Chronic Fatigue Syndrome-Myalgic Encephalomyelitis (ME) is characterized by a severe, prolonged fatigue lasting for more than six months. Patients complain of extreme exhaustion; they tire easily in the course of normal activities, and may even be unable to perform normal tasks. Fatigue is accompanied by a number of other symptoms: neurocognitive impairments (memory loss, difficulty in concentrating), muscle pain, headaches, unrefreshing sleep, sore throat, persistent low grade fever, enlarged lymph nodes. ME shares overlapping symptomology with several diseases. Before making a diagnosis of ME, other specific illnesses in which fatigue is the core symptom (such as hypothyroidism, anemia, Lyme disease, lupus, diabetes, cancer...) must be excluded. The disease is also known as post-viral fatigue syndrome or chronic fatigue and immune dysfunction syndrome (CFIDS).

Prevalence and economical cost

ME affects between 0.2 and 0.5 percent of the population (approximately one million people affected in the USA, and two millions in Europe). Anybody can get ME, however women are affected more frequently than men by a ratio of 4:1. The most common age of onset is between 20 and 40 years. ME can also occur in children and adolescents. The annual socio-economic costs of ME (direct and indirect) have been estimated at $16 billion in the USA, and € 20 billion in Europe.

Intestinal dysfunctions in ME

Intestinal dysfunction is a characteristic of ME. A frequent disorder is dysbiosis, i.e. the overgrowth of pathogenic bacteria in the intestine. The adult human intestinal tract is estimated to contain up to 10exp14 viable microorganisms (10 times more than the number of cells that form the body!). Over 50 different genera of bacteria are represented, accounting for more than 500 different species... Intestinal microflora represents an ecosystem of the highest complexity. This microflora plays critical roles in the digestion and absorption of nutrients, in the synthesis of vitamins (B and K groups) and fatty acids, in the detoxification of ingested chemicals, but also in the regulation of the immune system.

Composition of the gut microflora can be affected by several factors including antibiotic use, stress, and diet. Alterations of the gut microflora may have serious consequences for the host health. Overgrown pathogenic bacteria produce toxins and compounds that are very detrimental to intestinal cells: for instance, sulfate-reducing bacteria produce toxic hydrogen sulfide.

Chronic inflammation of the gut mucosa, resulting from dysbiosis, can lead to the development of leaky gut syndrome. Leaky Gut Syndrome is a condition in which the ability of the intestinal wall to keep out large and undesirable molecules is reduced: substances that are normally kept within the intestines are "leaking" across the intestinal wall. One compound that can easily make its way to the blood is bacterial lipopolysaccharide (LPS). LPS will induce a strong pro-inflammatory response in monocytes and macrophages, involving recognition by a receptor (Toll-like receptor-4) and the subsequent secretion of cytokines such as IL-1, IL-6, TNF-alpha. Environmental toxins (food additives, pesticides, PCBs...) can also pass more easily into the circulation, and cause damage to all organs, notably the liver and the brain. Multiple Chemical Sensitivities may develop as the nervous system becomes sensitized. Finally, development of food allergies and auto-immune reactions may also occur, as undigested, large molecules which are allowed into the bloodstream will initiate a reaction of the immune system.

Opportunistic infections in ME

Dysregulations of the immune system in ME patients (depressed NK and T cells, chronic inflammation) favor the development of opportunistic infections such as mycoplasma, chlamydiae, or viral reactivations. Viruses frequently found in ME patients include herpesviruses (HHV-6, Epstein-Barr Virus, Cytomegalovirus) but also enteroviruses and parvovirus B19. All these viruses are found at high titers in the gastro-intestinal mucosa of the patients.