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.

In myalgic encephalomyelitis/chronic fatigue syndrome, increased autoimmune activity against 5-HT is associated with immuno-inflammatory pathways and bacterial translocation.

Positive autoimmune reactions against serotonin were significantly higher in CFIDS patients than controls.

Patients with serotonin( 5-HT ) autoimmune activity displayed higher TNFα, IL-1 and neopterin and increased IgA responses against LPS of commensal bacteria than those without 5-HT autoimmune activity. Anti-5-HT antibody positivity was significantly associated with increased scores on hyperalgesia, fatigue, neurocognitive and autonomic symptoms, sadness and a flu-like malaise.

Gut Inflammation in Chronic Fatigue Syndrome

Abstract

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.