Abstract
ABSTRACTSince the successful conquest of many acute, communicable (infectious) diseases through the use of vaccines and antibiotics, the currently most prevalent diseases are chronic and progressive in nature, and are all accompanied by inflammation. These diseases include neurodegenerative (e.g. Alzheimer's, Parkinson's), vascular (e.g. atherosclerosis, pre‐eclampsia, type 2 diabetes) and autoimmune (e.g. rheumatoid arthritis and multiple sclerosis) diseases that may appear to have little in common. In fact they all share significant features, in particular chronic inflammation and its attendant inflammatory cytokines. Such effects do not happen without underlying and initially ‘external’ causes, and it is of interest to seek these causes. Taking a systems approach, we argue that these causes include (i) stress‐induced iron dysregulation, and (ii) its ability to awaken dormant, non‐replicating microbes with which the host has become infected. Other external causes may be dietary. Such microbes are capable of shedding small, but functionally significant amounts of highly inflammagenic molecules such as lipopolysaccharide and lipoteichoic acid. Sequelae include significant coagulopathies, not least the recently discovered amyloidogenic clotting of blood, leading to cell death and the release of further inflammagens. The extensive evidence discussed here implies, as was found with ulcers, that almost all chronic, infectious diseases do in fact harbour a microbial component. What differs is simply the microbes and the anatomical location from and at which they exert damage. This analysis offers novel avenues for diagnosis and treatment.
Highlights
A very large number of chronic, degenerative diseases are accompanied by inflammation
Various sequelae, including coagulopathies, amyloid formation and cell death follow from this, and we argue that this general explanation – that we refer to here as the Iron Dysegulation and Dormant Microbes (IDDM) hypothesis– underpins a host of these chronic, inflammatory diseases
It is starting to be recognised that microbes said to be adopting this state may be dormant (Oliver, 2010), we suggest that the term ‘viable-but-not-culturable’ is avoided altogether (Kell et al, 1998)
Summary
A very large number of chronic, degenerative diseases are accompanied by inflammation. These hallmarks include increased levels of inflammatory cytokines (almost a definition of inflammation), dysregulation in iron metabolism [especially the appearance of abnormal levels of ferritin in the serum (Kell & Pretorius, 2014)], and a variety of coagulopathies and haematological pathologies (abnormalities in the blood system, including its clotting properties) Many of these diseases share other properties such as an increase in ‘insoluble’ forms of normally soluble proteins and of microparticulate material. Based on a considerable and wide-ranging literature, we here bring together evidence that: (i) the main external stimuli are microorganisms; (ii) in contrast to what happens in conventional infectious diseases they do not proliferate unchecked, but commonly enter dormant states that make them invisible to classical microbiology; and (iii) they can be reactivated from these dormant states by the presence of ‘free’ iron (a necessary nutrient that in unliganded form is normally at low levels in the host).
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