- Email: [email protected]
Do blood bacteria cause many ills?
THIS WEEK
Debora MacKenzie
COULD bacteria be to blame for a host of conditions we thought had nothing to do with infection? A molecule made only by bacteria has been found to change blood proteins in a way that is common to a score of “non-infectious” conditions, from heart attacks to Alzheimer’s disease. All involve inflammation, abnormal blood clotting, excessive iron in the blood and sheets of abnormally folded
“The role of infection in neurodegenerative disorders has been underexplored” proteins. If bacteria really link all these observations, we might find that it’s possible to fight these “non-infectious” illnesses by attacking the microbes. Healthy blood has always been considered sterile, because bacteria don’t grow when blood is put in a culture dish. But recent DNA sequencing methods reveal that each millilitre of blood in fact contains around 1000 bacteria. These bacteria are usually dormant, says Douglas Kell at the University of Manchester, UK. They need iron ions to grow, and iron is bound up by proteins that keep free ions at vanishingly low levels in our blood. But the bacteria can be revived when iron levels climb for some reason, whereupon they secrete molecules on their cell walls called lipopolysaccharides (LPS). These are recognised by the immune system and stimulate inflammation – a general activation of the immune system that normally helps fight infection, but can get out of control and cause damage. 8 | NewScientist | 17 September 2016
Kell and his colleague Resia Pretorius at the University of Pretoria in South Africa wondered if LPS might be involved with the abnormal blood clotting often seen in diseases involving inflammation. Most bacteria in our blood come from our gut. So they mixed LPS from Escherichia coli gut bacteria with fibrinogen, the blood protein that forms the fibrin scaffolds of clots. The LPS bound to fibrinogen, and made it form abnormal, matted clots. Just one molecule of LPS mixed with 100 million fibrinogen molecules was enough to trigger these changes (Journal of the Royal Society Interface, doi.org/bqh5). Kell thinks LPS makes the protein take on a sheet structure rather than a helix, and this deformation then spreads between fibrinogens, in a similar way to how the deformation in prion proteins spreads to cause BSE. The abnormal clots closely resembled the ones that cause
KATERYNA KON/SPL
Do blood bacteria cause many ills?
–Not so sterile–
heart attacks and strokes – but they are also seen in other inflammatory diseases that don’t obviously involve clotting (see “From heart attacks to diabetes”). “In all inflammatory conditions we have noted a matted, denser fibrin structure, without the
FROM HEART ATTACKS TO DIABETES Microbes in the blood – and the inflammation they can cause when the immune system fights back – could be a contributing factor in all sorts of conditions not usually linked with bacteria (see main story). The risk of heart attack, diabetes, stroke and rheumatoid arthritis is higher in people with gum disease – which provides bacteria with an easy route into the blood. These conditions all share the hallmarks of bacteria. There is evidence that bacteria help form “amyloid” mats in the brain, like those in people with Alzheimer’s and Parkinson’s disease. Injecting bacteria directly into mouse brains causes amyloid plaques to form
overnight, for example. And the more bacteria-nourishing iron in your brain, the more likely you are to get Alzheimer’s. Conversely, people with lower levels of iron in their blood have a lower risk of heart attack. There could potentially be a link to cancer, too. Inflammation is seen in cancer and the anti-inflammatory drug aspirin is known to lower cancer rates. The pill is also reported to bind free iron, which together may suggest bacteria have a hidden role in this disease too. In the past few years, inflammation has been tantalisingly linked to mental health disorders, such as schizophrenia, bipolar disorder and depression.
