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Note: following changes at Bioscreen, some of the information on this page may be out of date. Check out the revised Bioscreen website for the latest information.
by Moira A Smith
This article was first written in September 1997 in response to a Reuters Report about the work of an Australian team of CFS researchers from Newcastle University. Since then, the report has been clarified by presentations at the Sydney CFS Conference in February 1998, and information on the CPRUIS (Newcastle University) website. This is a revised version.
See also the Bioscreen Information Service website.
Contents
Introduction
The role of intestinal bacteria in our health
The immune connection
Leaky gut syndrome
Gut bugs and other CFS symptoms
Conclusion
References
This article is based on my understanding of work of the Newcastle research team and other scientists and practitioners with expertise in CFS. Please go to the source material for authoritative information. I am not a doctor, biochemist, or indeed scientist of any kind, and can only give a layperson's interpretation.
But I take heart from what Associate Professor Tim Roberts (one of the Newcastle researchers) told a CFS support group in May 96. He said that the first positive step a person afflicted with CFS (and that means fibromyalgia too) can take is to learn as much as possible about the illness [1]. He reminded his listeners that many people who have written books about CFS and become experts in the disease are themselves sufferers, and don't necessarily have medical backgrounds:
People with CFS need to become their own experts so that they in turn can educate their doctors and the community.
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In September 1997, a news report from Australia [5] provoked discussion and questions on CFS newsgroups and mailing lists on both sides of the world. Entitled Commensal Bacteria Linked To Chronic Fatigue Syndrome, it announced:
Australian scientists believe that they have the evidence to prove that the debilitating symptoms of chronic fatigue syndrome (CFS) are the result of infection by otherwise harmless commensal bacteria and subsequent changes in bacteria of the gut.
Associate Professor Timothy K. Roberts and his colleagues Neil R. McGregor, R. Hugh Dunstan, Mariann Zerbes, Henry L. Butt, Iven Klineberg and others at the University of Newcastle's Collaborative Pain Research Unit (CPRU) have been working on the problem of CFS since 1992 ...
The report gave some background to the work of the Newcastle team and went on to quote Dr. Tim Roberts as saying:
"The concept is that overall it's the change in the bacterial flora that leads to the secondary problems that people get with CFS."
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When this press release came out people started asking, just how could a "change in the bacterial flora" cause CFS symptoms? I had been aware in a vague sort of way that bacteria live inside us and were somehow important for our health. While I had previously found the idea rather off-putting, I now became interested in finding out more.
I found a useful explanation of the role of these "friendly bacteria" in an article by Leon Chaitow:
Inside each of us live vast numbers of bacteria without which we could not stay alive in good health ... There are several thousand billion in each of us (more than all the cells in your body!) divided into over 400 species, most of them living in your digestive tract.
These bacteria are not parasites. They do not just take up residence and do nothing in return ... indeed they pay their way handsomely. We live in true symbiosis with them. [6]
The author goes on to list the many things they do, including making vitamins and lactase (the milk-digesting enzyme), and deactivating many toxic pollutants.
Normally, our gut bacteria look after themselves - it seems that "the microbial flora of an individual is very consistent" despite changes of diet. However some events, including stress, anxiety, the presence of parasitic organisms, and the use of antibiotics can change the balance [7], as can taking NSAIDs (non-steroidal anti-inflammatory drugs) [8].
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When I read the news report about the "commensal bacteria" having an effect on CFS symptoms, I was at first at a loss to see how this could fit in with other theories I had read about CFS. I particularly wondered about the link with the immune system, as I knew many CFS experts believe that immune dysfunction is involved (hence the alternative name Chronic Fatigue and Immune Dysfunction Syndrome - CFIDS). For example, Dr Paul Cheney has stated that:
there is an ever increasing body of scientific evidence which supports a coherent pathophysiologic view of CFS as an immune dysregulatory state with associated neurologic and metabolic dysfunction [9].
