistically significant efficacy is men with a history of myocardial infraction. Those are the ones necessarily positive for CHD infection. The MI event is the “clinical test.” Statins attack the infection, and probably help to break-up, or at least arrest, plaque formation as a pleasant two-fer.
And now, of course, iron fits beautifully with the germ-theory as well. BTW, what’s the first thing men are told to do when they are high-risk for heart-attack: cut-out red meat! Once again, they have the why backwards. I’d wager it’s not the saturated fat in red-meat that’s killing those men, it’s the iron.
About the only thing I’ve come across that doesn’t fit beautifully with the germ-theory is Ivor Cummin’s connecting dots between CHD and insulin; which, there may be a connection there, and I’ve just missed it. I seem to recall there being an immune-system and cancer relationship, and I know there is an insulin and cancer relationship, so, all the same, I don’t think one can say germ-theory and insulin-theory contradict each other.
Hi Allan, great comment. The only thing I can add is that insulin resistance and diabetes are connected to iron dysregulation – more free, unbound iron – though whether as cause or effect remains to be seen. However, phlebotomy improves insulin resistance. It also improves gout – is there an infectious cause there?
I don’t know, seems a little too tidy. I will of course, defer to your extensive experience in research, but I would caution against fitting any conclusions to accommodate hypotheses…I know that is not something that you would necessarily overlook. Most of this seems to “fit” but alas, some of it doesn’t so that naturally changes the dynamics of it some..
Perhaps I just don’t understand enough about K2 but the idea that it is antimicrobial just doesn’t sit well with me. Firstly, it is quite prevalent in foods that are also teeming with microbes; natto, cheese, yogurt, etc. Secondly, studies have shown that the introduction of antimicrobial agents into a physiology is correlated with a dearth of K2. So, if anything, K2 appears to be pro-microbial in light of the last two considerations.
I might be missing something, but perhaps not all things human wellness need to be so intricate. I believe that the notion of K2 as an “usher” for calcium and other minerals is intricate enough, as evidenced by the general public’s total lack of awareness of this vital nutrient. As far as I can see, just about every malady with which K2 and it’s deficiencies are implicated, there seems to be a mechanical relationship and this alone could be the complete story….or it might not.
But it makes perfect sense, to name but one such malady, that calcified plaque, which contributes to atherosclerosis, can be avoided if the proper amount of circulating K2 were in effect.
Outside of K2, another example of over -speculation would be in the case of the advice to a cardiac patient to cut out the red meat for a while. Sure, it sounds like solid advice as if there anything that is high in iron, it would be red meat but I don’t believe that is why those type patients originally got that advice as I would bet it was more about the significant source of saturated fat that red meat is also known for as it relates to the still pervasive paradigms of conventional medicine….
I just wonder how we “put the pieces together” at times.