Kynurenine Production Insufficiency In Me/cfs Patients
One of the newer research topics about the etiology of ME/CFS patients is an abnormal metabolism of tryptophan to kynurenine including its catalyst indoleamine-2, 3-dioxygenase expressed in antigen-presenting cells . The precise measurement of tryptophan and its metabolites is an interesting approach for potential biomarkers and therapies in current general research . Physiologically, the essential amino acid tryptophan is metabolized approximately 5% to serotonin and melatonin, and degraded approximately 95% by the enzyme IDO to kynurenine . IDO and the kynurenine pathway play important roles in the immune system as immunoregulators and immunosuppressors . IDO is induced by infection and inflammation through pro-inflammatory cytokines and mediators, mainly by IFN-y, but also IFN-, TNF- and LPS . Elevated IDO expressions seem to be an important hallmark of chronic viral infections such as HIV, hepatitis B and C by building an immune tolerant environment. Although elevated levels of IDO seem to correlate with the severity of diseases, the relevance of these findings remains unestablished . IDO activates regulatory T-cells and suppresses effector T-cell proliferation and function by the degradation of tryptophan to kynurenine , which enhances immunologic tolerance towards chronic infections.
Icipant Recruitment And Sample Collection
A total of 105 volunteers were enrolled for this study: 35 CFS patients, 35 patients relatives without CFS living with patients, and 35 healthy controls. The recruitment was performed according to the following inclusion criteria: CFS diagnosis according to Fukudas criteria, age between 18 to 80 years and signature of informed consent.
All participants who had used antibiotics, cortisone and non-steroidal anti-inflammatory drugs, inhibitors of proton pump inhibitors and probiotic drugs in the two months before the recruitment were excluded.
Healthy control subjects and patients relatives who had a previous history of diseases associated with chronic fatigue, bacterial and viral infections, cancer, chronic coronary diseases and allergies were also excluded.
Only the relatives who lived with the patients and shared similar dietary habits with them were enrolled. Age, sex and body mass index were matched in healthy controls.
Twenty-five patients reported gastrointestinal symptoms and showed post-exertional malaise. Moreover, eleven patients also had Irritable Bowel Syndrome diagnoses. Neither controls nor patients relatives reported this syndrome.
Chronic Fatigue Syndrome Linked With Differences In Gut Bacteria
26 April 17
People with chronic fatigue syndrome may have imbalances in their gut bacteria, a new study suggests.
The study found that people with chronic fatigue syndrome had higher levels of certain gut bacteria and lower levels of others compared to healthy people who didn’t have the condition.
The researchers then checked to see if these imbalances also characterized the subset of patients in the study who had irritable bowel syndrome , an intestinal disorder that is common in people with chronic fatigue syndrome. Results showed that patients did indeed have different patterns of gut bacteria disturbances depending on whether they had only chronic fatigue syndrome or both chronic fatigue syndrome and IBS.
The findings suggest that researchers may be able to divide chronic fatigue syndrome patients into different groups depending on their gut bacteria imbalances, which could aid in the diagnosis and treatment of the disease, the researchers said.
Chronic fatigue syndrome is a disorder in which people have extreme fatigue that is not improved by rest and is not the result of another medical condition. An estimated 35 percent to 90 percent of patients with chronic fatigue syndrome also report abdominal discomfort consistent with symptoms of IBS, the researchers said.
Future studies should look further into gastrointestinal symptoms and their relation to gut bacteria disturbances in people with chronic fatigue syndrome, the researchers said.
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Radionuclide Measurement Of Upper Gi Motility
Details and normal ranges of this double isotope test have been previously published . The solid meal consisted of 100 g of cooked ground beef containing 40MBq in-vivo labelled 99mTc-sulfur colloid-chicken liver, and the liquid meal consisted of 150 ml of 10% dextrose in water containing with 20 MBq of 67Ga-ethylenediaminetetraacetic acid . All medication was discontinued for 24 hours prior to each study. The test was performed at 10 am and monitored for at least two hours with the subject in the sitting position with the scintillation camera behind. The study commenced with a standardised oesophageal clearance study followed by eating the solid meal and then immediately drinking the glucose solution. Each study was continued for at least 2 hours. Oesophageal clearance was expressed as time to 95% clearance , Liquid gastric emptying as half-clearance time and solid emptying as amount remaining at 100 min .