Cheney and others conjecture that CFS is characterised by a chronic "up-regulation" or over-stimulation of the immune system. According to this theory, the over-stimulation of the immune system is what makes us feel fluey and fatigued, just the way we feel when we are fighting off an infection. The particular culprits may be cytokines - chemicals produced by the immune system when it is activated:
... the signs and symptoms of CFS can be explained as a consequence of immunologic function or dysfunction. Fever, sore throat, swollen glands, aching muscles and joints, sleep disturbance, and even neuropsychological complaints can all be attributed to immunologic responses generally ascribed to T-cell activation with excess cytokine production ... Whether this excessive immune response is itself the cause (auto-immune or neuroendocrine defects) of CFS or perhaps the effect of a chronic viral infection or even compensation, by whatever means, for an acquired immune deficiency remains uncertain. [10]
As Drs Cheney and Lapp point out above, it is not known what might cause this immune response, although there are many theories: it could be due to a viral or bacterial infection, either ongoing or as the trigger which first activated the immune system. Many different viruses have been implicated in the past eg Epstein-Barr, Cocksackie, Borna, or even a monkey virus that at one time contaminated some batches of polio vaccine. Currently, Dr Garth Nicolson's work is focussing on mycoplasma as the infecting agent, while Dr John Martin claims to have identified a "stealth virus". Another possibility is that environmental toxins or other biological stressors (illnesses or accidents) could trigger the immune system. It is likely that the trigger is different in different people, because there is almost certainly more than one kind of CFS [11].
It is not too difficult to work out why immune system overactivation could impact on other functions of the body. One effect is described by Prof. John Dwyer, the Sydney CFS researcher and doctor, in his book "The Body at War: the story of our immune system" (1988):
Normal tissue is damaged by the constantly high concentration of chemicals meant to be present in tissues for only a brief period. If you examine the side effects of interferon, a T-cell product normally released transiently in the course of an infection but now available for therapeutic purposes, the side effects associated with too high a dose are very similar to CFS.
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The theory of the "Leaky Gut Syndrome" - "clinical disorders associated with increased intestinal permeability," and including CFS [8] provides a link between the immune system and intestinal flora. Actually our intestines are supposed to be somewhat "leaky", to let the nutrients from the food we eat pass through into our bodies. Dr Gary Deed has explained that the phenomenon is easier to understand as the "Extra-Leaky" Gut Syndrome [12], and he describes it as follows:
Our normal bacteria protect a layer of special cells that line the gut. These cells fit together quite tightly, so that only the small molecules of digested food can slip between them ...
If an overgrowth of harmful bacteria proliferates at the expense of our natural intestinal flora - perhaps after an antibiotic has killed some of them off (as weeds will grow in a cleared patch of soil where a plant has been pulled out), or through stress or other causes - these unnatural bacteria can damage the lining of the gut, so that the wrong kind of - and too large - molecules get through:
You normally only absorb nutritious, digested molecules of food as a protection to the body. Something goes and disorders this protective mechanism, the gut becomes leaky, you absorb products that you don't necessarily need. They stimulate the immune system which lines the gut...
An imbalance of intestinal flora is called "dysbiosis" -- "... a state in which disease or dysfunction is induced by organisms of low intrinsic virulence that alter the metabolic or immunologic responses of their host" [8]. As a result of this dysbiosis, the CFS sufferer's intestines are "overleaky", leading to the body absorbing harmful (instead of nutritious) substances, or incompletely digested food. Not only that, but the immune system cells lining the gut are affected.
Leaky Gut Syndrome caused by abnormal gut flora can result in toxins being released into the blood stream, and vitamin and other deficiencies. In addition, because of the immune system being stimulated by undigested food particles, food sensitivities can develop, adding to the CFS sufferer's symptoms [8].
Dr Mark Donohoe, one of Australia's best known medical practitioners in the fields of CFS and environmental medicine, says that identifying food sensitivities and restoring normal bowel flora are important factors in treating CFS [13].
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It was actually at a Canberra seminar by the Newcastle research team in February 1997 [14] that I first heard gut bacteria mentioned in the context of CFS. Some of the anomalies the team had found in their CFS subjects at that stage indicated changes in the gut flora that process lipids.
