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.
