Peer-reviewed Experimental Animals
An international team of scientists, led by the University of Glasgow, have announced a new advance in our understanding of how bacteria in our gut can provide positive health benefits.
The breakthrough findings, published today in Nature Chemical Biology, provide evidence that it may be possible to design drugs that will mimic these positive health benefits in a way that might be used to treat diseases such as type II diabetes.
It is known that bacteria in the gut can provide positive health benefits; however, the mechanism by which gut bacteria works has been unclear.
Scientists think one possibility is that gut bacteria, by fermenting starches in food such as oats and pulses (like beans and chickpeas), produce compounds called short chain fatty acids (SCFAs). One of these SCFA’s is acetic acid - the main component of vinegar.
Once produced, these SCFAs activate specific receptor proteins in our body and these receptors, once activated, can provide health benefits.
In a four-year study, the Glasgow team used a combination of genetics and pharmacology to ask if one of these receptor proteins – called short chain free fatty acid receptor 2 (FFA2) – when activated selectively by drugs, generated responses in the body that underpin the health benefits of gut bacteria.
Andrew Tobin, Professor of Molecular Pharmacology at the University’s Institute of Molecular Cell & Systems Biology, said: “Through a clever genetic trick, we have been able to determine firstly, that the levels of glucose in our blood and fat in our bodies can be controlled by gut bacteria. This is done via a specific receptor protein in our body, and we believe that the positive health benefits of gut bacteria can be mimicked by drugs that activate this receptor protein.”
Professor Graeme Milligan, Gardiner Chair of Biochemistry, added: “By generating a genetically-altered mouse that contains a form of FFA2 that can be activated only by a drug, we found that FFA2 can control the speed of food moving through the gut, the release of hormones that can control glucose levels and the release of fat from fat tissue.”
The scientists believe that, not only can FFA2, which is normally activated by acetic acid generated by gut bacteria, control these key processes important for our health and well-being but, importantly, that this receptor protein could be a target for new drugs in diseases where our response to food intake is dysfunctional, such as in type II diabetes.
Prof Tobin said: “This is a major advance in our understanding our how our bodies respond to food and how the bacteria in our gut provide health benefits.
“Our study not only advances our basic understanding of how the gut microbiome works in health and well-being but also provides the framework to design drugs that can mimic the health benefits of the gut microbiome.”
“Whereas many people are trying to capture the health benefits of the gut microbiome through probiotics, our study indicates that we can bypass the bacteria in our gut and directly target our bodies’ receptors with drugs that mimic the gut bacteria to provide health benefits in diseases such as type II diabetes.”
The paper, ‘Chemogenetics defines receptor-mediated functions of short chain free fatty acids’ is published in Nature Chemical Biology. The work was funded by the Biotechnology and Biosciences Research Council (BBSRC) and the Medical Research Council (MRC).
Paper can be found here: http://dx.doi.org/10.1038/s41589-019-0270-1
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