The GI questionnaires were compared between CFS and control by Chi2, and Gastric emptying indices compared with historical normal range , and correlated with the mean symptom score .
The Study was approved by The Human Research Ethics Committee of the Royal Adelaide Hospital and informed consent given by the subjects.
Characteristics Of The Study Population
A total of 105 subjects: 35 patients and 70 control subjects were enrolled. The healthy control population constituted of two distinct groups: 35 patients relatives without CFS/ME and 35 healthy subjects not belonging to the patients families . Twenty-six CFS/ME patients were females and 9 were males, with a mean age of 46.4±16.1 years and a Body mass Index of 23.1±4.4. Twenty-five patients claimed gastrointestinal disturbances and 11 of them showed IBS comorbidity. The majority of patients suffered from post-exertional malaise. Patients relatives had a mean age of 54.4±15.9 years and a BMI of 25.5±5. Sixteen relatives were females and 19 males. The control group included 26 females and 9 males, with a mean age of 55.2±18 years and a BMI of 23.5±4.7. Seven patients relatives reported gastrointestinal symptoms, while only two relatives showed post-exertional malaise. No external controls and patients relatives reported IBS diagnosis. All participants were Caucasian, followed an omnivorous diet and belonged to the same geographical area . No one was a smoker. CFS subjects completed the Chalder Fatigue scale and the MOS SF-36 Health Survey .
Table 1 Characteristics of study population.
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Understanding Cfs And Gut Bacteria
Our analysis suggests that we may be able to subtype patients with ME/CFS by analyzing their fecal microbiome, says Brent L. Williams, co-lead investigator and assistant professor of pathology and cell biology at CII. Subtyping may provide clues to understanding differences in manifestations of disease.
Although a relationship between gut bacteria and the brain might seem to be a leap, there is growing evidence that there is, in fact, a great deal of communication between the two. Our guts send neuronal and hormonal signals to the brain. At the same time, gut bacteria produce myriad byproducts that have an influence on the gut itself.
Senior author W. Ian Lipkin explains: Much like IBS, ME/CFS may involve a breakdown in the bidirectional communication between the brain and the gut mediated by bacteria, their metabolites, and the molecules they influence.
The hope is that by probing the relationship between gut flora and CFS, we might gain more insight into a condition that has, so far, evaded our understanding. Lipton continues: By identifying the specific bacteria involved, we are one step closer to more accurate diagnosis and targeted therapies.
What Are The Signs & Symptoms Of Chronic Fatigue Syndrome
There’s a long list of possible symptoms that someone with chronic fatigue syndrome can have. The most common ones include:
- severe fatigue, which can make it hard to get out of bed and do normal daily activities
- sleep problems, such as trouble falling or staying asleep, or not having a refreshing sleep
- symptoms getting worse after physical or mental effort
- symptoms or dizziness that get worse after standing up or sitting upright from a lying down position
- problems with concentration and memory
- headaches and stomachaches
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The Gut Microbiome In Myalgic Encephalomyelitis /chronic Fatigue Syndrome
- 1Faculty of Medicine, University of Basel, Basel, Switzerland
- 2Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
- 3Division of Infectious Diseases and Hospital Epidemiology, Childrens Hospital of Eastern Switzerland, St. Gallen, Switzerland
- 4Charité – Universitätsmedizin Berlin, Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- 5Experimental and Clinical Research Center, A Joint Cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany
- 6Host-Microbiome Factors in Cardiovascular Disease, Max Delbruck Center for Molecular Medicine in the Helmholtz Association , Berlin, Germany
- 7Institute for Medical Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany
- 8European Molecular Biology Laboratory, Structural and Computational Biology Unit, Heidelberg, Germany
Link Between Chronic Fatigue Syndrome And Gut Bacteria Explored
Chronic fatigue syndrome is a poorly understood condition its exact causes are still not known. As medical researchers dig deeper, the potential involvement of gut bacteria is coming to the fore, revealing that the microbiome may play a significant role.
