6 replies to this topic

[Kalliste]

This is an interesting topic that I think about sometimes. It gets a lot of coverage on some more conspiracy-sided websites because it gives some credence to their pet-theory that all cancers are really fungi or something. That seems like nonsense to me. But this is an interesting subject anyway, one that might influence what supplements we take and so on.

In general, I'm always interested in those things we don't know, looking back at health 25 years from now will be interesting as more and more is uncovered (nanobacteria etc).

 

Abstract

Blood in healthy organisms is seen as a ‘sterile’ environment: it lacks proliferating microbes. Dormant or not-immediately-culturable forms are not absent, however, as intracellular dormancy is well established. We highlight here that a great many pathogens can survive in blood and inside erythrocytes. ‘Non-culturability’, reflected by discrepancies between plate counts and total counts, is commonplace in environmental microbiology. It is overcome by improved culturing methods, and we asked how common this would be in blood. A number of recent, sequence-based and ultramicroscopic studies have uncovered an authentic blood microbiome in a number of non-communicable diseases. The chief origin of these microbes is the gut microbiome (especially when it shifts composition to a pathogenic state, known as ‘dysbiosis’). Another source is microbes translocated from the oral cavity. ‘Dysbiosis’ is also used to describe translocation of cells into blood or other tissues. To avoid ambiguity, we here use the term ‘atopobiosis’ for microbes that appear in places other than their normal location. Atopobiosis may contribute to the dynamics of a variety of inflammatory diseases. Overall, it seems that many more chronic, non-communicable, inflammatory diseases may have a microbial component than are presently considered, and may be treatable using bactericidal antibiotics or vaccines.

 

CONCLUDING REMARKS AND PROSPECTIVE EXPERIMENTS

‘Non-culturable’ (which should be called ‘not-easily-culturable’ or ‘not-yet-cultured’) microbes are commonplace in the ‘environmental microbiology’ of soil and water, and the blood certainly represents an ‘environment’. As we show here, there is a large and scattered literature, increasing in size, to the effect that there might be a (mainly dormant) microbial component in a variety of chronic diseases that are normally considered to be non-microbial or non-communicable in nature, even when microbes appear absent by culturability criteria. Our previous work (e.g. Bester et al. 2013; Pretorius et al. 2013, 2014a; Kell and Pretorius 2014, 2015; Pretorius and Kell 2014) has implied iron dysregulation as a regular accompaniment to, and probable contributory factor for, a variety of similar diseases, all of which have an inflammatory component. We argue here that there is also a microbial contribution to this in the blood, and it is not unreasonable that the microbial requirement for iron means that, despite the oxidative stress it can entail (Touati 2000; Kell 2009, 2010), microbes may be anticipated to increase in prevalence when iron is free (e.g. Ratledge 2007; Clifton, Corrent and Strong 2009; Sia, Allred and Raymond 2013; Chu et al. 2014) and available (D'Onofrio et al. 2010), probably behaving in a social manner (Kell, Kaprelyants and Grafen 1995; West and Buckling 2003; Diggle et al. 2007; Harrison and Buckling 2009).

We have here pointed up the likelihood of a steady crop of effectively dormant microbes being a feature of blood biology in chronically diseased humans, including those with non-communicable diseases. As with any complex system, the magnitude of any component is affected by the kinetics of every relevant step; while the precise nature of all the interactions is uncertain, Fig. 8 describes the general network—the first step in any systems analysis (Kell 2006; Kell and Knowles 2006).

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Figure 8.

Relationships between a dormant blood microbiome and chronic disease dyamics.

 

