Abnormalities of AMPK Activation and Glucose Uptake in Cultured Skeletal Muscle Cells from Individuals with Chronic Fatigue Syndrome

Abstract Post exertional muscle fatigue is a key feature in Chronic Fatigue Syndrome (CFS). Abnormalities of skeletal muscle function have been identified in some but not all patients with CFS. To try to limit potential confounders that might contribute to this clinical heterogeneity, we developed a novel in vitro system that allows comparison of AMP…

Distinct plasma immune signatures in ME/CFS are present early in the course of illness

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may affect up to 4 million people in the United States alone. There are no validated laboratory tests for diagnosis or management despite global efforts to find biomarkers of disease. We considered the possibility that inability to identify such biomarkers reflected variations in diagnostic criteria and laboratory methods as well as the timing of sample collection during the course of the illness. Accordingly, we leveraged two large, multicenter cohort studies of ME/CFS to assess the relationship of immune signatures with diagnosis, illness duration, and other clinical variables. Controls were frequency-matched on key variables known to affect immune status, including season of sampling and geographic site, in addition to age and sex. We report here distinct alterations in plasma immune signatures early in the course of ME/CFS relative to healthy controls that are not present in subjects with longer duration of illness . Analyses based on disease duration revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as dissociation of intercytokine regulatory networks. We found a stronger correlation of cytokine alterations with illness duration than with measures of illness severity, suggesting that the immunopathology of ME/CFS is not static. These findings have critical implications for discovery of interventional strategies and early diagnosis of ME/CFS.

High-throughput 16S rRNA gene sequencing reveals alterations of intestinal microbiota in myalgic encephalomyelitis/chronic fatigue syndrome patients

43 Patients and 36 controls from Belgium and Norway were included in the study. Gut flora composition differed between people from different geographical origins. Significant alterations of gut microbiota composition were observed in patients.

This is relevant because 70% of all immune cells are located in the gastro-intestinal tract. Increased intestinal permeability may explain the systemic inflammatory situation in CFS.
Excess d-lactic acid production could contribute to mitochondrial dysfunction, but also to neurocognitive impairments in patients, since d-lactic acidosis is known to affect CNS function.

The predominance of women among patients, the fact that disease symptoms change upon e.g. puberty, pregnancy and menopause, has long suggested an involvement of hormones in ME/CFS. ER β, the preferred receptor of equol, is down-regulated in patients.
Disruption of estrogen signaling is consistent with some dysfunctions observed in ME/CFS. It could be related, for instance, with immune dysregulation since isoflavones, and more specifically equol, induce expression of antioxidant enzymes, and exert an anti-inflammatory action. Another potentially relevant aspect of phytoestrogens and their metabolites is their capacity to regulate vitamin D receptor activity, and vitamin D synthesis. The vitamin D system is critical for maintenance of gut mucosal immunity.Vitamin D has also been shown to modulate some processes that are critical for prevention of mucosal inflammation. One of the things not known yet is if the altered gut microbiota are cause or result of CFS.

Gut Inflammation in Chronic Fatigue Syndrome


Chronic fatigue syndrome (CFS) is a debilitating disease characterized by unexplained disabling fatigue and a combination of accompanying symptoms, the pathology of which is incompletely understood. Many CFS patients complain of gut dysfunction. In fact, patients with CFS are more likely to report a previous diagnosis of irritable bowel syndrome (IBS), a common functional disorder of the gut, and experience IBS related symptoms. Recently, evidence for interactions between the intestinal microbiota, mucosal barrier function, and the immune system have been shown to play a role in the disorder’s pathogenesis.

Studies examining the microecology of the gastrointestinal (GI) tract have identified specific microorganisms whose presence appears related to disease; in CFS, a role for altered intestinal microbiota in the pathogenesis of the disease has recently been suggested. Mucosal barrier dysfunction promoting bacterial translocation has also been observed. Finally, an altered mucosal immune system has been associated with the disease. In this article, we discuss the interplay between these factors in CFS and how they could play a significant role in GI dysfunction by modulating the activity of the enteric nervous system, the intrinsic innervation of the gut.

If an altered intestinal microbiota, mucosal barrier dysfunction, and aberrant intestinal immunity contribute to the pathogenesis of CFS, therapeutic efforts to modify gut microbiota could be a means to modulate the development and/or progression of this disorder. For example, the administration of probiotics could alter the gut microbiota, improve mucosal barrier function, decrease pro-inflammatory cytokines, and have the potential to positively influence mood in patients where both emotional symptoms and inflammatory immune signals are elevated. Probiotics also have the potential to improve gut motility, which is dysfunctional in many CFS patients.

Anxiogenic effect of subclinical bacterial infection in mice in the absence of overt immune activation

Gut pathogens can communicate with the CNS and influence emotional behaviors such as anxiety and depression, even at extremely low levels and in the absence of an immune response.
Mice were orally infected with Campylobacter jejuni and Citrobacter rodentium. The measured IL-6 and leukocytes showed no clear immune response to this infection, but the mice had altered levels of anxiety-like behavior. If you are depressed or have anxiety it could possibly help to alter your gut microbes and add pro/prebiotics to your diet.