It was only in the 1980s that chronic fatigue syndrome finally received its official title, and since then, it has received a great deal attention.
Characterized by extreme fatigue that cannot be pinned to any underlying pathology, CFS remains a difficult condition to diagnose and treat.
Other symptoms include a loss of cognitive ability, sleep disturbances, enlarged lymph nodes, muscle pain, sore throat, and joint pain.
Also known as myalgic encephalomyelitis and, more recently, systemic exertion intolerance disease, the causes of CFS are still a mystery.
Some researchers believe that viral infections might be to blame, some point to psychological stressors, and others still think it could be hormonal or an immune system malfunction.
A new study, published in the journal Microbiome, asks whether gut bacteria may have a part to play. This connection might, at first glance, seem obscure. However, up to 90 percent of people with CFS also have irritable bowel syndrome , which makes a potential relationship easier to imagine.
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What Is The Outlook
CFS can last for years, but many conditions that cause fatigue are treatable. With treatment comes renewed energy. Your odds of regaining your energy depend greatly on how well you treat the cause of your fatigue.
GERD can be chronic, but its possible to control it with medications, a healthy lifestyle, and the avoidance of trigger foods and drinks. You can still enjoy a varied diet while avoiding the foods that cause symptoms.
Things No One Tells You About Chronic Fatigue Syndrome
Imagine feeling too exhausted to get out of bed, let alone go to work or spend time with your family. Now combine that kind of physical exhaustion with severe stomach pain, aching joints, and brain fog that makes it impossible to read a book or sustain a thought. Finally, imagine telling a doctor how you feel, and having him roll his eyes.
This is reality for many of those who suffer from the disease most know as “chronic fatigue syndrome.” There’s often little help or support available to them from the medical community or from friends and family.
“When you tell people how you feel, they say, ‘Well, I’m tired, too,'” says Carol Head, a recovered CFS sufferer and president of the Solve ME/CFS Initiativea charitable organization that funds medical research in pursuit of a cure for chronic fatigue.
Part of the problem, Head says, is that non-sufferers hear “fatigue” and think they understand what a CFS sufferer is going through. But they really don’t. “People who have endured both chemotherapy and ME/CFS say ME/CFS is even more debilitating, so ‘fatigue’ is not a good word for it,” she says.
The “ME” in ME/CFS stands for myalgic encephalomyelitisan alternate name Head and other sufferers prefer to chronic fatigue syndrome. “CFS is such a lightweight name,” she says. “The term ‘myalgic encephalomyelitis’ has actually been around longer, and it has the advantage of sounding like the serious, real disease that this is.”
It’s often debilitating.
It goes beyond chronic fatigue.
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What Is Irritable Bowel Syndrome
When you have IBS, your intestine does not function properly. The intestine itself is fine, but some people may have a lower pain tolerance when it comes to intestinal stretching and movement, or they could possibly have disordered intestinal muscle movement.
People with IBS can have urgent diarrhea or constipation or can have alternating bouts of each. They also have frequent abdominal pain. While most people with FMS don’t have abdominal pain related to digestion, IBS pain often feels similar to the pain of FMS.
Researchers don’t yet know why IBS develops, but they do know that it often starts after severe gastroenteritis or an extremely stressful event. Researchers currently are looking into what’s called the brain-gut connection in order to better understand the relationship between stress and IBS.
Sibo And Chronic Fatigue: The B12 Connection
One of the main hallmarks of SIBO is nutrient malabsorption. In particular, patients with SIBO typically contend with B12 deficiency. Normally, most of your gut bacteria live in your large intestine and colon, with only small amounts located in your small intestine. When you have SIBO, excess bacteria build up in your small intestine and bind to B12, preventing its absorption.1
Vitamin B12 is necessary for DNA synthesis and red blood cell production. Red blood cells carry oxygen throughout your body and help you stay energized. A low red blood cell count resulting from a B12 deficiency can cause feelings of weakness and fatigue.