Consequently, we recognize that the analysis above has largely been qualitative (the ‘presence’ of a microbial component in a specific disease is a qualitative statement). However, chronic, non-communicable diseases are very far from being static (and thousands of human genes change their expression at least 2-fold even on a diurnal basis; Zhang et al. 2014b). Thus, a clear further issue is to seek to understand how the blood microbiome may co-vary with the day-to-day dynamics of chronic diseases. For example, rheumatoid arthritis has circadian rhythms (Straub and Cutolo 2007) and is well known to provide significant variations (‘flares’; Flurey et al. 2014) in severity at different times. A reasonable strategy is thus to look for changes in a detectable blood microbiome in this and other diseases that show such flares. As with H. pylori and stomach ulcers (and cancer), the simple prediction is that bactericidal antibiotics should be of value in the treatment of such supposedly non-communicable diseases. Indeed, this prediction is borne out for diseases such as rheumatoid arthritis (Ogrendik 2009a, 2013a; Kwiatkowska and Maślińska 2012) and multiple sclerosis (Ochoa-Repáraz et al. 2009; 2011), while antipneumococcal vaccination has shown efficacy in preventing stroke (Vila-Corcoles et al. 2014). Of course, events such as heart attacks and strokes (and see Table 4) may also be seen as sudden increases in severity of an underlying condition, and in some cases (such as the much increased likelihood of strokes after subarachnoid haemorrhages; McMahon et al. 2013), analysis of changes in the blood microbiome might prove predictive.

The obvious next tasks are thus to relate the number and nature of blood microbes observed in cases such as the above to microbial sequences and antigens that can be detected in aliquots of the same samples (e.g. Salipante et al. 2013, 2015), to determine the physiological state of the various microbes (including e.g. whether they are L-forms), and to establish methods to bring them (back) into culture. Since microbes, inflammation and various syndromes are such common co-occurrences (as are coagulopathies; Kell and Pretorius 2015), longitudinal studies will have a specially important role, as they will both show the dynamics and be able to help discriminate cause and effect during the time evolution of chronic, non-communicable diseases in ageing populations. The immunogenicity of persisters, and their ability to induce various kinds of inflammation, must be rather different from that of replicating organisms, and this must be investigated. Armed with such collective knowledge, we might be better placed to develop therapeutics such as pre- and probiotics and bactericidal antibiotics for use in such cases previously thought to lack a microbial contribution.

http://femsre.oxford...sre.fuv013.full

[xEva]

This is a good paper. Thanks for posting it.

It has long been my view that modern medicine does not recognize 'benign', slowly progressing infections (unlike the acute, fumigant ones, which quickly kill or steadily lead to obvious pathology). Here the authors stress that patients with Parkinson's or Alzheimer's have far greater numbers of bacteria in their blood -- this is in addition to the numerous studies that found correlation with some viruses. I've long believed that slow but steady colonization of the body by various microbes is the major force behind the diseases of aging.

Take senescent cells for example. One of the survival strategies of the intracellular pathogens is to jam autophagy in the cells they infect -- since xenophagy (a form of autophagy that deals with intracellular pathogens) is the cells' first line of defense against them. Certain metabolites of such pathogens prevent the autophagosomes --in which they essentially live-- from maturing or merging with lysosomes, since this would complete the autophagy multistep process meant to destroy them. This constant jamming of autophagy leads to accumulation of junk in such an infected cell, which, naturally, interferes with its optimal functioning and eventually leads to emergence of a 'senescent' phenotype.

The other well-known survival strategy of intracellular pathogens is to prevent the cell they occupy from committing apoptosis. Such 'unable to die' cells are known to continuously emit inflammatory signals, apparently meant to summon specialized white blood cells to take them out. These proinflammatory signals are also known to contribute to the dysfunction of the nearby cells -- but who is to say that this is not a mere spread of the infection?

Then comes the question of amyloid deposits. There is a growing contention that these are the accumulations of antimicrobial peptides, iow these are the consequences of the innate immune response to the presence of microbes (or even their metabolites). Unlike antibodies, antimicrobial peptides are not specific to a given microorganism but instead deal with their classes -- which explains how different species of microbes can lead to essentially the same pathology (in spite of the Koch's postulate).

Downregulation of autophagy, inhibition of apoptosis, accumulation of senescent cells, rampant inflammation, intra- and extracellular amyloid deposits -- are these the hallmarks of aging or the signs of invasion by microbes? Such stealthy, slowly growing infections gradually dysregulate the whole organism. Here the prokaryotes play an active role of agents of entropy in the complex biological systems.

The main advantage of this view is that it eliminates many troubling questions that plague the prevalent aging theories, such as, for example, why would nature invent ways of killing an organism by programmed aging, or why would not natural selection take some 'defective' genes/immune responses out of a population sooner, etc. The dynamics here are simple: two vastly different life forms struggle to survive in the same living space. In this view, the animals with negligible senescence simply have superior immune systems.


