Lipopolysaccharides coating a bacterial cell wall (top) may have an insidious role to play in disease Russell Kightly/Science Photo Library

Could microbes be to blame for a host of diseases we thought they had nothing to do with? Researchers have found that bacteria in the blood of healthy people may help trigger strokes and heart attacks, and perhaps also contribute to conditions like Alzheimer’s disease, diabetes and arthritis.

All of these disorders involve inflammation – a general activation of the immune system that normally serves to fight infection, but that can get out of control and cause damage. These conditions are also all linked to overactive blood clotting, excessive levels of iron in the blood, and sheets of abnormally folded proteins.

No one knows why these traits are linked to so many diseases, but finding out could help us stop them. To see if bacteria could be playing a role in all this, Douglas Kell at the University of Manchester, UK, and Resia Pretorius, at the University of Pretoria in South Africa, have been looking at their ability to disrupt clotting.


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Blood has always been considered free from microbes, because bacteria don’t grow when it is put in a culture dish. But recent DNA sequencing methods reveal that each millilitre of blood in fact contains around 1000 bacterial cells.

These bacteria are usually dormant. But they can be revived when iron becomes available in the blood, and begin secreting lipopolysaccharides (LPS) – molecules on their cell walls that are recognised by the immune system and stimulate inflammation.

Clotting catalyst

Kell and Pretorius wondered if LPS might also directly affect clotting. Most dormant bacteria in our blood comes from our gut. They mixed LPS from the common gut bacteria Escherichia coli with fibrinogen, a small protein in the blood that normally forms the fibrin scaffolds of clots. The LPS changed the fibrinogen, encouraging it to form abnormal clots that look a lot like those involved in heart attacks, strokes and deep vein thrombosis.

“In all inflammatory conditions we have noted a matted, denser fibrin structure, without the typical ‘spaghetti structure’ found in healthy individuals,” says Pretorius. Just one molecule of LPS in a mixture of a hundred million fibrinogen molecules was enough to encourage the formation of these misformed clots.

This means LPS must act as a catalyst, says Kell. They think LPS bends fibrinogen out of shape, and this shape-change spreads from protein to protein in a similar way to the deformation associated with prion proteins that cause BSE.

And since LPS triggers inflammation, it increases levels of fibrinogen in the blood, further raising the risk of the aberrant disease-linked clots. Because of their weird structure, these clots are also resistant to being broken down by blood enzymes. Together, these effects could be raising the risk of aberrant clotting, leading to heart attacks and strokes.

Fighting inflammation

Overactive clotting is also a feature of inflammatory conditions like rheumatoid arthritis and Alzheimer’s. These conditions involve excess levels of iron. The body normally keeps levels of free iron in the blood low to keep bacteria dormant and block their growth.

“We think bugs are involved in all these diseases,” says Kell. Their observation that LPS causes fibrin to form mats, and the fact that LPS also binds to many other proteins, could implicate it in forming the amyloid mats seen in other inflammatory diseases, such as those in in the brains of people with Alzheimer’s and Parkinson’s disease. Earlier this year, other researchers found that injecting bacteria into the brains of mice prompted them to form amyloid plaques overnight.

What does this all mean for these diseases? Further research could open up several new approaches for tackling them, from removing dormant microbes from our blood, to blocking the inflammatory proteins that they shed.

Journal reference: Journal of the Royal Society Interface, DOI: 10.1098/rsif.2016.0539