Abstract
We have recently highlighted (and added to) the considerable evidence that blood can contain dormant bacteria. By definition, such bacteria may be resuscitated (and thus proliferate). This may occur under conditions that lead to or exacerbate chronic, inflammatory diseases that are normally considered to lack a microbial component. Bacterial cell wall components, such as the endotoxin lipopolysaccharide (LPS) of Gram-negative strains, are well known as potent inflammatory agents, but should normally be cleared. Thus, their continuing production and replenishment from dormant bacterial reservoirs provides an easy explanation for the continuing, low-grade inflammation (and inflammatory cytokine production) that is characteristic of many such diseases. Although experimental conditions and determinants have varied considerably between investigators, we summarise the evidence that in a great many circumstances LPS can play a central role in all of these processes, including in particular cell death processes that permit translocation between the gut, blood and other tissues. Such localised cell death processes might also contribute strongly to the specific diseases of interest. The bacterial requirement for free iron explains the strong co-existence in these diseases of iron dysregulation, LPS production, and inflammation. Overall this analysis provides an integrative picture, with significant predictive power, that is able to link these processes via the centrality of a dormant blood microbiome that can resuscitate and shed cell wall components.
Highlights
Blood is normally considered a sterile environment in the sense of lacking active microbes, since any bacteraemia or sepsis is potentially extremely life-threatening.[1]
This does not exclude the presence in blood of dormant bacteria, that by definition[2,3] are not growing but resist detection by standard culture techniques, yet are not ‘dead’ as they may be resuscitated
We have recently summarised the considerable evidence[4,5] to the effect that human blood contains an authentic but dormant microbiome that can contribute significantly to a large variety of chronic inflammatory diseases, a set of diseases that is strikingly similar to those for which we had previously noted the presence of iron dysregulation[6,7,8,9,10] and hypercoagulability.[9]
Summary
Blood is normally considered a sterile environment in the sense of lacking active microbes, since any bacteraemia or sepsis is potentially extremely life-threatening.[1]. 22 and 23), such an analysis leads to the recognition that the iron-related inflammatory diseases have a major microbial component involving the resuscitation of dormant organisms and their shedding of inflammatory molecules, and especially of cell wall components such as LPS (Fig. 1).
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