So I wonder how long it will take for the mainstream to recognize the role that microbes play in aging. ..or even in diseases of aging. The history of germ theory of disease and the original resistance to it by the establishment is not encouraging. Besides, now the old entrenched idea of one microbe = one disease hinders acceptance of the broader view of how prokaryotes interact with metazoa. Specifically, what's currently lacking is the proper appreciation of the lack of specificity of the innate immune responses -- i.e. the fact that they are not a given microbe-specific but rather address a group or a whole class of microbes. This implies that a slow and steady colonization by different microbes can lead to the emergence of a similar pathology.


P.S.
I anticipate someone, for the gazillionth time, to bring up the rats reared in 'pathogen-free environment'. As the OP paper states, for ages, the key criterion used to be the culturability (according to Koch's postulates) and yet the vast majority of microbes are currently unculturable -- which, however, does not mean that they are not there, as the new, higher-technology methods amptly demonstrate.

Edited by xEva, 30 May 2015 - 07:38 PM.

[RWhigham]

Some years ago (about 1990) I acquired an excellent dark field microscope made by the original Carl Zeiss factory located in Jena, Germany. I looked at things just as a hobby.

 

I looked at numerous blood samples taken by finger prick from myself and family members. After the live erythrocytes were exposed to the microscope light for a few minutes, (using a properly adjusted dark field and an oil immersion lens) I always saw "threads" wiggling their way out of many of them.

 

According to the Livingston-Wheeler cancer clinic located in San Diego at that time, these bacteria are symbiotic to humans, but some can cause illness, and when they emerge from the erythrocytes quickly it's an indication that you are at high risk for cancer and/or heart disease. In healthy people it supposedly takes longer for them to emerge.

 

I never knew how to judge the length of time to emerge. I was just surprised to see that my red blood cells and those of other people I checked were always loaded with these wigglers which became visible as they emerged.

[Ark]

This is a good paper. Thanks for posting it.

It has long been my view that modern medicine does not recognize 'benign', slowly progressing infections (unlike the acute, fumigant ones, which quickly kill or steadily lead to obvious pathology). Here the authors stress that patients with Parkinson's or Alzheimer's have far greater numbers of bacteria in their blood -- this is in addition to the numerous studies that found correlation with some viruses. I've long believed that slow but steady colonization of the body by various microbes is the major force behind the diseases of aging.

Take senescent cells for example. One of the survival strategies of the intracellular pathogens is to jam autophagy in the cells they infect -- since xenophagy (a form of autophagy that deals with intracellular pathogens) is the cells' first line of defense against them. Certain metabolites of such pathogens prevent the autophagosomes --in which they essentially live-- from maturing or merging with lysosomes, since this would complete the autophagy multistep process meant to destroy them. This constant jamming of autophagy leads to accumulation of junk in such an infected cell, which, naturally, interferes with its optimal functioning and eventually leads to emergence of a 'senescent' phenotype.

The other well-known survival strategy of intracellular pathogens is to prevent the cell they occupy from committing apoptosis. Such 'unable to die' cells are known to continuously emit inflammatory signals, apparently meant to summon specialized white blood cells to take them out. These proinflammatory signals are also known to contribute to the dysfunction of the nearby cells -- but who is to say that this is not a mere spread of the infection?

Then comes the question of amyloid deposits. There is a growing contention that these are the accumulations of antimicrobial peptides, iow these are the consequences of the innate immune response to the presence of microbes (or even their metabolites). Unlike antibodies, antimicrobial peptides are not specific to a given microorganism but instead deal with their classes -- which explains how different species of microbes can lead to essentially the same pathology (in spite of the Koch's postulate).

Downregulation of autophagy, inhibition of apoptosis, accumulation of senescent cells, rampant inflammation, intra- and extracellular amyloid deposits -- are these the hallmarks of aging or the signs of invasion by microbes? Such stealthy, slowly growing infections gradually dysregulate the whole organism. Here the prokaryotes play an active role of agents of entropy in the complex biological systems.

The main advantage of this view is that it eliminates many troubling questions that plague the prevalent aging theories, such as, for example, why would nature invent ways of killing an organism by programmed aging, or why would not natural selection take some 'defective' genes/immune responses out of a population sooner, etc. The dynamics here are simple: two vastly different life forms struggle to survive in the same living space. In this view, the animals with negligible senescence simply have superior immune systems.