typical ‘spaghetti structure’ found in healthy individuals,” says Pretorius. “We think bugs are involved in all these diseases,” says Kell. The work “certainly merits further investigation”, says Joanna Collingwood at the University of Warwick in the UK, who studies metals in Alzheimer’s disease. “The role of infection in neurodegenerative disorders has been underexplored in the past.” It is an “interesting new development” if LPS can cause clot structures similar to those seen in chronic diseases, says Mike Barer at the University of Leicester, UK. What needs further investigation, he says, is whether dormant bacteria in blood really play a role. If they do, though, drugs that stop the effects of these bacteria might prove useful against major killers like heart attacks, strokes and even Alzheimer’s. Just giving patients drugs that mop up free iron might help. Kell wants to try such “chelators” in people at risk of stroke. n
Debora MacKenzie
COULD bacteria be to blame for a host of conditions we thought had nothing to do with infection? A molecule made only by bacteria has been found to change blood proteins in a way that is common to a score of “non-infectious” conditions, from heart attacks to Alzheimer’s disease. All involve inflammation, abnormal blood clotting, excessive iron in the blood and sheets of abnormally folded
“The role of infection in neurodegenerative disorders has been underexplored” proteins. If bacteria really link all these observations, we might find that it’s possible to fight these “non-infectious” illnesses by attacking the microbes. Healthy blood has always been considered sterile, because bacteria don’t grow when blood is put in a culture dish. But recent DNA sequencing methods reveal that each millilitre of blood in fact contains around 1000 bacteria. These bacteria are usually dormant, says Douglas Kell at the University of Manchester, UK. They need iron ions to grow, and iron is bound up by proteins that keep free ions at vanishingly low levels in our blood. But the bacteria can be revived when iron levels climb for some reason, whereupon they secrete molecules on their cell walls called lipopolysaccharides (LPS). These are recognised by the immune system and stimulate inflammation – a general activation of the immune system that normally helps fight infection, but can get out of control and cause damage. 8 | NewScientist | 17 September 2016
Kell and his colleague Resia Pretorius at the University of Pretoria in South Africa wondered if LPS might be involved with the abnormal blood clotting often seen in diseases involving inflammation. Most bacteria in our blood come from our gut. So they mixed LPS from Escherichia coli gut bacteria with fibrinogen, the blood protein that forms the fibrin scaffolds of clots. The LPS bound to fibrinogen, and made it form abnormal, matted clots. Just one molecule of LPS mixed with 100 million fibrinogen molecules was enough to trigger these changes (Journal of the Royal Society Interface, doi.org/bqh5). Kell thinks LPS makes the protein take on a sheet structure rather than a helix, and this deformation then spreads between fibrinogens, in a similar way to how the deformation in prion proteins spreads to cause BSE. The abnormal clots closely resembled the ones that cause
KATERYNA KON/SPL
Do blood bacteria cause many ills?
–Not so sterile–
heart attacks and strokes – but they are also seen in other inflammatory diseases that don’t obviously involve clotting (see “From heart attacks to diabetes”). “In all inflammatory conditions we have noted a matted, denser fibrin structure, without the
FROM HEART ATTACKS TO DIABETES Microbes in the blood – and the inflammation they can cause when the immune system fights back – could be a contributing factor in all sorts of conditions not usually linked with bacteria (see main story). The risk of heart attack, diabetes, stroke and rheumatoid arthritis is higher in people with gum disease – which provides bacteria with an easy route into the blood. These conditions all share the hallmarks of bacteria. There is evidence that bacteria help form “amyloid” mats in the brain, like those in people with Alzheimer’s and Parkinson’s disease. Injecting bacteria directly into mouse brains causes amyloid plaques to form
overnight, for example. And the more bacteria-nourishing iron in your brain, the more likely you are to get Alzheimer’s. Conversely, people with lower levels of iron in their blood have a lower risk of heart attack. There could potentially be a link to cancer, too. Inflammation is seen in cancer and the anti-inflammatory drug aspirin is known to lower cancer rates. The pill is also reported to bind free iron, which together may suggest bacteria have a hidden role in this disease too. In the past few years, inflammation has been tantalisingly linked to mental health disorders, such as schizophrenia, bipolar disorder and depression.
typical ‘spaghetti structure’ found in healthy individuals,” says Pretorius. “We think bugs are involved in all these diseases,” says Kell. The work “certainly merits further investigation”, says Joanna Collingwood at the University of Warwick in the UK, who studies metals in Alzheimer’s disease. “The role of infection in neurodegenerative disorders has been underexplored in the past.” It is an “interesting new development” if LPS can cause clot structures similar to those seen in chronic diseases, says Mike Barer at the University of Leicester, UK. What needs further investigation, he says, is whether dormant bacteria in blood really play a role. If they do, though, drugs that stop the effects of these bacteria might prove useful against major killers like heart attacks, strokes and even Alzheimer’s. Just giving patients drugs that mop up free iron might help. Kell wants to try such “chelators” in people at risk of stroke. n