Since then the continuing research at Newcastle has brought to light another way in which the gutbugs can cause CFS symptoms. The Newcastle scientists have confirmed that intestinal flora are abnormal in people with CFS [15]. In addition, there is now evidence of a relationship between that abnormality and the unusual amounts of amino and organic acids in the urine of CFS people ... and that relationship may be a very direct one:
... preliminary results suggest that at least certain bacterial species in the gastrointestinal tract can contribute to the nutrition of the host by providing non-essential and essential amino acids, as well as other growth factors. Considering the microbial mass within the colon, this could represent a very significant contribution to the nutrition of the human host. [7]
Research at Newcastle has shown that CFS patients have "marked alterations of the fecal microbial flora" [16] including low amounts of E.Coli. The Newcastle scientists have been investigating the role of E.Coli and other gut bacteria in nutrition, and the three species they have looked at so far have all turned out to be able to produce amino and organic acids. So this may explain why people with CFS are often lacking in these substances [15].
In particular, gut bacteria can produce serine and the serine precursors alanine and glycine. Changes in the gut flora appear to be associated with the low serine output already noted to be "an important factor contributing to the severity of symptoms in patients with CFS" [16].
There is now also a suggestion from Newcastle and elsewhere that toxins produced by bacteria present in abnormal quantities in the gut and other places in the body can be a cause of muscle pain in CFS [15, 17]. (See the article on Staphylococci and CFS/FM on this website for more information and references.)
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It seems likely that for some of us, management of food sensitivities and treatments to restore a normal balance of intestinal bacteria - for example by taking acidophilus and other "friendly" gut bugs in supplements or yoghurt - can lead to an easing of some of our symptoms. This is not a cure, as it is probably not addressing the problem that made us sick in the first place, but it offers hope for improving our general condition.
It is not a new idea, and it is interesting that the Newcastle research has given more evidence and suggestions about how things are going wrong, and why doing something about gut function can be a really important part of any CFS treatment protocol.
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from the 2001 Sydney Conference:
'Bacterial Colonosis' in Patients with
Persistent Fatigue
1. Talk to the Victorian CFS/ME Society, reported in Emerge magazine June 96.
References 2-4 have been moved to another article together with the associated text
5. "Commensal Bacteria Linked To Chronic Fatigue Syndrome", Sydney Sep 09 1997; Copyright © Reuters Health.
6. "Probiotics: The Friendly Bacteria" by Leon Chaitow N.D., D.O., MRO, Senior Lecturer, University of Westminster
7. "Faeces - Biochemical and Microbiological Aspects" [cpruis/Faeces.html] - formerly on the CPRUIS (Newcastle University) website .
8. Leaky Gut Syndromes: Breaking the Vicious Cycle by Leo Galland, M.D., from HealthWorld Online
9. Cheney Clinic Information Service CFS FAQ
10. Paul R. Cheney, MD, PhD and W. Charles Lapp, MD, FAAP, The Diagnosis of Chronic Fatigue Syndrome: An Assertive Approach
11. "Homeostatic heterogeneity in CFS Patients" by Hugh Dunstan [Htalk98.htm] - formerly on the CPRUIS (Newcastle University) website
12. Dr Gary Deed, speaking to the Queensland ME/CFS Society 25 May 96, as reported in their newsletter.
13. Mark Donohoe, "Chronic Fatigue Syndrome: Bringing it all together" at Dr Mark Dohohoe's InfoCentre
14. Public presentation by Assoc. Prof. Tim Roberts and Dr Neil McGregor, sponsored by the ACT ME/CFS Society Inc. and the ACT Division of the Royal Australian College of General Practitioners; Canberra, 18 Feb 1997.
15. Alteration of the Bacterial Microbial Flora in Chronic Fatigue/Pain Patients by HL Butt, RH Dunstan, N R McGregor, T K Roberts, M Zerbes, and I J Klineberg
16. Slide show on "Urinary serine and changes in the faecal microflora" [cpruis/1Micro98/index.htm] - formerly on the CPRUIS (Newcastle University) website
17. Carl Gottfries : "Effects of Staphylococcus Toxoid in Patients with Fibromyalgia and Chronic Fatigue Syndrome." (abstract of paper delivered at the 1998 Sydney conference, on the AHMF website)
Moira Smith 1997, revised version Nov 1998
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Moira A Smith - Canberra, Australia
last revised 21 Feb 2004