So I wonder how long it will take for the mainstream to recognize the role that microbes play in aging. ..or even in diseases of aging. The history of germ theory of disease and the original resistance to it by the establishment is not encouraging. Besides, now the old entrenched idea of one microbe = one disease hinders acceptance of the broader view of how prokaryotes interact with metazoa. Specifically, what's currently lacking is the proper appreciation of the lack of specificity of the innate immune responses -- i.e. the fact that they are not a given microbe-specific but rather address a group or a whole class of microbes. This implies that a slow and steady colonization by different microbes can lead to the emergence of a similar pathology.


P.S.
I anticipate someone, for the gazillionth time, to bring up the rats reared in 'pathogen-free environment'. As the OP paper states, for ages, the key criterion used to be the culturability (according to Koch's postulates) and yet the vast majority of microbes are currently unculturable -- which, however, does not mean that they are not there, as the new, higher-technology methods amptly demonstrate.

In studies patients with Alzheimer's, have immune systems that are attacking the brain. That being stated, the increase in microbes noted, could be the result of the haywire immune system and the result being uncommon infections or and a tendency for yeast/fungal infections as the body fights itself.

[Psilociraptor1]

This is a good paper. Thanks for posting it.

It has long been my view that modern medicine does not recognize 'benign', slowly progressing infections (unlike the acute, fumigant ones, which quickly kill or steadily lead to obvious pathology). Here the authors stress that patients with Parkinson's or Alzheimer's have far greater numbers of bacteria in their blood -- this is in addition to the numerous studies that found correlation with some viruses. I've long believed that slow but steady colonization of the body by various microbes is the major force behind the diseases of aging.

Take senescent cells for example. One of the survival strategies of the intracellular pathogens is to jam autophagy in the cells they infect -- since xenophagy (a form of autophagy that deals with intracellular pathogens) is the cells' first line of defense against them. Certain metabolites of such pathogens prevent the autophagosomes --in which they essentially live-- from maturing or merging with lysosomes, since this would complete the autophagy multistep process meant to destroy them. This constant jamming of autophagy leads to accumulation of junk in such an infected cell, which, naturally, interferes with its optimal functioning and eventually leads to emergence of a 'senescent' phenotype.

The other well-known survival strategy of intracellular pathogens is to prevent the cell they occupy from committing apoptosis. Such 'unable to die' cells are known to continuously emit inflammatory signals, apparently meant to summon specialized white blood cells to take them out. These proinflammatory signals are also known to contribute to the dysfunction of the nearby cells -- but who is to say that this is not a mere spread of the infection?

Then comes the question of amyloid deposits. There is a growing contention that these are the accumulations of antimicrobial peptides, iow these are the consequences of the innate immune response to the presence of microbes (or even their metabolites). Unlike antibodies, antimicrobial peptides are not specific to a given microorganism but instead deal with their classes -- which explains how different species of microbes can lead to essentially the same pathology (in spite of the Koch's postulate).

Downregulation of autophagy, inhibition of apoptosis, accumulation of senescent cells, rampant inflammation, intra- and extracellular amyloid deposits -- are these the hallmarks of aging or the signs of invasion by microbes? Such stealthy, slowly growing infections gradually dysregulate the whole organism. Here the prokaryotes play an active role of agents of entropy in the complex biological systems.

The main advantage of this view is that it eliminates many troubling questions that plague the prevalent aging theories, such as, for example, why would nature invent ways of killing an organism by programmed aging, or why would not natural selection take some 'defective' genes/immune responses out of a population sooner, etc. The dynamics here are simple: two vastly different life forms struggle to survive in the same living space. In this view, the animals with negligible senescence simply have superior immune systems.


So I wonder how long it will take for the mainstream to recognize the role that microbes play in aging. ..or even in diseases of aging. The history of germ theory of disease and the original resistance to it by the establishment is not encouraging. Besides, now the old entrenched idea of one microbe = one disease hinders acceptance of the broader view of how prokaryotes interact with metazoa. Specifically, what's currently lacking is the proper appreciation of the lack of specificity of the innate immune responses -- i.e. the fact that they are not a given microbe-specific but rather address a group or a whole class of microbes. This implies that a slow and steady colonization by different microbes can lead to the emergence of a similar pathology.


