Gutted by bad gut bugs

As the year draws to an end, are you feeling tired, and run down? Do you feel like you could sleep for a week and that you’ve reached the limit of your energy? Some regular sleep and a couple of week’s beach holiday will probably revitalise you enough to start afresh in the New Year.

But what if you experience mental and physical exhaustion even after a minimal amount of exertion, such as from activities of daily living or simple mental tasks? What if your fatigue is so severe, that you have had to substantially cut down on regular work, education or social activities?

This is what people with chronic fatigue syndrome (CFS), or myalgic encephalomyelitis (ME) experience. As the name implies, ME/CFS is a chronic, often severely disabling disease that comes with a myriad of symptoms rooted from the autonomic nervous system, immune system, endocrine system and gut. People with ME/CFS commonly experience headaches, muscle and joint pain, unrefreshing sleep, irregular heartbeat, shortness of breath and problems in thinking and memory. They may not be able to regulate body temperature; and experience visual disturbances and extreme photosensitivity; balance problems; and irritable bowel, amongst others symptoms. A good night’s sleep is not going to fix their severely debilitating disorder and treatments are hard to come by. 

It is only in recent years that ME/CFS is being taken seriously by the medical and scientific community.

Despite this, some research teams have taken up the challenge and researchers at the Bio21 Institute, with little funding, have been steadily working on gathering evidence in this field.

Chris Armstrong, a researcher at the Bio21 Molecular Science and Biotechnology Institute is the lead author on some recent studies that associate metabolites and microbiota in faeces, blood and urine with ME/CFS.

Together with a clinician, Dr Donald Lewis, he has been obtaining urine, blood and faecal samples (after overnight fasting) from 34 people diagnosed with ME and from 25 people who are not affected. All participants in the study are women, as sex significantly influences results and also, because proportionally greater numbers of women are diagnosed with ME.

Utilising the extensive expertise of his supervisor, A/Prof Paul Gooley, in the use of magnetic resonance spectrometry and an institute with the largest magnetic resonance facility in Australia, Chris harnessed this knowledge and tools to ask whether there were any differences in the energy metabolism of people with ME/CFS.

He ran his samples through magnetic resonance spectrometers to look for changes in the levels of the major metabolites in faeces, blood and urine; that include the amino acids, glucose, short chain fatty acids (SCFA) and organic acids.

At the heart of the problem is energy – how our body metabolises food and converts it to a usable form of energy. Another part of the equation is our commensals; the bacteria in our gut, that also gain energy from our food.  

Building on his lab’s previous work, that found altered gut bacterial populations in patients suffering from ME/CFS, Armstrong, published findings showing changes of metabolites in the blood and urine of ME/CFS patients. These changes hinted at a slight, but significant shift in the body’s source of energy production: from sugars to amino acids. Also, Armstrong observed that biochemical pathways associated with cell and tissue damage as a result of oxidative stress were more active. -

The complexity of ME/CFS, means that by its nature, the research spans a number of disciplines, particularly metabolomics, microbiology and immunology. Both Armstrong’s studies have been ground-breaking across these disciplines.

The results from his most recent publication confirm differences in gut microbiota in people with ME/CFS across blood, urine and faecal biofluids, as well as elevated levels of short-chained fatty acids (SCFA) at the expense of amino acids, due to more fermentation taking place in the gut of ME/CFS patients.

Working together with Dr Neil McGregor and Dr Henry Butt, Bioscreen, Chris wanted to see whether there were correlations between his observations in metabolism in his samples and the presence of certain types of bacteria.

As suspected, Chris found that not only were there differences in the energy metabolism of people with ME/CFS, but that these are correlated to their gut microbiota.

How can the bacteria in the gut be making people feel tired?

It’s early days, but the research is hinting that the composition of the gut bacterial populations (good gut guys vs bad gut guys) could be skewing the body’s metabolism away from obtaining energy from glucose in the process of glycolysis (glucose to energy), to gaining energy from fats and proteins.

This is akin to what our body does when it is starving and it may be a possible explanation for the lack of energy people have in ME/CFS.

More research needs to be done on how the energy metabolism pathways of our body (i.e. citric acid cycle) can be affected by gut bacteria.

“ME/CFS is a complex condition and to find the answer, we need to take a whole-body approach,” argues Chris. “And the new knowledge gained in metabolomics and systems biology, will make it possible to delve into the complexity of our body’s metabolism.”

By Florienne Loder

christopher.armstrong [at] unimelb.edu.au (Chris Armstrong is available for media comment.)