SIBO leads to other nutrient deficiencies as well, and can even prevent the absorption of amino acids, proteins, and carbohydrates. Thats because when you have SIBO, nutrients from the food you eat never make it into your own cells. They are instead stolen by the bacteria to feed themselves. As I always say, Its not what you eat its what you digest and absorb. If you arent absorbing your food its no wonder you feel so sluggish and exhausted all the time!
The good news is, by managing your SIBO you can overcome chronic fatigue and reclaim your energy and vitality.
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Who Gets Chronic Fatigue Syndrome
Chronic fatigue syndrome can affect people of all ethnicities and ages, but is most common in people in their forties or fifties. It’s very rare in kids. A few teens do get CFS, and it affects more girls than guys.
Sometimes different people in the same family get CFS. This may be because the tendency to develop CFS is genetic.
Ways Sibo Wreaks Havoc On Your Body
1. Gas, bloating, and diarrhea2. Abdominal pain or cramping3. Constipation 4. Diagnosis of irritable bowel syndrome or inflammatory bowel disease 5. Food intolerances such as gluten, casein, lactose, fructose, and particularly histamine intolerance6. Chronic illnesses such as fibromyalgia, diabetes, neuromuscular disorders, and autoimmune diseases7. Fatigue8. Fat malabsorption 9. Rosacea and other skin rashes
Unsurprisingly, an imbalanced microbiome also plays a huge role in your energy levels. Lets take a look at the connection between a gut infection such as SIBO and chronic fatigue.
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Increased Gut Permeability And Bacterial Translocation In Me/cfs Patients
Another reason for increased intestinal permeability might come from the increased by-products of the amino acid fermentation to produce SCFA , as discussed below.
Bacterial translocation could also be important concerning PEM. Shukla and co-workers examined this connection in a small study by observing phenotype characteristics, post-exertion malaise and microbiome changes 15 minutes, 48 and 72 hours after a maximal exercise test. Besides the expected large changes in pain, fatigue and confusion, interestingly also the relative abundance of the intestinal microbiota changed differentially than in the control group. Following exercise, the genus Clostridium was increased in the blood fifteen minutes later and abundances of Bacilli were significantly higher 48 hours later, which might be due to increased post-exertional bacterial translocation. The authors also pointed out that researchers should rather focus on the post-exertional changes in intestinal composition, than on the dysbiosis itself .
Past Antibiotic Intake Hypothesis In Me/cfs Patients
It is well known that the postnatal and early life use of antibiotics disrupts the neonatal microbiome and is associated with a higher risk of several diseases such as asthma, IBD or type 2 diabetes . Also in adults there is, for example, an increased risk of 13% to develop diabetes after an antibiotic treatment , which supports that changes in the microbiome alter some metabolic conditions. According to a very large retrospective study, one treatment with antibiotics also increases the risk of developing IBD by 84% and with every following treatment there is a 6% higher risk. The researchers were also able to show that the earlier and more frequently antibiotics were taken, the higher was the risk of IBD . IBD is also often mentioned in connection with ME/CFS, although the correlation remains unclear . Interestingly, the mode of delivery influences the amount of antibiotic resistance genes in the microbiome, with vaginally delivered infants appearing to be relatively protected against antibiotic resistance . Berstad and co-workers suggested with their three-set dysbiotic march hypothesis an explanation for the high comorbidity in ME/CFS patients with IBS, as described above .
After the discovery of penicillin, antibiotics massively intruded into medical practice in the 1940s and 1960s . According to a recent report, antibiotics disrupt the bacterial composition in the gut for up to 4 years and to some extent permanently .
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What Is Chronic Fatigue Syndrome
Chronic fatigue syndrome is a complicated disease for doctors to diagnose and even fully understand.
CFS is a physical condition, but it can also affect a person psychologically. This means that someone with CFS may feel physical symptoms, such as being very tired and weak , headaches, or dizziness. But the person may also notice emotional symptoms, such as a loss of interest in favorite activities.
To make it even more complicated, different people with CFS can have different symptoms. And the symptoms of CFS often are similar those of other health conditions, like mono, Lyme disease, or depression. And the symptoms can vary over time, even in the same person.
This makes treating the illness complicated because no single medicine or treatment can address all the possible symptoms.