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.