A link between a single molecule from a bacterial cell wall component, which can lead to the anomalous behaviour of 100m clotting molecules, and diseases such as Alzheimer's, Parkinson's and diabetes has been made by a collaboration between the University of Pretoria and the University of Manchester.
The discovery could help to explain many features of these kinds of diseases, and may lead to new methods of prevention or treatment.
A team from South Africa, lead by Professor Resia Pretorius and including student, Sthembile Mbotwe, and researcher, Dr Janette Bester, together with colleagues from University of Manchester, under leadership of Professor Douglas B Kell, tested blood and plasma for its ability to clot when the normal clotting agent thrombin was added.
Normal, healthy blood clots have a nice spaghetti-like appearance. However, the results showed that tiny amounts of cell wall molecules such as lipopolysaccharide (LPS), which are shed by dormant bacteria, caused a highly anomalous clot to form dense deposits with very different fibres.
These can contribute to the chronic inflammation that is part of many supposedly non-infectious diseases. These include Alzheimer’s, Parkinson’s, auto-immune conditions such as rheumatoid arthritis, cardiovascular problems such as stroke, and metabolic diseases including type 2 diabetes.
Impact on treatment
The discovery could have considerable impact on the treatment of these conditions, since stopping the unusual clotting would be expected to stop its consequences. Existing treatments do not so this as the new mechanism had not previously been known.
Pretorius says: “The importance of LPS in inflammatory diseases has been mostly overlooked, and has been used to induce both Alzheimer's and Parkinson's disease in animal testing for many years. Inflammatory diseases are also closely linked to leaky gut syndrome. Together with our new findings regarding the involvement of a (dormant) blood microbiome, this demonstrates that dormant bacteria can play an important role in all inflammatory diseases.”
“The breakthrough finding that tiny amounts of bacterial cell wall material can have a massive effect on causing blood to clot in an unusual way explains much about the biology of many of these diseases. This opens up novel means ̶ including nutritional ̶ for their prevention and treatment,” explains Kell.
The work is part of an ongoing collaboration between the University of Pretoria team and The University of Manchester team, funded by the Biotechnology and Biological Sciences Research Council to understand unusual blood clotting, the National Research Foundation (South Africa) and the Medical Research Council (South Africa).