P.S.
I anticipate someone, for the gazillionth time, to bring up the rats reared in 'pathogen-free environment'. As the OP paper states, for ages, the key criterion used to be the culturability (according to Koch's postulates) and yet the vast majority of microbes are currently unculturable -- which, however, does not mean that they are not there, as the new, higher-technology methods amptly demonstrate.

 

I want to give you a big fat fucking kiss. People act like I'm insane when I refer to this stuff, but the vast majority of diseases faced in first world countries are better explained by infectious processes. I live for papers like this and it blows my mind how this stuff doesn't catch on.

 

As you say intracellular parasites use redundant mechanisms of inhibiting the destruction of damaged and infected cells via inhibition of apoptosis and various forms of cell-mediated immunity. I am convinced that this process is central to cancer development and is far more sensible than the immunoediting theory currently in place. Add to that the inflammatory environment needed for proliferation, angiogenesis, chemotaxis etc and the organisms liberal use of MMPs to navigate the ECM and it seems almost silly to consider this a clonal darwinian selection processes.

 

As for the amyloid deposits, i posted this on the big alzheimers thread this morning. Amyloids are not just antimicrobial peptides, but also foundational components of microbial biofilms. There is a lot of work done by Miklossy and Alan MacDonald on borrelia and treponema biofilms/infections in AD patients. I do wonder what the relationship is between the endogenous amyloids and the plaque. It is possible that microorganisms establishing residence in the brain might cross-seed their own amyloids with endogenous amyloids but that's just speculation. It is not uncommon for parasites to exploit aspects of innate immunity. But they could be just as easily separate functions. In either case the in vitro borrelia biofilm is remarkably similar to the in vivo plaque http://content.iospr...sease/jad160451

 

I actually wrote a paper for an undergrad metabolism class on the role of endotoxemia in insulin resistance, lipoprotein remodeling, tumorigenesis, the warburg effect and autoimmunity. It really just ties everything together so nice. It was actually a pretty fun piece to write and I would love to clean it up and make it public sometime. Understanding microbes has increased my understanding of human disease exponentially. Unfortunately most people think that microbes are non-intelligent cells which decend in planktonic fashion and can be eradicated with antibiotics in most cases. Similarly they think that culturing and serology are reliable methods of diagnosis. None of those can be further form the truth and such has caused serious complications in research. If people understood basic microbiology as its coming to be known in the modern era a lot of confusion would be cleared up. They are really remarkably intelligent and complex creatures.

 

Anyways I'd love to keep in communication with you on this topic. It's not often I run across someone who seems so deeply in tune with this kind of research. It's a lonely world for someone with my position on health :P

 

"In studies patients with Alzheimer's, have immune systems that are attacking the brain. That being stated, the increase in microbes noted, could be the result of the haywire immune system and the result being uncommon infections or and a tendency for yeast/fungal infections as the body fights itself."

 

Read the paper I linked. I don't know if it's the best one to answer your question but it is becoming more and more evident that microbes play a causal role in this process. If that ones not satisfactory you can look through the references. Most of the references are actually from herself as shes done a lot of work on this. She's not the only one however. The more I read the more I'm convinced that the immune system does not simply disregulate. Toxins, metals, stress, etc can certainly weaken ones immune system but the sorts of complex tissue manipulations and autoreactivity seen in things like cancers and autoimmunity and neurodegenerative disorders should really be suspected to have an infectious element.

[Kalliste]

Nevar forget Craig Venters epic ocean crusie. They found entire domains of life that were previously unknown.

 

Most previous knowledge has come from only 1% of existing micro-organisms that can be maintained or cultivated in a lab.

 

http://news.bbc.co.u...ure/6474539.stm

 

 

For this new study, Eisen, an evolutionary biologist, scanned the DNA Venter had collected for the genes found in all known organisms. But he discovered something surprising: versions that did not fit in with any of the known domains of life. It is possible that the novelty of these genes is the result of some unusual accelerated rate of evolution. But more tantalising is the possibility that they are from a previously unknown domain.

http://www.telegraph...ee-of-life.html

[sunshinefrost]

i have mold sensitivity and this makes worry a bit. 

 

i'm in my late thirties. any suggestion on how to erradicate this from the body ? cyprilic acid, pro-biotics, alkaline or keto diet ?